GRAIL: Ganciclovir/Valganciclovir for Prevention of CMV Reactivation in Acute Injury of the Lung and Respiratory Failure

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01335932
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), Genentech, Inc. (Industry)
• Enrollment: 160
• Locations: 14
• Arms: 2
• Actual Duration (Months): 67.6
• Patients Per Site: 11.4
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To evaluate whether administration of ganciclovir reduces serum IL-6 levels (i.e. reduction between baseline and 14 days post-randomization) in immunocompetent adults with severe sepsis or trauma associated respiratory failure.

Primary Hypotheses:

• In CMV seropositive adults with severe sepsis or trauma , pulmonary and systemic CMV reactivation amplifies and perpetuates both lung and systemic inflammation mediated through specific cytokines, and contributes to pulmonary injury and multiorgan system failure,

AND

• Prevention of CMV reactivation with ganciclovir decreases pulmonary and systemic inflammatory cytokines that are important in the pathogenesis of sepsis and trauma related complications.

Condition or Disease	Intervention/Treatment	Phase
Acute Lung Injury; Acute Respiratory Distress Syndrome; Respiratory Failure	Drug: IV Ganciclovir; Drug: Placebo	Phase 2

Detailed Description

Critical illness due to severe sepsis and trauma are major causes of morbidity and mortality, and a substantial economic burden in the United States and worldwide. Despite advances in clinical care, patients with sepsis and trauma-associated respiratory failure represent specific populations with high rates of adverse outcomes. The etiology of respiratory failure in patients with severe sepsis and trauma is multifactorial, but acute lung injury (ALI) is one of the leading causes, and is associated with prolonged ICU and hospital stays, mortality, and long-term sequelae. Other than general supportive care, few specific interventions other than lung protective ventilation have been shown to improve outcomes in such patients. New approaches for understanding the pathogenesis and developing better therapies are urgently needed.

Acute Lung Injury (ALI) is a syndrome consisting of acute hypoxemic respiratory failure with bilateral pulmonary infiltrates that is associated with both pulmonary and nonpulmonary risk factors (eg. sepsis, trauma) and that is not due primarily to left atrial hypertension. Although a distinction between ALI and a more severe subtype (termed acute respiratory distress syndrome (ARDS) has been made, the pathogenesis, risk factors, and outcomes appear to be similar and for the purposes of this protocol, the term acute lung injury [ALI] will be used to encompass both entities. Accepted consensus definitions of ALI have been introduced and are now widely used for laboratory and clinical investigations of ALI. Acute Lung Injury (ALI) is defined as:

• PaO2/FiO2 <300

• Bilateral pulmonary infiltrates on chest x-ray

• Pulmonary Capillary Wedge Pressure <18mmHg or no clinical evidence of increased left atrial pressure Although a broad range of risk factors for ALI have been described, those that account for the majority of cases include: sepsis, pneumonia, trauma, and aspiration. It is well established that severe trauma is recognized as a precipitating cause of ALI. Recent studies have demonstrated that the incidence of acute lung injury (ALI) is much higher than previously thought, with an estimated age-adjusted incidence of 86 per 100,000 persons per year, resulting in an estimated ~190,000 cases annually in the US. The clinical and health care system impact of ALI is substantial, with an estimated 2,154,000 intensive care unit (ICU) days, 3,622,000 hospital days, and 75,000 deaths in 2000, and is expected to grow significantly given the marked age-related incidence and the aging population. Although general improvements in ICU care over the last 2 decades have led to a trend towards lower mortality due to certain ALI-associated risk factors (trauma, aspiration), the most common causes of ALI, sepsis and pneumonia, remain associated with high mortality rates of ~25-35%. Mortality in ALI is most commonly due to secondary infections/sepsis and multiorgan system failure rather than primary respiratory failure due to hypoxemia, highlighting the systemic nature of ALI. Even among initial survivors of ALI, substantial pulmonary and nonpulmonary functional impairment remains for months to years. Specifically, a proportion of those who survive the initial insult are at risk for prolonged mechanical ventilation and ICU/hospital stay, and the risk factors remain poorly defined. It has been hypothesized that a "2nd hit" may predispose certain patients to greater morbidity in this setting. Despite intensive basic and clinical investigation, only a single intervention (low-tidal volume ["lung protective"] ventilation) is generally accepted to decrease mortality in ALI, while multiple other strategies have failed to improve survival either in early clinical studies or definitive efficacy trials. Thus, given the high incidence and continued substantial clinical impact of ALI despite improvements in general medical/ICU care, and limited proven options other than lung-protective ventilation, new approaches to understanding the pathophysiology and identifying novel targets for intervention in ALI are a high priority.

Overly intense, persistent and dysregulated pulmonary and systemic inflammation has emerged as the leading hypothesis for the pathogenesis of ALI and its complications, but the contributory factors and mechanisms are incompletely defined. Several carefully-conducted prospective human studies have shown an association between specific inflammatory biomarkers in blood and BALF (both the initial levels at onset and changes over time) and important clinical outcomes in ALI. [Animal models have also demonstrated an association between inflammatory cytokines and non-pulmonary organ injury and dysfunction] In addition, one of the most important interventions (low-tidal volume ["lung protective"] ventilation) shown to decrease mortality in ALI is associated with reductions in inflammatory cytokines (IL-6, IL-8) in blood and bronchoalveolar lavage fluid [BALF].

Cytomegalovirus (CMV) is a ubiquitous virus in humans worldwide, and has been linked to adverse clinical outcomes including prolongation of mechanical ventilation, increased length of stay, and mortality in multiple studies of critically-ill, apparently immunocompetent, seropositive adults.

