Rapid Empiric Treatment With Oseltamivir Study (RETOS)

• Sponsor: University of Louisville (Other)
• Overall Status: Completed
• CT.gov ID: NCT01248715
• Collaborator: Centers for Disease Control and Prevention (U.S. Fed)
• Enrollment: 1,107
• Locations: 5
• Arms: 2
• Duration (Months): 66
• Patients Per Site: 221.4
• Patients Per Site Per Month: 3.4

Study Details

Study Description

Brief Summary

Current guidelines recommend early initiation of empiric antibiotic therapy to cover typical and atypical bacteria that may cause community-acquired pneumonia (CAP). Influenza antiviral therapy in patients with suspected or confirmed influenza. However, many clinicians do not suspect influenza among patients with CAP or other acute lower respiratory tract illness (LRTI) and often do not test for influenza. Additionally, results from currently available diagnostic tests for influenza may be delayed and several tests have low sensitivity and will give false negative results. Thus, anti-influenza treatment for patients with hospitalized influenza CAP and LRTI is frequently initiated late if at all. There is an association between delayed time to administration of empiric antibiotic therapy with increased clinical failure and mortality. As a result, empiric antibiotic therapy for patients with suspect CAP is begun within 4 - 6 hours of hospitalization. This has recently been demonstrated for delayed antiviral treatment as well. We hypothesize that, as happens with early empiric antibiotics for bacterial CAP, a standardized approach of adding early empiric anti-influenza therapy during the influenza season to hospitalized patients with suspect CAP and LRTI will improve clinical outcomes of patients with influenza associated CAP and LRTI.

To test our hypothesis we plan a prospective, randomized, multicenter clinical trial of hospitalized patients with acute LRTI, including suspect CAP, during . If early anti-influenza medications were not included on the patients admission orders, patients will be randomized to standard care, including empiric antibacterial therapy as recommended by ATS/IDSA guidelines plus standard influenza diagnostics and treatment (Standard of care) versus early initiation of empiric antiinfluenza therapy plus standard care, e.g. empiric antibacterial (oseltamivir group). The primary study outcome will be development of clinical failure and selected clinical outcomes during the 30 days after enrollment. Other clinical outcomes that will be compared between study groups include time to clinical stability, duration of hospitalization, development of cardiovascular events, re-hospitalization, short-term mortality (30 days), and long-term mortality (1 year). The secondary study outcome will be the cost-effectiveness of the intervention.

Condition or Disease	Intervention/Treatment	Phase
Influenza; Pneumonia	Drug: oseltamivir	Phase 4

Detailed Description

This will be both a prospective, randomized, unblinded clinical study of hospitalized patients with acute LRTI admitted in one of four institutions in Louisville, KY (rapid empiric treatment with oseltamivir study[RETOS]) and a prospective observation study to describe influenza LRTI (Flu LRTI study). All hospitalized patients with acute LRTI will be invited to participate in one of the arms of study. If the admitting clinician does not order oseltamivir or zanamivir at the time of hospital admission, the patient is eligible for randomization into Group A (standard clinical care, including empiric antibiotics and anti-influenza drugs at the clinician discretion) or Group B (oseltamivir administered to the patient within 24 hours of admission, ideally within 8-12 hours of admission, plus empiric antibiotics).

Patients will be enrolled from one of four hospitals, the University of Louisville Hospital, Veterans Affairs Medical Center of Louisville, Norton Hospital of Louisville, and Jewish Hospital of Louisville. Eligible patients will be identified primarily in the Emergency Departments of all four hospitals and evaluated for inclusion/exclusion criteria after hospital admission orders are written. Patients will be enrolled only during the influenza season. For this study, the influenza season is defined as December 1st until May 1st, unless surveillance data suggests that influenza viruses are circulating earlier or have stopped circulating.

For all three study groups, diagnosis of influenza will be based on nucleic acid amplification through polymerase chain reaction (PCR). At the time of enrollment into the study, a nasopharyngeal swab will be obtained for PCR. The University of Louisville Infectious Diseases Reference Laboratory has extensive experience using molecular techniques for the diagnosis of respiratory pathogens and will test batched specimens at monthly intervals. In addition, we will collect the results from tests done for routine care and bacterial or virus isolates identified during routine care for further characterization.

The management of patients in Group A and Group B will be different only in regard to early empiric anti-influenza therapy. All other aspects of the management of these patients will be in compliance with national guideline recommendations from IDSA/ATS (2). Patients in Group A may have antiviral therapy started later in hospitalization or not treated at all. The study will not interfere with Group A patient care.

A 1:1 randomization ratio within the two study arms is planned for EOS. A pre-defined randomization chart will be designed in order to have the randomization process Internet-based. The randomization table will be accessible by the project manager as a back up in the event that any problem occurs with the Internet or the computerized system.

