Clinical trial NCT00006145: Preventing Cytomegalovirus (CMV) Organ Damage With Valganciclovir in People With HIV
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cytomegalovirus Infections
HIV Infections
Keywords: Ganciclovir
Cytomegalovirus
Cytomegalovirus Infections
Administration, Oral
Antiviral Agents
Polymerase Chain Reaction
Viremia
DNA, Viral
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2001-08-31
Enrollment: 350
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Alabama Therapeutics CRS
state: Alabama
city: Los Angeles
country: United States
facility: USC CRS
state: California
city: Los Angeles
country: United States
facility: UCLA CARE Center CRS
state: California
city: Palo Alto
country: United States
facility: Stanford CRS
state: California
city: San Diego
country: United States
facility: Ucsd, Avrc Crs
state: California
city: San Francisco
country: United States
facility: Ucsf Aids Crs
state: California
city: San Jose
country: United States
facility: Santa Clara Valley Med. Ctr.
state: California
city: San Mateo
country: United States
facility: San Mateo County AIDS Program
state: California
city: San Rafael
country: United States
facility: Marin County Dept. of Health & Human Services, HIV/AIDS Program & Specialty Clinic
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Washington
country: United States
facility: Georgetown University CRS (GU CRS)
state: District of Columbia
city: Miami
country: United States
facility: Univ. of Miami AIDS CRS
state: Florida
city: Atlanta
country: United States
facility: The Ponce de Leon Ctr. CRS
state: Georgia
city: Honolulu
country: United States
facility: Univ. of Hawaii at Manoa, Leahi Hosp.
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University CRS
state: Illinois
city: Chicago
country: United States
facility: Cook County Hosp. CORE Ctr.
state: Illinois
city: Chicago
country: United States
facility: Rush Univ. Med. Ctr. ACTG CRS
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ. School of Medicine, Infectious Disease Research Clinic
state: Indiana
city: Indianapolis
country: United States
facility: Indiana Univ. School of Medicine, Wishard Memorial
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Hosp. of Indiana
state: Indiana
city: Iowa City
country: United States
facility: Univ. of Iowa Healthcare, Div. of Infectious Diseases
state: Iowa
city: Baltimore
country: United States
facility: IHV Baltimore Treatment CRS
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Adult AIDS CRS
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital ACTG CRS
state: Massachusetts
city: Boston
country: United States
facility: Bmc Actg Crs
state: Massachusetts
city: Boston
country: United States
facility: BMC, Div. of Ped Infectious Diseases
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Med. Ctr., ACTG CRS
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hosp. ACTG CRS
state: Massachusetts
city: Fall River
country: United States
facility: SSTAR, Family Healthcare Ctr.
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota, ACTU
state: Minnesota
city: Saint Louis
country: United States
facility: Washington U CRS
state: Missouri
city: Omaha
country: United States
facility: Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
state: Nebraska
city: Buffalo
country: United States
facility: SUNY - Buffalo, Erie County Medical Ctr.
state: New York
city: New York
country: United States
facility: Beth Israel Med. Ctr., ACTU
state: New York
city: New York
country: United States
facility: Cornell CRS
state: New York
city: New York
country: United States
facility: NY Univ. HIV/AIDS CRS
state: New York
city: New York
country: United States
facility: Weill Med. College of Cornell Univ., The Cornell CTU
state: New York
city: New York
country: United States
facility: Columbia Univ., HIV Prevention and Treatment Medical Ctr.
state: New York
city: Rochester
country: United States
facility: AIDS Care CRS
state: New York
city: Rochester
country: United States
facility: McCree McCuller Wellness Ctr. at the Connection, Infectious Disease Unit
state: New York
city: Rochester
country: United States
facility: Univ. of Rochester ACTG CRS
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs
state: North Carolina
city: Cincinnati
country: United States
facility: Univ. of Cincinnati CRS
state: Ohio
city: Cleveland
country: United States
facility: Case CRS
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth CRS
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation, Div. of Medicine, Infectious Diseases
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Hosp. of the Univ. of Pennsylvania CRS
state: Pennsylvania
city: Philadelphia
country: United States
facility: Univ. of Pennsylvania Health System, Presbyterian Med. Ctr.
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Pitt CRS
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hosp.
state: Rhode Island
city: Providence
country: United States
facility: The Miriam Hosp. ACTG CRS
state: Rhode Island
city: Nashville
country: United States
facility: Vanderbilt Therapeutics CRS
state: Tennessee
city: Dallas
country: United States
facility: Univ. of Texas Southwestern Med. Ctr., Amelia Court Continuity Clinic
state: Texas
city: Galveston
country: United States
facility: Univ. of Texas Medical Branch, ACTU
state: Texas
city: Seattle
country: United States
facility: University of Washington AIDS CRS
state: Washington
city: San Juan
country: Puerto Rico
facility: Puerto Rico-AIDS CRS
Study officials:
affiliation: University of California, San Francisco and San Francisco General Hospital
name: Mark Jacobson, MD
role: STUDY_CHAIR
affiliation: University of North Carolina, Chapel Hill
name: David A. Wohl, MD
role: STUDY_CHAIR
References:
citation: Cocohoba JM, McNicholl IR. Valganciclovir: an advance in cytomegalovirus therapeutics. Ann Pharmacother. 2002 Jun;36(6):1075-9. doi: 10.1345/aph.1A393.
citation: De Clercq E. Antiviral drugs in current clinical use. J Clin Virol. 2004 Jun;30(2):115-33. doi: 10.1016/j.jcv.2004.02.009.
citation: 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. doi: 10.1086/375843. Epub 2003 Jul 29.
citation: 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. doi: 10.1517/13543784.10.9.1745.
citation: Wohl DA, Kendall MA, Andersen J, Crumpacker C, Spector SA, Feinberg J, Alston-Smith B, Owens S, Chafey S, Marco M, Maxwell S, Lurain N, Jabs D, Benson C, Keiser P, Jacobson MA; A5030 Study Team. Low rate of CMV end-organ disease in HIV-infected patients despite low CD4+ cell counts and CMV viremia: results of ACTG protocol A5030. HIV Clin Trials. 2009 May-Jun;10(3):143-52. doi: 10.1310/hct1003-143.