Cytomegalovirus (CMV) is a human herpes virus known to infect more than 50-90% of US adults and is known to be a major cause of morbidity and mortality in immunocompromised patients. CMV infection can be acquired through multiple means, including: mother-to-child (in utero, breast milk), infected body fluids (saliva, genital secretions), blood transfusion or organ transplant. The prevalence of CMV infection increases with age throughout life such that by age 90, ~90% of persons will have acquired CMV infection. In immunocompetent persons, following primary infection by any of the routes noted above, CMV is controlled by the immune system and establishes latency ("dormancy") in multiple organs/cell-types for the life of the host. In particular, the lung represents one of the largest reservoirs of latent CMV in seropositive hosts, and may explain the propensity for CMV-associated pulmonary disease in predisposed hosts. During periods of immunosuppression (or as a result of specific stimuli such as TNF-α, LPS, or catecholamines that are commonly associated with critical illness & sepsis [CMV can reactivate from latency (preferentially in the lung) to produce active infection (viral replication). In persons with impaired cellular immunity, reactivation can progress to high-grade CMV replication and commonly leads to tissue injury and clinically-evident disease such as CMV pneumonia. Lower-grade CMV reactivation that is otherwise clinically silent ("subclinical") can also be detected in apparently immunocompetent persons with critical illness using sensitive techniques such as PCR. In addition, even low-level, otherwise asymptomatic subclinical CMV reactivation can produce significant biologic effects both in vitro and in vivo, such as inflammation, fibrosis and immunosuppression. Each of these biologic effects of subclinical CMV infection has either previously been demonstrated (inflammation, fibrosis) or could theoretically be important (immunosuppression) in sepsis-associated ALI and its complications. These biological effects of CMV have been shown to occur through various mediators and other indirect means [Importantly, several important CMV-associated adverse clinical outcomes in transplant populations [allograft rejection, secondary infections] are not necessarily accompanied by overt CMV disease and can only be detected by relatively sensitive means of virus detection such as PCR.

Reactivation of CMV in apparently immunocompetent patients with critical illness due to a broad range of causes has been documented in multiple prior studies using a variety of virologic techniques. The specific triggers for CMV reactivation from latency have been identified and are known to be elevated in patients with sepsis and acute lung injury [A prospective study in intubated patients with sepsis from Germany reported more than 60% rate of CMV DNA detection in tracheal aspirates.

In addition to CMV reactivation in sepsis, CMV reactivation has also been demonstrated specifically in lung and blood of patients with acute lung injury.

Retrospectively testing samples collected in a prospective observational cohort study of patients at risk of developing ARDS, CMV reactivation (ie. CMV DNA by PCR) was detected in BALF and/or plasma of 2/5 [40%] of subjects who developed ARDS, in sequential samples from 7/20 [35%] patients with ARDS, but not in patients at risk but who did not develop ARDS (0/5) [Limaye 2009 unpublished data]. In a separate study, CMV reactivation was retrospectively assessed by PCR in BALF of 88 subjects enrolled in a randomized trial of fish oil for treatment of ALI. Seropositivity at baseline (ie. evidence of latent CMV infection) in the cohort was 65% (similar to prior age-related estimates), and CMV reactivation (ie. CMV DNA by PCR) was detected in BALF of 12/57 [21%] patients [Limaye unpublished data 2009].

Several lines of evidence have linked CMV reactivation with adverse clinical outcomes in non-immunosuppressed adults with critical illness. In a recent meta-analysis, CMV reactivation (compared to no reactivation) was associated with a 2-fold increased odds of mortality in ICU patients.

In addition to mortality, recent studies have demonstrated a strong and independent association between CMV reactivation and increased hospital and ICU length of stay and duration of mechanical ventilation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Randomized Double-Blind Placebo-Controlled Trial of Ganciclovir/Valganciclovir for Prevention of Cytomegalovirus Reactivation in Acute Injury of the Lung and Respiratory Failure (The GRAIL Study)
• Actual Study Start Date: Mar 10, 2011
• Actual Primary Completion Date: Jun 17, 2016
• Actual Study Completion Date: Oct 28, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: IV Ganciclovir 5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge	Drug: IV Ganciclovir; For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.
Placebo Comparator: Placebo normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge	Drug: Placebo; For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.

Outcome Measures

Primary Outcome Measures

1. Serum IL-6 Level [Baseline and Day 14]

   Change between baseline and 14 days post-randomization between placebo & ganciclovir groups

Secondary Outcome Measures

1. Number of Participants With CMV Reactivation at 28 Days in Plasma [at 28 days post-randomization]

   Number of participants in baseline negatives with CMV reactivation at any level at day 28

2. BAL Levels of IL-6 [at 7 days post-randomization]

   Levels of IL-6 from BALs at 7 days post-randomization

3. Number of Participants With Organ System Failure at 14 Days [at 14 days post-randomization]

   Number of participants experiencing organ system failure at 14 days

4. Number of Days Alive and Not in the ICU [by 28 days post-randomization]

   Number of ICU days alive and not in the ICU by day 28

5. CMV Disease [by 180 days post-randomization]

   Need to be biopsy-proven

6. Grade 3 AEs or Higher [by 35 days post-randomization]

   Number of patients with greater than one AE of grade 3 or more

7. SF-36 Health Survey [at 1 day post-randomization]

   Physical Component Summary of SF-36. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability.

8. Incidence of CMV Reactivation >1,000 IU Per mL at Day 28 in Plasma [at 28 days post-randomization]

   Number of participants with CMV reactivation >1,000 IU per mL at day 28 in plasma

9. Incidence of CMV Reactivation at Any Level at 28 Days in Throat [at 28 days post-randomization]

   CMV reactivation in baseline negatives at any level at day 28 in throat

10. Incidence of CMV Reactivation >1,000 IU Per mL at 28 Days in Throat [at 28 days post-randomization]

    Number of participants with CMV reactivation >1,000 IU per mL at day 28 in throat

11. CMV AUC in Blood [Day 0 to 28 days post-randomization]

    CMV AUC in blood from day 0 to day 28

12. CMV AUC in Throat [Day 0 to 28 days post-randomization]

    CMV AUC in Throat from day 0 to day 28

13. CMV Peak Viral Load in Blood [at 28 days post-randomization]

    CMV Peak Viremia in blood at day 28

14. BAL Levels of IL-8 [at 7 days post-randomization]

    Levels of IL-8 in BALs at day 7

15. BAL Levels of TNFa [at 7 days post-randomization]

    Levels of TNFa in BALs at day 7

16. Plasma Levels of IL-6 [at 7 days post-randomization]

    Plasma levels of IL-6.

