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
Levocarnitine
+ Adefovir dipivoxil
+ Levocarnitine
Blood-Borne Infections+14
+ Urogenital Diseases
+ Genital Diseases
Treatment Study
Summary
Study start date: December 1, 1996
Actual date on which the first participant was enrolled.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: Safety-HIV virology cohort (at least the first 400 patients enrolled in the study regardless of CMV status). CMV bDNA cohort (those patients in the safety-HIV virology cohort who are CMV-positive). CMV-virology cohort (the first 400 patients in the CMV bDNA cohort enrolled at sites able to obtain CMV urine cultures). All patients who are CMV-positive are enrolled in the CMV prophylaxis substudy.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.505 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.Over 13 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
Inclusion Criteria 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). Exclusion Criteria Co-existing Condition: Patients with the following symptoms and conditions are excluded: Evidence of active CMV disease at screening. Conditions that would require use of medications listed in Exclusion Concurrent Medications. 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). Idoxuridine. Intravenous acyclovir. ISIS 2922 (Anti-sense). Lobucavir. MSL109. Oral acyclovir > 1 g/day. Valacyclovir. Patients with the following prior conditions are excluded: History of CMV end-organ disease. Prior Medication: Excluded within 2 weeks of randomization: Any investigational anti-CMV agent. Adenine arabinoside (vidarabine). Amantadine hydrochloride (Symmetrel). Cidofovir (Vistide). CMV hyperimmune globulin. Cytosine arabinoside (cytarabine). Famciclovir. Ganciclovir (Cytovene). GW 1263W94 (Benzamidazole). Idoxuridine. Intravenous acyclovir. ISIS 2922 (Anti-sense). Lobucavir. MSL109. Oral acyclovir > 1 g/day. Valacyclovir. Excluded within 60 days prior to study entry: Foscarnet.
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.2 intervention groups are designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalGroup II
ExperimentalStudy Objectives
Primary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 15 locations
Community Consortium / UCSF
San Francisco, United StatesOpen Community Consortium / UCSF in Google MapsDenver CPCRA / Denver Public Hlth
Denver, United StatesWashington Reg AIDS Prog / Dept of Infect Dis
Washington D.C., United StatesAIDS Research Consortium of Atlanta
Atlanta, United States