We will attempt to begin oseltamivir within 8 - 12 hours after hospital admission, and no later than 24 hours. The study nurse will facilitate receipt of early oseltamivir treatment for the consented patient in collaboration with the hospital pharmacies. The time of oseltamivir administration will be recorded for all enrolled patients.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1107 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Title: Effectiveness of Empiric Antiviral Treatment for Hospitalized Community Acquired Pneumonia During the Influenza Season (U18)
• Study Start Date: Nov 1, 2010
• Actual Primary Completion Date: May 1, 2016
• Actual Study Completion Date: May 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oseltamirvir These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy.	Drug: oseltamivir; These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability; Other Names: Tamiflu
No Intervention: Standard of care These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Clinical Failure (Failure to Reach Clinical Stability) [7 days]

   Number of subject that showed lack of clinical improvement within 7 days. Criteria for clinical improvement include no fever; white blood cell count decreases, or increases in the case of leukopenia, to more than 10% from the prior day; the evaluation of signs and symptoms of CAP to define when the patient is subjectively better, and the patient is able to tolerate food by mouth.

2. Number of Participants to Transfer to ICU After 24 h [24 h]

   Number of subjects that were transfered to an intensive care unit (ICU) after 24 hours of hospitalization. A patient transferred to ICU within 24 hours of admission was considered as a direct admission to ICU and not meeting criteria for clinical failure.

3. Number of Participants That Required Re-hospitalization [30 days]

   Participants that were re-hospitalized within 30 days after enrollment.

4. Number of Participants That Had Short-term Mortality [30 days]

   Number of subjects who died within 30 days of enrollment

Secondary Outcome Measures

1. Days to Reach Clinical Stability [30 days]

   Time to clinical improvement. The criteria for clinical improvement were followed during the first week from the day of admission and defined as follows: a) improvement of signs and symptoms of LRTI reported by patient b) afebrile for at least 8 hours, c) decrease in white blood cell count to more than 10% from the prior day, and d) able to tolerate oral feeding. A patient was considered clinically improved on the day that these four criteria were all met.

2. Length of Hospital Stay [through study completion, up to 30 days]

   Duration of hospitalization calculated as the day of discharge minus the day of admission.

3. Number of Participants With Hospital Mortality. [through study completion, up to 30 days]

   Number of subjects who died while hospitalized

Eligibility Criteria

Criteria

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

Inclusion Criteria:

For oseltamivir and standard of care groups:

• 18 years of age or older

• No oseltamivir or zanamivir ordered in hospital admission orders

• Meets criteria for acute LRTI

• Signed informed consent.

Exclusion Criteria:

For oseltamivir and standard of care groups:

• Oseltamivir or zanamivir ordered in hospital admission orders

• Patients hospitalized for the LRTI for more than 24 hours before enrollment into the trial.

• Patients with mental conditions who are unlikely to comply with the study protocol and who cannot give informed consent and have no guardian or proxy.

• Patients who have had severe allergic reactions such as anaphylaxis or serious skin reactions such as toxic epidermal necrolysis, Stevens-Johnson syndrome, or erythema multiforme to any component of oseltamivir (TAMIFLU).

• Prisoners

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jewish Hospital	Louisville	Kentucky	United States	40202
2	Norton Hospital	Louisville	Kentucky	United States	40202
3	University of Louisville Hospital	Louisville	Kentucky	United States	40202
4	Rex Robley VA Medical Center	Louisville	Kentucky	United States	40206
5	Baptist Hospital East	Louisville	Kentucky	United States	40272

Sponsors and Collaborators

• University of Louisville
• Centers for Disease Control and Prevention

Investigators

• Principal Investigator: Julio A Ramirez, MD, University of Louisville

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• National Center for Health Statistics

Publications

• Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007 Mar 1;44 Suppl 2:S27-72.

• Responsible Party: Julio Ramirez, Professor, University of Louisville
• ClinicalTrials.gov Identifier: NCT01248715
• Other Study ID Numbers: RETOS
• First Posted: Nov 25, 2010
• Last Update Posted: Nov 6, 2017
• Last Verified: Oct 1, 2017

• Keywords provided by Julio Ramirez, Professor, University of Louisville: pneumonia, bacterial; pneumonia, viral; respiratory tract infections; oseltamivir, therapeutic use
• Additional relevant MeSH terms: Influenza, Human; Pneumonia; Oseltamivir

Study Results

Participant Flow

Arm/Group Title	Oseltamirvir	Standard of Care
Arm/Group Description	These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy. oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability	These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.
Period Title: Overall Study
STARTED	556	551
COMPLETED	55	41
NOT COMPLETED	501	510