17. Plasma Levels of IL-8 [at 7 days post-randomization]

    Levels of IL-8 in plasma at day 7

18. Plasma Levels of TNF a [at 7 days post-randomization]

    Plasma levels of TNF a at day 7.Cytokines are summarized on log 10 scale. When logged value is negative, the raw value would be less than 1.

19. Plasma Levels of TNF a [Day 0 to 28 days post-randomization]

    Plasma levels of TNF a from day 0 to day 28

20. Plasma Levels of IL-6 [at 28 days post-randomization]

    Plasma levels of IL-6 at day 28

21. Plasma Levels of IL-8 [at 28 days post-randomization]

    Plasma levels of IL-8 at day 28

22. Plasma Levels of Soluble ICAM-1 [at 28 days post-randomization]

    Plasma levels of soluble ICAM-1 at day 28

23. Plasma Levels of Soluble ICAM-1 [at 7 days post-randomization]

    Plasma levels of soluble ICAM-1 at day 7

24. Peak Plasma Levels of Soluble ICAM-1 [Day 0 to 28 days post-randomization]

    Peak Plasma levels of soluble ICAM-1 from day 0 to day 28

25. Peak Plasma Levels of TNF-a [at 28 days post-randomization]

    Peak Plasma levels of TNF-a at day 28

26. Peak Plasma Levels of IL-10 [at 28 days post-randomization]

    Peak Plasma levels of IL-10 at day 28

27. Peak Plasma Levels of IL-8 [at 28 days post-randomization]

    Peak Plasma levels of IL-8 at day 28

28. Peak Plasma Levels of IL-6 [at 28 days post-randomization]

    Peak Plasma levels of IL-6 at day 28

29. AUC Plasma Levels of IL-6 [Day 0 to 28 days post-randomization]

    AUC Plasma levels of IL-6 from day 0 to day 28

30. AUC Plasma Levels of IL-8 [Day 0 to 28 days post-randomization]

    AUC Plasma levels of IL-8 from day 0 to day 28

31. AUC Plasma Levels of IL-10 [at 28 days post-randomization]

    AUC Plasma levels of IL-10 from day 0 to day 28

32. AUC Plasma Levels of TNF-a [at 28 days post-randomization]

    AUC Plasma levels of TNF-a from day 0 to day 28

33. AUC Plasma Levels of Soluble ICAM-1 [at 28 days post-randomization]

    AUC Plasma levels of soluble ICAM-1 from day 0 to day 28

34. Length of Stay [by 180 days post-randomization]

    Hospital days alive and not hospitalized by day 180

35. Length of Stay [by 28 days post-randomization]

    Hospital days alive and not hospitalized by day 28

36. Organ System Failure at 28 Days [at 28 days post-randomization]

    Number of participants with organ system failure at 28 days

37. Duration of Mechanical Ventilation as Assessed by Ventilator Free Days [at 28 days post-randomization]

    Number of days of mechanical ventilation duration as assessed by ventilator free days

38. Duration of Mechanical Ventilation as Assessed by Ventilator Days [at 28 days post-randomization]

    Number of days of mechanical ventilation duration as assessed by ventilator days

39. Bacteremia and/or Fungemia [at 28 days post-randomization]

    Number of participants with bacteremia and/or fungemia

40. Mortality [at 60 days post-randomization]

    Mortality at 60 days post randomization

41. Mortality at 180 Days [at 180 days post-randomization]

    Mortality at 180 days post-randomization

42. SF-36 Functional Assessment Physical Component [at 180 days post-randomization]

    Physical Component Summary at 180 days post- randomization. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability

43. SF-36 Functional Assessment Mental Component [at 180 days post-randomization]

    Mental Component Summary at 180 days post-randomization. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability

44. SF-36 Functional Assessment Mental Component on Day 1 [at 1 day post-randomization]

    SF-36 Mental Component Summary at 1 day post-randomization. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability

45. Patients With Serious Adverse Events [by 35 days post-randomization]

    Number of patients with Serious Adverse Events by day 35

46. Time to Neutropenia [by 35 days post-randomization]

    Time to neutropenia by 35 days post-randomization

47. Use of Granulocyte-colony Stimulating Factor [by 35 days post-randomization]

    Number of participants requiring Granulocyte-colony stimulating factor

48. Renal Insufficiency [by 35 days post-randomization]

    Number of patients experiencing a glomerular filtration rate < 60mL/min at day 35

49. Red Blood Cell Transfusions Required Per Patients [by 35 days post-randomization]

    Red blood cell transfusions required per patients by day 35

50. Platelet Transfusions [by 35 days post-randomization]

    Platelet transfusions per patient

51. Clinical Outcomes [at 14 days post-randomization]

    Composite of survival status and >7 days ventilation status, and IL-6 levels. In the composite analysis, the endpoint is composed by death, ventilation status and change of cytokine.

52. Bacteremia and Fungemia Outcomes [at 7 days post-randomization]

    Bacteremia and fungemia outcomes among subjects who survive at least 7 days

53. Bacteremia and Fungemia Outcomes in Mechanically Ventilated Subjets [at 7 through 14 days post-randomization]

    Bacteremia and fungemia events among subjects who are mechanically ventilated for at least 7 through 14 days after randomization

54. Overall Mortality [at 7 days post-randomization]

    Overall mortality amongst subjects who survive at least 7 days after randomization

55. Number of Mechanical Ventilated Days [at 7 days post-randomization]

    Number of mechanical ventilated days amongst subjects who survive at least 7 days after randomization

56. Number of Ventilator-free Days [at 7 days post-randomization]

    Number of ventilator-free days amongst subjects who survive at least 7 days after randomization

57. Number of Days in the ICU [at 7 days post-randomization]

    Number of days in the ICU amongst subjects who survive at least 7 days after randomization

