The Safety and Effectiveness of Adefovir Dipivoxil in the Treatment of HIV-Infected Patients
A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Adefovir Dipivoxil (Bis-POM PMEA) in Prolonging Survival of HIV-Infected Individuals With a CD4+ Cell Count of <= 100/mm3 or With a CD4+ Cell Count Both > 100 and <= 200/mm3 and a Nadir CD4+ Cell Count of <= 50/mm3
2 other identifiers
interventional
505
1 country
15
Brief Summary
To evaluate the safety and efficacy of adefovir dipivoxil in prolonging survival of patients with advanced HIV disease. In CMV prophylaxis substudy: To evaluate the efficacy of adefovir dipivoxil in preventing the development of CMV end-organ disease in patients with advanced HIV coinfected with CMV. The optimal treatment for HIV infection and the prevention of CMV disease has not been identified. Currently available antiretroviral therapies are hampered by both significant toxicities and the development of resistance. In addition, agents for preventing CMV disease, such as oral ganciclovir, are complicated by poor bioavailability and decreased compliance secondary to toxicities. Moreover, discordant results have been reported regarding the effectiveness of oral ganciclovir for preventing CMV disease. There is a need for newer agents with anti-HIV and anti-herpesvirus activity that have good pharmacokinetic and safety profiles and that will be well tolerated by patients. Adefovir dipivoxil is an oral pro-drug of PMEA, a nucleoside analog with activity against a broad spectrum of retroviruses and herpesviruses, including important human pathogens, such as HIV-1, HIV-2 and CMV. Due to its anti-HIV and anti-herpesvirus activity, adefovir dipivoxil may be able to decrease the incidence of opportunistic herpesvirus infections and prolong survival in patients with advanced HIV infection.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Dec 1996
Typical duration for phase_3
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 1996
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 1999
CompletedStudy Completion
Last participant's last visit for all outcomes
August 1, 1999
CompletedFirst Submitted
Initial submission to the registry
November 2, 1999
CompletedFirst Posted
Study publicly available on registry
August 31, 2001
CompletedOctober 1, 2013
September 1, 2013
2.1 years
November 2, 1999
September 28, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Morbidity
Throughout study
Study Arms (2)
1
EXPERIMENTALParticipants will receive adefovir dipivoxil and L-carnitine
2
EXPERIMENTALParticipants will receive adefovir dipivoxil placebo and L-carnitine.
Interventions
Eligibility Criteria
You may qualify if:
- Concurrent Medication:
- Allowed:
- Chronically administered concomitant therapies for HIV and opportunistic diseases, including chemotherapy for cutaneous Kaposi's sarcoma, must be on these therapies for at least 30 days prior to study entry.
- Short courses of oral antibiotics or other therapies given for a limited period of 3 weeks.
- Episodic use of IV acyclovir or oral acyclovir \> 1g/day for treatment of acute illness is permitted at the clinician's discretion.
- Patients must have:
- A working diagnosis of HIV infection based on the patient's medical history, behavioral history, clinical signs and symptoms, or results of other laboratory tests.
- CD4+ cell count \<= 100 cells/mm3 within 60 days prior to randomization (OR, AS PER AMENDMENT 8/7/97, a CD4+ cell count that is both \> 100 and \<= 200 cells/mm3 within 60 days prior to randomization and a documented nadir CD4+ cell count \<= 50 cells/ mm3 at any time prior to randomization).
- Reasonably good health.
- Life expectancy of at least 6 months.
- Access to a refrigerator for the storage of adefovir dipivoxil.
- Signed informed consent from parent or legal guardian for patients less than 18 years of age.
- AS PER AMENDMENT 8/7/97:
- CMV serology (IgG) positive (CMV bDNA cohort and CMV-virology cohort).
You may not qualify if:
- Co-existing Condition:
- Patients with the following symptoms and conditions are excluded:
- Evidence of active CMV disease at screening.
- Concurrent Medication:
- Excluded:
- Any investigational anti-CMV agent.
- Adenine arabinoside (vidarabine).
- Amantadine hydrochloride (Symmetrel).
- Cidofovir (Vistide).
- CMV hyperimmune globulin.
- Cytosine arabinoside (cytarabine).
- Famciclovir.
- Foscarnet (phosphonoformic acid).
- Ganciclovir (Cytovene).
- GW 1263W94 (Benzamidazole).
- +29 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (15)
Community Consortium / UCSF
San Francisco, California, 94110, United States
Denver CPCRA / Denver Public Hlth
Denver, Colorado, 80204, United States
Washington Reg AIDS Prog / Dept of Infect Dis
Washington D.C., District of Columbia, 20422, United States
AIDS Research Consortium of Atlanta
Atlanta, Georgia, 30308, United States
AIDS Research Alliance - Chicago
Chicago, Illinois, 60657, United States
Louisiana Comm AIDS Rsch Prog / Tulane Univ Med
New Orleans, Louisiana, 70112, United States
Wayne State Univ - WSU/DMC / Univ Hlth Ctr
Detroit, Michigan, 48201, United States
Henry Ford Hosp
Detroit, Michigan, 48202, United States
Southern New Jersey AIDS Cln Trials / Dept of Med
Camden, New Jersey, 08103, United States
North Jersey Community Research Initiative
Newark, New Jersey, 07103, United States
Partners in Research / New Mexico
Albuquerque, New Mexico, 87131, United States
Harlem AIDS Treatment Grp / Harlem Hosp Ctr
New York, New York, 10037, United States
The Research and Education Group
Portland, Oregon, 97210, United States
Philadelphia FIGHT
Philadelphia, Pennsylvania, 19107, United States
Richmond AIDS Consortium / Div of Infect Diseases
Richmond, Virginia, 23298, United States
Related Publications (4)
Fisher E, Brosgart C, Cohn D, Chaloner K, Pulling C, Alston B, Schmetter B, El-Sadr W. Placebo (PLC)-controlled, multicenter trial of adefovir dipivoxil (ADV) in patients (pt) with HIV disease. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:160 (abstract no 491)
BACKGROUNDBrosgart C, Fisher E, Pulling C, Chaloner K, Cohn D, Elsadr W, Verheggen R, Schmetter B, Alston B. Prevalence of asymptomatic CMV retinitis (CMVR) in AIDS patients. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:152 (abstract no 453)
BACKGROUNDFisher E, Brosgart C, Cohn D, Chaloner K, Pulling C, Schmetter B, Alston B, El-Sadr W. Safety of adefovir dipivoxil (ADV) and incidence of proximal renal tubular disorder (PRTD) in a placebo (PLC)-controlled trial in patients (pt) with advanced HIV disease. Conf Retroviruses Opportunistic Infect. 1999 Jan 31-Feb 4;6th:195 (abstract no 678)
BACKGROUNDBrosgart C, Pulling C, Chaloner K, Fisher E, Coakley D, Diggins M, Ivannidis J. Serum carnitine levels in AIDS patients with advanced HIV disease from the CPCRA 039 trial. Int Conf AIDS. 1998;12:1094 (abstract no 60508)
BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
Brosgart C
- STUDY CHAIR
Fisher E
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, CARE PROVIDER
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 2, 1999
First Posted
August 31, 2001
Study Start
December 1, 1996
Primary Completion
January 1, 1999
Study Completion
August 1, 1999
Last Updated
October 1, 2013
Record last verified: 2013-09