|
|
|
|
|
|
Sponsored by: |
National Institute of Allergy and Infectious Diseases (NIAID) |
Information provided by: | National Institute of Allergy and Infectious Diseases (NIAID) |
ClinicalTrials.gov Identifier: | NCT00001082 |
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.
Condition | Intervention | Phase |
Cytomegalovirus Infections HIV Infections |
Drug: Levocarnitine Drug: Adefovir dipivoxil Drug: Adefovir dipivoxil placebo |
Phase III |
MedlinePlus related topics: | AIDS Cytomegalovirus Infections |
Drug Information available for: | Adefovir dipivoxil Adefovir Carnitine Adenine |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double Blind (Subject, Caregiver), Parallel Assignment, Safety Study |
Official Title: | 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 |
Enrollment: | 505 |
Study Start Date: | December 1996 |
Primary Completion Date: | January 1999 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
1: Experimental
Participants will receive adefovir dipivoxil and L-carnitine
|
Drug: Levocarnitine
500 mg tablet taken orally daily
Drug: Adefovir dipivoxil
120 mg tablet taken orally daily
|
2: Experimental
Participants will receive adefovir dipivoxil placebo and L-carnitine.
|
Drug: Levocarnitine
500 mg tablet taken orally daily
Drug: Adefovir dipivoxil placebo
Oral placebo tablet taken daily
|
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.
All patients will be enrolled within the first 18 months of the study. They will be randomized to 1 of 2 groups. Group 1 will be comprised of 1080 patients and will receive adefovir dipivoxil plus L-carnitine and group 2 will be comprised of 1080 patients and will receive a placebo plus L-carnitine. At least the first 400 patients enrolled (200 in each group) will comprise the safety-HIV virology cohort. These patients will have more frequent follow up visits, additional laboratory evaluations, and more intensive safety data information during the first 6 months. NOTE: At least 850 patients who are infected with CMV are followed for the development of CMV end-organ disease in a CMV prophylaxis substudy.
AS PER AMENDMENT 8/7/97: All patients are enrolled in the primary study and randomized to the treatment or placebo regimen. Within the primary study, patients meeting specified criteria may be enrolled in one or more of the following cohorts:
All patients who are CMV-positive are enrolled in the CMV prophylaxis substudy.
Ages Eligible for Study: | 13 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria
Concurrent Medication:
Allowed:
Patients must have:
AS PER AMENDMENT 8/7/97:
Exclusion Criteria
Co-existing Condition:
Patients with the following symptoms and conditions are excluded:
Concurrent Medication:
Excluded:
Patients with the following prior conditions are excluded:
Prior Medication:
Excluded within 2 weeks of randomization:
Excluded within 60 days prior to study entry:
United States, California | |||||
Community Consortium / UCSF | |||||
San Francisco, California, United States, 94110 | |||||
United States, Colorado | |||||
Denver CPCRA / Denver Public Hlth | |||||
Denver, Colorado, United States, 802044507 | |||||
United States, District of Columbia | |||||
Washington Reg AIDS Prog / Dept of Infect Dis | |||||
Washington, District of Columbia, United States, 20422 | |||||
United States, Georgia | |||||
AIDS Research Consortium of Atlanta | |||||
Atlanta, Georgia, United States, 303081962 | |||||
United States, Illinois | |||||
AIDS Research Alliance - Chicago | |||||
Chicago, Illinois, United States, 60657 | |||||
United States, Louisiana | |||||
Louisiana Comm AIDS Rsch Prog / Tulane Univ Med | |||||
New Orleans, Louisiana, United States, 70112 | |||||
United States, Michigan | |||||
Henry Ford Hosp | |||||
Detroit, Michigan, United States, 48202 | |||||
Wayne State Univ - WSU/DMC / Univ Hlth Ctr | |||||
Detroit, Michigan, United States, 48201 | |||||
United States, New Jersey | |||||
North Jersey Community Research Initiative | |||||
Newark, New Jersey, United States, 071032842 | |||||
Southern New Jersey AIDS Cln Trials / Dept of Med | |||||
Camden, New Jersey, United States, 08103 | |||||
United States, New Mexico | |||||
Partners in Research / New Mexico | |||||
Albuquerque, New Mexico, United States, 87131 | |||||
United States, New York | |||||
Harlem AIDS Treatment Grp / Harlem Hosp Ctr | |||||
New York, New York, United States, 10037 | |||||
United States, Oregon | |||||
The Research and Education Group | |||||
Portland, Oregon, United States, 97210 | |||||
United States, Pennsylvania | |||||
Philadelphia FIGHT | |||||
Philadelphia, Pennsylvania, United States, 19107 | |||||
United States, Virginia | |||||
Richmond AIDS Consortium / Div of Infect Diseases | |||||
Richmond, Virginia, United States, 232980049 |
Study Chair: | Brosgart C | |
Study Chair: | Fisher E |
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)
  |
Brosgart 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)
  |
Fisher 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)
  |
Brosgart 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)
  |
Responsible Party: | DAIDS ( Rona Siskind ) |
Study ID Numbers: | CPCRA 039 |
First Received: | November 2, 1999 |
Last Updated: | September 25, 2008 |
ClinicalTrials.gov Identifier: | NCT00001082 |
Health Authority: | United States: Federal Government |
|
|
|
|
|
|