58. Number of ICU-free Days [at 7 days post-randomization]

    Number of ICU-free days amongst subjects who survive at least 7 days after randomization

59. Number of Days in the Hospital [at 7 days post-randomization]

    Number of days in the hospital amongst subjects who survive at least 7 days after randomization

60. Number of Hospital-free Days [at 7 days post-randomization]

    Number of hospital-free days amongst subjects who survive at least 7 days after randomization

61. Mortality Among Subjects Mechanically Ventilated From Day 7 to 14 [28 days]

    Mortality among subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization

62. Number of Mechanically Ventilated Days Among Subjects by Day 28 [28 days]

    Number of mechanically ventilated days among subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization

63. Number of Ventilator-free Days Among Subjects by Day 28 [28 days]

    Number of ventilator-free days among subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization

64. Number of Days in ICU Amongst Subjects by Day 28 [28 days]

    Number of days in ICU amongst subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization

65. Number of ICU-free Days Amongst Subjects by Day 28 [28 days]

    Number of ICU-free days amongst subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization

66. Number of Hospital-free Days Among Subjects by Day 28 [28 days]

    Number of hospital-free days among subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subject/next of kin informed consent

2. Age >= 18 years

3. CMV IgG seropositive. The following tests are acceptable:

• FDA licensed test in a local lab approved by the coordinating center (FHCRC, Seattle, WA).

• Test in central study lab (ARUP, Salt Lake City, UT)

• A report that patient has previously been tested and found to be CMV seropositive at any time (a credible next of kin report is acceptable; confirmatory test will be done but results are not required for randomization)

1. Intubated and requiring mechanical positive pressure ventilation (including Acute Lung Injury/ARDS (EA Consensus Definition))

2. Meets criteria for either:

3. Severe sepsis criteria (as defined in appendix G) within a 24-hour time period within the 120 hour window

OR

1. Trauma with respiratory failure and an ISS score > 15 within a 24 hour time period, and within the 120 hour window (where mechanical ventilation is not due solely to a head injury)

2. On the day of randomization (by local criteria):

• Not eligible for SBT (use of sedation and/or vasopressor does not specifically contraindicate SBT),or

• Failed SBT

Exclusion Criteria:

1. BMI > 60 (1st weight during hospital admission)

2. Known or suspected immunosuppression, including:

• HIV+ (i.e. prior positive test or clinical signs of suspicion of HIV/AIDS; a negative HIV test is not required for enrollment)

• stem cell transplantation:

• within 6 months after autologous transplantation or

• within 1 years after allogeneic transplantation (regardless of immunosuppression)

• greater than 1 year of allogeneic transplantation if still taking systemic immunosuppression or prophylactic antibiotics (e.g. for chronic graft versus host disease)

Note: if details of stem cell transplantation are unknown, patients who do not take systemic immunosuppression and do not take anti-infective prophylaxis are acceptable for enrollment and randomization.

• solid organ transplantation with receipt of systemic immunosuppression (any time).

• cytotoxic anti-cancer chemotherapy within the past three months (Note: next-of-kin estimate is acceptable).

• congenital immunodeficiency requiring antimicrobial prophylaxis (e.g. TMP-SMX, dapsone, antifungal drugs, intravenous immunoglobulin).

• receipt of one or more of the following in the indicated time period:

• within 6 months: alemtuzumab, antithymocyte/antilymphocyte antibodies

• within 3 months: immunomodulator therapy (TNF-alpha antagonist, rituximab, tocilizumab, IL1 receptor antagonist and other biologics)

• within 30 days:

• corticosteroids > 10 mg/day (chronic administration, daily average over the time period)

• topical steroids are permissible

• use of hydrocortisone in "stress doses" up to 100 mg four times a day (400mg/daily) for up to 4 days prior to randomization is permissible

• use of temporary short-term (up to 2 weeks) increased doses of systemic steroids (up tp 1 mg/kg) for exacerbation of chronic conditions are permissible.

• methotrexate (> 10.0 mg/week)

• azathioprine (> 75 mg/day)

Note: if no information on these agents is available in the history and no direct or indirect evidence exists from the history that any condition exists that requires treatment with these agents (based on the investigator's assessment), the subject may be enrolled. For all drug information, next-of-kin estimates are acceptable. See Appendix D for commonly prescribed immunosuppressive agents.

1. Expected to survive < 72 hours (in the opinion of the investigator)

2. Has been hospitalized for > 120 hours (subjects who are transferred from a chronic care ward, such as a rehabilitation unit, with an acute event are acceptable).

3. Pregnant or breastfeeding (either currently or expected within one month).

Note: for women of childbearing age (18-60 years, unless documentation of surgical sterilization [hysterectomy, tubal ligation, oophorectomy]), if a pregnancy test has not been done as part of initial ICU admission work-up, it will be ordered stat and documented to be negative before randomization. Both urine and blood tests are acceptable.

1. Absolute neutrophil count < 1,000/mm3 (if no ANC value is available, the WBC must be > 2500/mm3)

2. Use of cidofovir within seven (7) days of patient randomization. The use of the following antivirals is permitted under the following conditions:

• Ganciclovir, foscarnet, high-dose acyclovir, or valacyclovir until the day of randomization

• Acyclovir as empiric therapy for central nervous system HSV or VZV infection until the diagnosis can be excluded

• For enrolled patients during the active study drug phase, acyclovir, famciclovir, valacyclovir for treatment of HSV or VZV infection as clinically indicated.

1. Currently enrolled in an interventional trial of an investigational therapeutic agent known or suspected to have anti-CMV activity, or to be associated with significant known hematologic toxicity (Note: confirm eligibility with one of the study medical directors at the coordinating site).

2. At baseline patients who have both a tracheostomy, and have been on continuous 24-hour chronic mechanical ventilation.