Baseline Characteristics

Arm/Group Title	Oseltamirvir	Standard of Care	Total
Arm/Group Description	These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy. oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability	These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.	Total of all reporting groups
Overall Participants	55	41	96
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	63	60	61.7
Sex: Female, Male (Count of Participants)
Female	23 41.8%	23 56.1%	46 47.9%
Male	32 58.2%	18 43.9%	50 52.1%
Region of Enrollment (Count of Participants)
United States	55 100%	41 100%	96 100%
Nursing home Resident (Count of Participants)
Count of Participants [Participants]	0 0%	2 4.9%	2 2.1%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Clinical Failure (Failure to Reach Clinical Stability)
Description	Number of subject that showed lack of clinical improvement within 7 days. Criteria for clinical improvement include no fever; white blood cell count decreases, or increases in the case of leukopenia, to more than 10% from the prior day; the evaluation of signs and symptoms of CAP to define when the patient is subjectively better, and the patient is able to tolerate food by mouth.
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oseltamirvir	Standard of Care
Arm/Group Description	These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy. oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability	These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.
Measure Participants	55	41
Count of Participants [Participants]	6 10.9%	2 4.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oseltamirvir, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.460
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

2. Primary Outcome

Title	Number of Participants to Transfer to ICU After 24 h
Description	Number of subjects that were transfered to an intensive care unit (ICU) after 24 hours of hospitalization. A patient transferred to ICU within 24 hours of admission was considered as a direct admission to ICU and not meeting criteria for clinical failure.
Time Frame	24 h

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oseltamirvir	Standard of Care
Arm/Group Description	These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy. oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability	These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.
Measure Participants	55	41
Count of Participants [Participants]	2 3.6%	2 4.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oseltamirvir, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.9999
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

3. Primary Outcome

Title	Number of Participants That Required Re-hospitalization
Description	Participants that were re-hospitalized within 30 days after enrollment.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oseltamirvir	Standard of Care
Arm/Group Description	These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy. oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability	These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.
Measure Participants	55	41
Count of Participants [Participants]	5 9.1%	5 12.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oseltamirvir, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.732
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

4. Primary Outcome

Title	Number of Participants That Had Short-term Mortality
Description	Number of subjects who died within 30 days of enrollment
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oseltamirvir	Standard of Care
Arm/Group Description	These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy. oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability	These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.
Measure Participants	55	41
Count of Participants [Participants]	2 3.6%	1 2.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oseltamirvir, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.9999
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

5. Secondary Outcome

Title	Days to Reach Clinical Stability
Description	Time to clinical improvement. The criteria for clinical improvement were followed during the first week from the day of admission and defined as follows: a) improvement of signs and symptoms of LRTI reported by patient b) afebrile for at least 8 hours, c) decrease in white blood cell count to more than 10% from the prior day, and d) able to tolerate oral feeding. A patient was considered clinically improved on the day that these four criteria were all met.
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oseltamirvir	Standard of Care
Arm/Group Description	These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy. oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability	These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.
Measure Participants	55	41
Median (Inter-Quartile Range) [days]	2	2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oseltamirvir, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.685
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

6. Secondary Outcome

Title	Length of Hospital Stay
Description	Duration of hospitalization calculated as the day of discharge minus the day of admission.
Time Frame	through study completion, up to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oseltamirvir	Standard of Care
Arm/Group Description	These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy. oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability	These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.
Measure Participants	55	41
Median (Inter-Quartile Range) [days]	4	4.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oseltamirvir, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.796
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

7. Secondary Outcome

Title	Number of Participants With Hospital Mortality.
Description	Number of subjects who died while hospitalized
Time Frame	through study completion, up to 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Oseltamirvir	Standard of Care
Arm/Group Description	These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy. oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability	These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.
Measure Participants	55	41
Count of Participants [Participants]	1 1.8%	1 2.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oseltamirvir, Standard of Care
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.9999
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Arm/Group Title	Oseltamirvir		Standard of Care
Arm/Group Description	These patients will receive early oseltamivir plus current, standard empiric antibacterial therapy. oseltamivir: These patients will receive early (within 8-12 hours of admission, no later than 24 hours after admission) oseltamivir plus current, standard empiric antibacterial therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP (2). Anti-influenza therapy will be given using oseltamivir at a dose of 75 mg twice daily. The oseltamivir dose will be adjusted in patients with renal insufficiency according to the package insert. Duration of antiviral therapy will be for a minimum of 5 days for patients with evidence of early clinical improvement and prolonged depending on clinical stability		These patients will be treated with the current, standard care, including currently recommended antibiotics or antiviral therapy based on national recommendations from the IDSA/ATS guidelines for management of hospitalized patients with CAP and ACIP antiviral use guidelines for hospitalized patients with confirmed of suspect influenza, per clinician discretion. In addition these patients with have a NP swab collected for influenza PCR testing and clinical information will be extracted from the medical record.
All Cause Mortality
	Oseltamirvir		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/55 (3.6%)		1/41 (2.4%)
Serious Adverse Events
	Oseltamirvir		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		1/41 (2.4%)
Cardiac disorders
Cardiovascular event	0/55 (0%)	0	1/41 (2.4%)	1
Other (Not Including Serious) Adverse Events
	Oseltamirvir		Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/41 (0%)

Limitations/Caveats

The primary limitation of our study that we were not able to reach the number of patients that were estimated in the sample size calculation.

More Information

Certain Agreements

All Principal Investigators ARE 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.