Preventing Cytomegalovirus (CMV) Organ Damage With Valganciclovir in People With HIV

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00006145
• Collaborator: (none)
• Enrollment: 350
• Locations: 57
• Duration (Months): 66
• Patients Per Site: 6.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Cytomegalovirus (CMV) infection is a common opportunistic infection (OI) in HIV patients. The purpose of this study is to find out whether valganciclovir, an antiviral approved by the FDA for the treatment of CMV in the eye, is safe and effective in preventing CMV organ damage in people with HIV.

Condition or Disease	Intervention/Treatment	Phase
Cytomegalovirus Infections; HIV Infections	Drug: Valganciclovir	Phase 3

Detailed Description

CMV infection, most commonly of the retina (also known as CMV retinitis), is a common OI observed in HIV patients. Despite treatment, CMV retinitis can result in severe visual impairment and CMV disease is associated with reduced survival time. HIV patients receiving highly active antiretroviral therapy (HAART) for HIV infection who have CD4 counts less than 100 cells/mm3 may be at increased risk of CMV infection and its complications. Valganciclovir was approved by the FDA on March 29, 2001 for treatment of the symptoms of CMV retinitis in patients with weakened immune systems, including people with HIV and AIDS. This study will evaluate the safety and efficacy of valganciclovir in preventing CMV organ damage in HIV patients.

This study will last approximately 6 years. Step 1 is the longitudinal screening phase of the study. Patients at high risk for CMV disease who are enrolled in the study will be screened every 8 weeks for CMV in the blood; medical history assessment, physical examination, and blood work will occur at each visit. Additional blood collection to monitor HIV infection will occur every 16 weeks. Patients will undergo opthalmologic examination every 24 weeks. Patients who develop detectable CMV in their blood during Step 1 then enter Step 2 of the study.

In version 3.0 of this study, participants who test positive for CMV viremia or who are currently in Step 2 will be automatically enrolled into Step 4 and will be randomly assigned to one of two groups: 1) 900 mg valganciclovir twice daily for 3 weeks, followed by 900 mg valganciclovir daily, or 2) placebo. Participants will enter Step 3 if and when they develop CMV end-organ disease, at which point all participants will be offered 900 mg valganciclovir twice daily for 3 weeks, then 900 valganciclovir daily thereafter.

Study Design

• Study Type: Interventional
• Masking: Double
• Primary Purpose: Prevention
• Official Title: A Phase III, Prospective, Randomized, Double-Blind Trial of Valganciclovir Pre-Emptive Therapy for Cytomegalovirus (CMV) Viremia as Detected by Plasma CMV DNA PCR Assay
• Study Start Date: Aug 1, 2000
• Actual Study Completion Date: Feb 1, 2006

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

• Ages Eligible for Study: 13 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Note: Per a recommendation from NIAID Therapeutic Trials Data Safety Monitoring Board (DSMB), this trial will close on 10/03/05. The DSMB has determined that the study will reach the primary objective. All participants not on valganciclovir must complete all study evaluations by 08/31/05; all participants taking valganciclovir must complete study evaluations by 10/03/05.

Inclusion Criteria for Step 1:

• HIV infected

• Viral load greater than 400 copies/ml

• CD4 count less than 100 cells/mm3

• Have taken HAART for 3 months or longer OR are not taking HAART and do not plan to start HAART for at least 3 months after study entry

• Have serum CMV IgG antibodies

• Have consent of parent or guardian if under 18 years of age

• Willing to use acceptable forms of contraception

Exclusion Criteria for Step 1:

• History of CMV end-organ disease

• Certain antiviral drugs for CMV prophylaxis within 8 weeks of study entry

• Pregnant or breastfeeding

• Currently require ongoing foscarnet or cidofovir. Limited courses of foscarnet or cidofovir for the treatment of diseases other than CMV are permitted if approved by the protocol chairs.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Alabama Therapeutics CRS	Birmingham	Alabama	United States	35294
2	USC CRS	Los Angeles	California	United States	90033
3	UCLA CARE Center CRS	Los Angeles	California	United States	90095
4	Stanford CRS	Palo Alto	California	United States	94305
5	Ucsd, Avrc Crs	San Diego	California	United States	92103
6	Ucsf Aids Crs	San Francisco	California	United States	94110
7	Santa Clara Valley Med. Ctr.	San Jose	California	United States	95128
8	San Mateo County AIDS Program	San Mateo	California	United States	94305
9	Marin County Dept. of Health & Human Services, HIV/AIDS Program & Specialty Clinic	San Rafael	California	United States	94903
10	University of Colorado Hospital CRS	Aurora	Colorado	United States	80262
11	Georgetown University CRS (GU CRS)	Washington	District of Columbia	United States	20007
12	Univ. of Miami AIDS CRS	Miami	Florida	United States	33136
13	The Ponce de Leon Ctr. CRS	Atlanta	Georgia	United States	30308
14	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii	United States	96816
15	Northwestern University CRS	Chicago	Illinois	United States	60611
16	Cook County Hosp. CORE Ctr.	Chicago	Illinois	United States	60612
17	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois	United States	60612
18	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana	United States	46202
19	Indiana Univ. School of Medicine, Wishard Memorial	Indianapolis	Indiana	United States	46202
20	Methodist Hosp. of Indiana	Indianapolis	Indiana	United States	46202
21	Univ. of Iowa Healthcare, Div. of Infectious Diseases	Iowa City	Iowa	United States	52242
22	IHV Baltimore Treatment CRS	Baltimore	Maryland	United States	21201
23	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland	United States	21287
24	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts	United States	02114
25	Bmc Actg Crs	Boston	Massachusetts	United States	02118
26	BMC, Div. of Ped Infectious Diseases	Boston	Massachusetts	United States	02118
27	Beth Israel Deaconess Med. Ctr., ACTG CRS	Boston	Massachusetts	United States	02215
28	Brigham and Women's Hosp. ACTG CRS	Boston	Massachusetts	United States	02215
29	SSTAR, Family Healthcare Ctr.	Fall River	Massachusetts	United States	02720
30	University of Minnesota, ACTU	Minneapolis	Minnesota	United States	55455
31	Washington U CRS	Saint Louis	Missouri	United States	63110
32	Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.	Omaha	Nebraska	United States	68198
33	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York	United States	14215
34	Beth Israel Med. Ctr., ACTU	New York	New York	United States	10003
35	Cornell CRS	New York	New York	United States	10011
36	NY Univ. HIV/AIDS CRS	New York	New York	United States	10016
37	Weill Med. College of Cornell Univ., The Cornell CTU	New York	New York	United States	10021
38	Columbia Univ., HIV Prevention and Treatment Medical Ctr.	New York	New York	United States	10032
39	AIDS Care CRS	Rochester	New York	United States	14607
40	McCree McCuller Wellness Ctr. at the Connection, Infectious Disease Unit	Rochester	New York	United States	14642
41	Univ. of Rochester ACTG CRS	Rochester	New York	United States	14642
42	Unc Aids Crs	Chapel Hill	North Carolina	United States	27599
43	Univ. of Cincinnati CRS	Cincinnati	Ohio	United States	45267
44	Case CRS	Cleveland	Ohio	United States	44106
45	MetroHealth CRS	Cleveland	Ohio	United States	44109
46	Cleveland Clinic Foundation, Div. of Medicine, Infectious Diseases	Cleveland	Ohio	United States	44195
47	The Ohio State University Medical Center	Columbus	Ohio	United States	43210
48	Hosp. of the Univ. of Pennsylvania CRS	Philadelphia	Pennsylvania	United States	19104
49	Univ. of Pennsylvania Health System, Presbyterian Med. Ctr.	Philadelphia	Pennsylvania	United States	19104
50	Pitt CRS	Pittsburgh	Pennsylvania	United States	15213
51	Rhode Island Hosp.	Providence	Rhode Island	United States	02906
52	The Miriam Hosp. ACTG CRS	Providence	Rhode Island	United States	02906
53	Vanderbilt Therapeutics CRS	Nashville	Tennessee	United States	37203
54	Univ. of Texas Southwestern Med. Ctr., Amelia Court Continuity Clinic	Dallas	Texas	United States	75235
55	Univ. of Texas Medical Branch, ACTU	Galveston	Texas	United States	77555
56	University of Washington AIDS CRS	Seattle	Washington	United States	98104
57	Puerto Rico-AIDS CRS	San Juan		Puerto Rico	00935

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Study Chair: Mark Jacobson, MD, University of California, San Francisco and San Francisco General Hospital
• Study Chair: David A. Wohl, MD, University of North Carolina, Chapel Hill

Study Documents (Full-Text)

None provided.

More Information

Publications

• Cocohoba JM, McNicholl IR. Valganciclovir: an advance in cytomegalovirus therapeutics. Ann Pharmacother. 2002 Jun;36(6):1075-9. Review.
• De Clercq E. Antiviral drugs in current clinical use. J Clin Virol. 2004 Jun;30(2):115-33. Review.
• Erice A, Tierney C, Hirsch M, Caliendo AM, Weinberg A, Kendall MA, Polsky B; AIDS Clinical Trials Group Protocol 360 Study Team. Cytomegalovirus (CMV) and human immunodeficiency virus (HIV) burden, CMV end-organ disease, and survival in subjects with advanced HIV infection (AIDS Clinical Trials Group Protocol 360). Clin Infect Dis. 2003 Aug 15;37(4):567-78. Epub 2003 Jul 29.
• Reusser P. Oral valganciclovir: a new option for treatment of cytomegalovirus infection and disease in immunocompromised hosts. Expert Opin Investig Drugs. 2001 Sep;10(9):1745-53. Review.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00006145
• Other Study ID Numbers: A5030; 10170; ACTG A5030; AACTG A5030
• First Posted: Aug 31, 2001
• Last Update Posted: Nov 1, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): Ganciclovir; Cytomegalovirus; Cytomegalovirus Infections; Administration, Oral; Antiviral Agents; Polymerase Chain Reaction; Viremia; DNA, Viral
• Additional relevant MeSH terms: Infections; Communicable Diseases; Cytomegalovirus Infections; Valganciclovir

Study Results

No Results Posted as of Nov 1, 2021