3. Patients with Child Class C Cirrhosis.

4. Patients with pre-existing interstitial lung disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado / National Jewish Health / Swedish Medical Center	Denver	Colorado	United States	80206
2	Northwestern University	Chicago	Illinois	United States	60611
3	Baystate Critical Care Medicine / Tufts University School of Medicine	Springfield	Massachusetts	United States	01199
4	University of Michigan	Ann Arbor	Michigan	United States	48109-5360
5	Wakeforest University, School of Medicine	Winston-Salem	North Carolina	United States	27157
6	The Cleveland Clinic Foundation	Cleveland	Ohio	United States	44195
7	Ohio State University Medical Center	Columbus	Ohio	United States	43210
8	The Oregon Clinic	Portland	Oregon	United States	97220
9	University of Pennsylvania Medical Center	Philadelphia	Pennsylvania	United States	19104-6160
10	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15261
11	University of Vermont College of Medicine	Burlington	Vermont	United States	05405
12	University of Virginia	Charlottesville	Virginia	United States	22908-0546
13	Harborview Medical Center	Seattle	Washington	United States	98104
14	University of Washington Medical Center / Harborview Medical Center	Seattle	Washington	United States	98195

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Heart, Lung, and Blood Institute (NHLBI)
• Genentech, Inc.

Investigators

• Principal Investigator: Michael Boeckh, MD, Fred Hutchinson Cancer Center
• Principal Investigator: Ajit Limaye, MD, University of Washington
• Study Director: Louise Kimball, PhD, RN, Fred Hutchinson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Michael Boeckh, Principal Investigator, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT01335932
• Other Study ID Numbers: 7217; U01HL102547
• First Posted: Apr 15, 2011
• Last Update Posted: Aug 21, 2018
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Michael Boeckh, Principal Investigator, Fred Hutchinson Cancer Center: Acute Lung Injury; Acute Respiratory Distress Syndrome; Respiratory Failure; Cytomegalovirus seropositive; Infection; Intravenous Ganciclovir; Non-immunocompromised; Valganciclovir
• Additional relevant MeSH terms: Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Respiratory Insufficiency; Acute Lung Injury; Lung Injury; Wounds and Injuries; Ganciclovir; Ganciclovir triphosphate

Study Results

Participant Flow

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Period Title: Overall Study
STARTED	84	76
COMPLETED	84	72
NOT COMPLETED	0	4

Baseline Characteristics

Arm/Group Title	IV Ganciclovir	Placebo	Total
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.	Total of all reporting groups
Overall Participants	84	76	160
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	55.2	58.2	56.6
Sex: Female, Male (Count of Participants)
Female	35 41.7%	36 47.4%	71 44.4%
Male	49 58.3%	40 52.6%	89 55.6%
Region of Enrollment (participants) [Number]
United States	84 100%	76 100%	160 100%

Outcome Measures

1. Primary Outcome

Title	Serum IL-6 Level
Description	Change between baseline and 14 days post-randomization between placebo & ganciclovir groups
Time Frame	Baseline and Day 14

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Mean (Standard Deviation) [pg/mL]	-0.79 (0.65)	-0.79 (0.69)

2. Secondary Outcome

Title	Number of Participants With CMV Reactivation at 28 Days in Plasma
Description	Number of participants in baseline negatives with CMV reactivation at any level at day 28
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	77	67
CMV viremia at any level	3 3.6%	23 30.3%
no CMV viremia at any level	74 88.1%	44 57.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	.0001
	Comments
	Method	Fisher Exact
	Comments

3. Secondary Outcome

Title	BAL Levels of IL-6
Description	Levels of IL-6 from BALs at 7 days post-randomization
Time Frame	at 7 days post-randomization

Outcome Measure Data

Analysis Population Description

The protocol was modified to remove the inclusion of BALs, thus these numbers reflect the total BALs performed prior to the modification.

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	3	7
Mean (Standard Deviation) [log 10 pg/mL]	1.01 (0.78)	1.66 (1.26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Number of Participants With Organ System Failure at 14 Days
Description	Number of participants experiencing organ system failure at 14 days
Time Frame	at 14 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
with organ failure	0 0%	2 2.6%
without organ failure	84 100%	70 92.1%

5. Secondary Outcome

Title	Number of Days Alive and Not in the ICU
Description	Number of ICU days alive and not in the ICU by day 28
Time Frame	by 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Mean (Standard Deviation) [days]	10.02 (6.84)	10.97 (8.23)

6. Secondary Outcome

Title	CMV Disease
Description	Need to be biopsy-proven
Time Frame	by 180 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Biopsy proven CMV disease	0 0%	0 0%
No Biopsy proven CMV disease	84 100%	72 94.7%

7. Secondary Outcome

Title	Grade 3 AEs or Higher
Description	Number of patients with greater than one AE of grade 3 or more
Time Frame	by 35 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
number with AE greater than grade 3	11 13.1%	10 13.2%
number without AE greater than grade 3	73 86.9%	62 81.6%

8. Secondary Outcome

Title	SF-36 Health Survey
Description	Physical Component Summary of SF-36. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability.
Time Frame	at 1 day post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	53	35
Mean (Standard Deviation) [scores on a scale]	36.37 (10.93)	35 (11.28)

9. Secondary Outcome

Title	Incidence of CMV Reactivation >1,000 IU Per mL at Day 28 in Plasma
Description	Number of participants with CMV reactivation >1,000 IU per mL at day 28 in plasma
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	77	67
CMV viremia >1,000 copies per mL	0 0%	5 6.6%
No CMV viremia >1,000 copies per mL	77 91.7%	62 81.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	Fisher Exact
	Comments

10. Secondary Outcome

Title	Incidence of CMV Reactivation at Any Level at 28 Days in Throat
Description	CMV reactivation in baseline negatives at any level at day 28 in throat
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	80	67
CMV reactivation at any level at day 28 in throat	2 2.4%	6 7.9%
No CMV reactivation at any level at day 28in throa	78 92.9%	61 80.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	Fisher Exact
	Comments

11. Secondary Outcome

Title	Incidence of CMV Reactivation >1,000 IU Per mL at 28 Days in Throat
Description	Number of participants with CMV reactivation >1,000 IU per mL at day 28 in throat
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	80	67
CMV reactivation >1,000 in IU per mL	0 0%	1 1.3%
No CMV reactivation >1,000 IU per mL in throat	80 95.2%	66 86.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.10
	Comments
	Method	Fisher Exact
	Comments

12. Secondary Outcome

Title	CMV AUC in Blood
Description	CMV AUC in blood from day 0 to day 28
Time Frame	Day 0 to 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Mean (Standard Deviation) [IU*day/mL]	0.11 (0.39)	0.39 (0.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	t-test, 2 sided
	Comments

13. Secondary Outcome

Title	CMV AUC in Throat
Description	CMV AUC in Throat from day 0 to day 28
Time Frame	Day 0 to 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Mean (Standard Deviation) [IU*day/mL]	0.03 (0.14)	0.17 (0.52)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.03
	Comments
	Method	t-test, 2 sided
	Comments

14. Secondary Outcome

Title	CMV Peak Viral Load in Blood
Description	CMV Peak Viremia in blood at day 28
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Mean (Standard Deviation) [log 10 IU/mL]	0.24 (0.67)	0.89 (1.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	t-test, 2 sided
	Comments

15. Secondary Outcome

Title	BAL Levels of IL-8
Description	Levels of IL-8 in BALs at day 7
Time Frame	at 7 days post-randomization

Outcome Measure Data

Analysis Population Description

The protocol was modified to remove the inclusion of BALs, thus these numbers reflect the total BALs performed prior to the modification.

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	3	7
Mean (Standard Deviation) [log 10 pg/mL]	2.21 (0.66)	2.61 (1.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.73
	Comments
	Method	t-test, 2 sided
	Comments

16. Secondary Outcome

Title	BAL Levels of TNFa
Description	Levels of TNFa in BALs at day 7
Time Frame	at 7 days post-randomization

Outcome Measure Data

Analysis Population Description

The protocol was modified to remove the inclusion of BALs, thus these numbers reflect the total BALs performed prior to the modification.

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	3	7
Mean (Standard Deviation) [log 10 pg/mL]	0.18 (0)	0.46 (0.49)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments
	Method	t-test, 2 sided
	Comments

17. Secondary Outcome

Title	Plasma Levels of IL-6
Description	Plasma levels of IL-6.
Time Frame	at 7 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	75	57
Mean (Standard Deviation) [log 10 pg/mL]	0.87 (0.84)	0.92 (0.62)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.31
	Comments
	Method	t-test, 2 sided
	Comments

18. Secondary Outcome

Title	Plasma Levels of IL-8
Description	Levels of IL-8 in plasma at day 7
Time Frame	at 7 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	75	57
Mean (Standard Deviation) [log 10 pg/mL]	1.38 (0.6)	1.38 (0.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.96
	Comments
	Method	t-test, 2 sided
	Comments

19. Secondary Outcome

Title	Plasma Levels of TNF a
Description	Plasma levels of TNF a at day 7.Cytokines are summarized on log 10 scale. When logged value is negative, the raw value would be less than 1.
Time Frame	at 7 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	75	57
Mean (Standard Deviation) [log 10 pg/mL]	-0.07 (0.36)	-0.1 (0.35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.63
	Comments
	Method	t-test, 2 sided
	Comments

20. Secondary Outcome

Title	Plasma Levels of TNF a
Description	Plasma levels of TNF a from day 0 to day 28
Time Frame	Day 0 to 28 days post-randomization

Outcome Measure Data

Analysis Population Description

Cytokines are summarized on a log 10 scale. When the logged value is negative, the raw value would be less than 1.

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	33	31
Mean (Standard Deviation) [log 10 pg/mL]	-0.06 (0.37)	-0.11 (0.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.51
	Comments
	Method	t-test, 2 sided
	Comments

21. Secondary Outcome

Title	Plasma Levels of IL-6
Description	Plasma levels of IL-6 at day 28
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	33	31
Mean (Standard Deviation) [log 10 pg/mL]	0.35 (0.51)	0.59 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	t-test, 2 sided
	Comments

22. Secondary Outcome

Title	Plasma Levels of IL-8
Description	Plasma levels of IL-8 at day 28
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	33	31
Mean (Standard Deviation) [log 10 pg/mL]	1.09 (0.46)	1.27 (0.46)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	t-test, 2 sided
	Comments

23. Secondary Outcome

Title	Plasma Levels of Soluble ICAM-1
Description	Plasma levels of soluble ICAM-1 at day 28
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	33	31
Mean (Standard Deviation) [log 10 pg/mL]	5.34 (0.19)	5.48 (0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	t-test, 2 sided
	Comments

24. Secondary Outcome

Title	Plasma Levels of Soluble ICAM-1
Description	Plasma levels of soluble ICAM-1 at day 7
Time Frame	at 7 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	75	57
Mean (Standard Deviation) [log 10 pg/mL]	5.43 (0.21)	5.45 (0.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.64
	Comments
	Method	t-test, 2 sided
	Comments

25. Secondary Outcome

Title	Peak Plasma Levels of Soluble ICAM-1
Description	Peak Plasma levels of soluble ICAM-1 from day 0 to day 28
Time Frame	Day 0 to 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Mean (Standard Deviation) [log 10 pg/mL]	5.52 (0.2)	5.57 (0.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.24
	Comments
	Method	t-test, 2 sided
	Comments

26. Secondary Outcome

Title	Peak Plasma Levels of TNF-a
Description	Peak Plasma levels of TNF-a at day 28
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Mean (Standard Deviation) [log 10 pg/mL]	0.16 (0.3)	0.17 (0.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.76
	Comments
	Method	t-test, 2 sided
	Comments

27. Secondary Outcome

Title	Peak Plasma Levels of IL-10
Description	Peak Plasma levels of IL-10 at day 28
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Mean (Standard Deviation) [log 10 pg/mL]	0.88 (0.52)	0.82 (0.49)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.45
	Comments
	Method	t-test, 2 sided
	Comments

28. Secondary Outcome

Title	Peak Plasma Levels of IL-8
Description	Peak Plasma levels of IL-8 at day 28
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Mean (Standard Deviation) [log 10 pg/mL]	1.67 (0.65)	1.66 (0.44)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.92
	Comments
	Method	t-test, 2 sided
	Comments

29. Secondary Outcome

Title	Peak Plasma Levels of IL-6
Description	Peak Plasma levels of IL-6 at day 28
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Mean (Standard Deviation) [log 10 pg/mL]	1.57 (0.78)	1.56 (0.78)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.94
	Comments
	Method	t-test, 2 sided
	Comments

30. Secondary Outcome

Title	AUC Plasma Levels of IL-6
Description	AUC Plasma levels of IL-6 from day 0 to day 28
Time Frame	Day 0 to 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Mean (Standard Deviation) [IU*day/mL]	0.68 (0.49)	0.75 (0.51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.37
	Comments
	Method	t-test, 2 sided
	Comments

31. Secondary Outcome

Title	AUC Plasma Levels of IL-8
Description	AUC Plasma levels of IL-8 from day 0 to day 28
Time Frame	Day 0 to 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Mean (Standard Deviation) [IU*day/mL]	1.15 (0.45)	1.13 (0.42)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.80
	Comments
	Method	t-test, 2 sided
	Comments

32. Secondary Outcome

Title	AUC Plasma Levels of IL-10
Description	AUC Plasma levels of IL-10 from day 0 to day 28
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Mean (Standard Deviation) [IU*day/mL]	0.36 (0.36)	0.35 (0.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.93
	Comments
	Method	t-test, 2 sided
	Comments

33. Secondary Outcome

Title	AUC Plasma Levels of TNF-a
Description	AUC Plasma levels of TNF-a from day 0 to day 28
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Mean (Standard Deviation) [IU*day/mL]	-0.14 (0.28)	-0.14 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.93
	Comments
	Method	t-test, 2 sided
	Comments

34. Secondary Outcome

Title	AUC Plasma Levels of Soluble ICAM-1
Description	AUC Plasma levels of soluble ICAM-1 from day 0 to day 28
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Mean (Standard Deviation) [IU*day/mL]	4.78 (0.98)	4.65 (1.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	IV Ganciclovir, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.45
	Comments
	Method	t-test, 2 sided
	Comments

35. Secondary Outcome

Title	Length of Stay
Description	Hospital days alive and not hospitalized by day 180
Time Frame	by 180 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	55	47
Mean (Standard Deviation) [days]	145.13 (47.63)	145.94 (47.88)

36. Secondary Outcome

Title	Length of Stay
Description	Hospital days alive and not hospitalized by day 28
Time Frame	by 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	78	69
Mean (Standard Deviation) [days]	9.96 (8.52)	8.72 (8.24)

37. Secondary Outcome

Title	Organ System Failure at 28 Days
Description	Number of participants with organ system failure at 28 days
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
with organ failure	0 0%	2 2.6%
without organ failure	84 100%	70 92.1%

38. Secondary Outcome

Title	Duration of Mechanical Ventilation as Assessed by Ventilator Free Days
Description	Number of days of mechanical ventilation duration as assessed by ventilator free days
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Mean (Standard Deviation) [days]	18.71 (9.08)	15.97 (9.72)

39. Secondary Outcome

Title	Duration of Mechanical Ventilation as Assessed by Ventilator Days
Description	Number of days of mechanical ventilation duration as assessed by ventilator days
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Mean (Standard Deviation) [days]	6.95 (6.16)	8.5 (7.17)

40. Secondary Outcome

Title	Bacteremia and/or Fungemia
Description	Number of participants with bacteremia and/or fungemia
Time Frame	at 28 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
with bacteremia and /or fungemia	15 17.9%	11 14.5%
without bacteremia and /or fungemia	69 82.1%	61 80.3%

41. Secondary Outcome

Title	Mortality
Description	Mortality at 60 days post randomization
Time Frame	at 60 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
dead	13 15.5%	12 15.8%
alive	71 84.5%	60 78.9%

42. Secondary Outcome

Title	Mortality at 180 Days
Description	Mortality at 180 days post-randomization
Time Frame	at 180 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
dead	18 21.4%	19 25%
alive	66 78.6%	53 69.7%

43. Secondary Outcome

Title	SF-36 Functional Assessment Physical Component
Description	Physical Component Summary at 180 days post- randomization. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability
Time Frame	at 180 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	40	34
Mean (Standard Deviation) [scores on a scale]	35.51 (11.38)	38.17 (10.96)

44. Secondary Outcome

Title	SF-36 Functional Assessment Mental Component
Description	Mental Component Summary at 180 days post-randomization. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability
Time Frame	at 180 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	40	34
Mean (Standard Deviation) [scores on a scale]	45.55 (11.52)	44.08 (12.25)

45. Secondary Outcome

Title	SF-36 Functional Assessment Mental Component on Day 1
Description	SF-36 Mental Component Summary at 1 day post-randomization. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. The higher the score the less disability
Time Frame	at 1 day post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	53	35
Mean (Standard Deviation) [scores on a scale]	43.83 (12)	42.73 (13.78)

46. Secondary Outcome

Title	Patients With Serious Adverse Events
Description	Number of patients with Serious Adverse Events by day 35
Time Frame	by 35 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Number of patients with a Serious adverse event	0 0%	0 0%
Number of patients without a Serious adverse event	84 100%	72 94.7%

47. Secondary Outcome

Title	Time to Neutropenia
Description	Time to neutropenia by 35 days post-randomization
Time Frame	by 35 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Number [days]	0	0

48. Secondary Outcome

Title	Use of Granulocyte-colony Stimulating Factor
Description	Number of participants requiring Granulocyte-colony stimulating factor
Time Frame	by 35 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Number of patients that required GCSF	0 0%	0 0%
Number of patients that did not require GCSF	84 100%	72 94.7%

49. Secondary Outcome

Title	Renal Insufficiency
Description	Number of patients experiencing a glomerular filtration rate < 60mL/min at day 35
Time Frame	by 35 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Glomerular filtration rate less than 60 mL/min	36 42.9%	41 53.9%
Glomerular filtration rate greater than 60 mL/min	48 57.1%	31 40.8%

50. Secondary Outcome

Title	Red Blood Cell Transfusions Required Per Patients
Description	Red blood cell transfusions required per patients by day 35
Time Frame	by 35 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Median (Inter-Quartile Range) [transfusions]	2	1

51. Secondary Outcome

Title	Platelet Transfusions
Description	Platelet transfusions per patient
Time Frame	by 35 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	721
Median (Inter-Quartile Range) [transfusions]	1	1

52. Secondary Outcome

Title	Clinical Outcomes
Description	Composite of survival status and >7 days ventilation status, and IL-6 levels. In the composite analysis, the endpoint is composed by death, ventilation status and change of cytokine.
Time Frame	at 14 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	84	72
Number of patients with composite endpoint	42 50%	49 64.5%
Number of patients without composite endpoint	42 50%	23 30.3%

53. Secondary Outcome

Title	Bacteremia and Fungemia Outcomes
Description	Bacteremia and fungemia outcomes among subjects who survive at least 7 days
Time Frame	at 7 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	82	64
number of events	15	9
number of no events	67	55

54. Secondary Outcome

Title	Bacteremia and Fungemia Outcomes in Mechanically Ventilated Subjets
Description	Bacteremia and fungemia events among subjects who are mechanically ventilated for at least 7 through 14 days after randomization
Time Frame	at 7 through 14 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	30	33
number of events	6	9
number of no events	24	24

55. Secondary Outcome

Title	Overall Mortality
Description	Overall mortality amongst subjects who survive at least 7 days after randomization
Time Frame	at 7 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	82	64
number of deaths	16	11
number of alive	66	53

56. Secondary Outcome

Title	Number of Mechanical Ventilated Days
Description	Number of mechanical ventilated days amongst subjects who survive at least 7 days after randomization
Time Frame	at 7 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	82	64
Mean (Standard Deviation) [days]	7.05 (6.19)	9.05 (7.4)

57. Secondary Outcome

Title	Number of Ventilator-free Days
Description	Number of ventilator-free days amongst subjects who survive at least 7 days after randomization
Time Frame	at 7 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	82	64
Mean (Standard Deviation) [days]	19.17 (8.7)	17.97 (8.37)

58. Secondary Outcome

Title	Number of Days in the ICU
Description	Number of days in the ICU amongst subjects who survive at least 7 days after randomization
Time Frame	at 7 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	82	64
Mean (Standard Deviation) [days]	10.20 (6.82)	11.83 (8.32)

59. Secondary Outcome

Title	Number of ICU-free Days
Description	Number of ICU-free days amongst subjects who survive at least 7 days after randomization
Time Frame	at 7 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	82	64
Mean (Standard Deviation) [days]	15.38 (27)	13.89 (25)

60. Secondary Outcome

Title	Number of Days in the Hospital
Description	Number of days in the hospital amongst subjects who survive at least 7 days after randomization
Time Frame	at 7 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	67	57
Mean (Standard Deviation) [days]	6.21 (4.85)	5.53 (4.9)

61. Secondary Outcome

Title	Number of Hospital-free Days
Description	Number of hospital-free days amongst subjects who survive at least 7 days after randomization
Time Frame	at 7 days post-randomization

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	76	61
Mean (Standard Deviation) [days]	10.22 (8.47)	9.87 (8.09)

62. Secondary Outcome

Title	Mortality Among Subjects Mechanically Ventilated From Day 7 to 14
Description	Mortality among subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	30	33
number of events	9	6
number of no events	21	27

63. Secondary Outcome

Title	Number of Mechanically Ventilated Days Among Subjects by Day 28
Description	Number of mechanically ventilated days among subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	30	33
Mean (Standard Deviation) [days]	13.4 (6.12)	14.42 (6.64)

64. Secondary Outcome

Title	Number of Ventilator-free Days Among Subjects by Day 28
Description	Number of ventilator-free days among subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	30	33
Mean (Standard Deviation) [days]	11.4 (8.29)	12.45 (7.26)

65. Secondary Outcome

Title	Number of Days in ICU Amongst Subjects by Day 28
Description	Number of days in ICU amongst subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	30	33
Mean (Standard Deviation) [days]	16.73 (5.75)	17.79 (7.41)

66. Secondary Outcome

Title	Number of ICU-free Days Amongst Subjects by Day 28
Description	Number of ICU-free days amongst subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	30	33
Mean (Standard Deviation) [days]	7.73 (18)	8.15 (18)

67. Secondary Outcome

Title	Number of Hospital-free Days Among Subjects by Day 28
Description	Number of hospital-free days among subjects by day 28 who are mechanically ventilated for at least 7 through 14 days after randomization
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	IV Ganciclovir	Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.	normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
Measure Participants	28	32
Mean (Standard Deviation) [days]	3.54 (5.15)	4.59 (5.55)

Adverse Events

Time Frame	Clinical adverse events were collected from day 1(start of study drug) through day 35 (7 days after the stop of study drug).
Arm/Group Title	IV Ganciclovir		Placebo
Arm/Group Description	5mg/kg IV twice daily for 5 days, then followed by either IV ganciclovir or oral valganciclovir once daily until hospital discharge IV Ganciclovir: For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.		normal saline IV twice daily for 5 days, then followed by either IV normal saline or oral placebo once daily until hospital discharge Placebo: For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose. The placebo is an IV solution that does not contain any active medications.
All Cause Mortality
	IV Ganciclovir		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/84 (11.9%)		11/72 (15.3%)
Serious Adverse Events
	IV Ganciclovir		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/84 (0%)		0/72 (0%)
Other (Not Including Serious) Adverse Events
	IV Ganciclovir		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/84 (0%)		0/72 (0%)

Limitations/Caveats

Inclusion of too few trauma patients to assess treatment effects, a long enrollment window length, discontinuation of BAL sampling due to feasibility and changes in oral drug availability (later part of the study)

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.