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Cytomegalovirus InfectionsPhase 3NCT00001082

The Safety and Effectiveness of Adefovir Dipivoxil in the Treatment of HIV-Infected Patients

A Phase 3 study testing Levocarnitine and Adefovir dipivoxil in people with Cytomegalovirus Infections and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 13 years and older
Conditions the study is for
Cytomegalovirus Infections, HIV Infections
What is being tested?
Levocarnitine and Adefovir dipivoxil
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
505 participants
Where
15 sitesUnited States
Study dates
Dec 1996to Aug 1999
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 13 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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:
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  • 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).

Who cannot join

  • 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:
Show all 45Show fewer
  • 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.

Trial locations and contacts

15 sites in 1 country.

15 sites in 1 country

United States15 sites
  • Partners in Research / New Mexico

    Albuquerque, New Mexico, 87131

  • AIDS Research Consortium of Atlanta

    Atlanta, Georgia, 30308

  • Southern New Jersey AIDS Cln Trials / Dept of Med

    Camden, New Jersey, 08103

  • AIDS Research Alliance - Chicago

    Chicago, Illinois, 60657

  • Denver CPCRA / Denver Public Hlth

    Denver, Colorado, 80204

  • Wayne State Univ - WSU/DMC / Univ Hlth Ctr

    Detroit, Michigan, 48201

  • Henry Ford Hosp

    Detroit, Michigan, 48202

  • Louisiana Comm AIDS Rsch Prog / Tulane Univ Med

    New Orleans, Louisiana, 70112

  • Harlem AIDS Treatment Grp / Harlem Hosp Ctr

    New York, New York, 10037

  • North Jersey Community Research Initiative

    Newark, New Jersey, 07103

  • Philadelphia FIGHT

    Philadelphia, Pennsylvania, 19107

  • The Research and Education Group

    Portland, Oregon, 97210

  • Richmond AIDS Consortium / Div of Infect Diseases

    Richmond, Virginia, 23298

  • Community Consortium / UCSF

    San Francisco, California, 94110

  • Washington Reg AIDS Prog / Dept of Infect Dis

    Washington D.C., District of Columbia, 20422

Other trials in United States

About this 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

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.

Read the detailed description

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:

  1. Safety-HIV virology cohort (at least the first 400 patients enrolled in the study regardless of CMV status).
  2. CMV bDNA cohort (those patients in the safety-HIV virology cohort who are CMV-positive).
  3. 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.

Being tested
Levocarnitine, Adefovir dipivoxil, Adefovir dipivoxil placebo
Keywords
Cytomegalovirus Infections, Antiviral Agents, CD4 Lymphocyte Count, Prodrugs, Survival, Adenine
Medical subject headings
Cytomegalovirus Infections, HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LevocarnitineDrug

    Also called L-carnitine

    500 mg tablet taken orally daily

  • Adefovir dipivoxilDrug

    120 mg tablet taken orally daily

  • Adefovir dipivoxil placeboDrug

    Oral placebo tablet taken daily

Study groups in NCT00001082
Study groupRoleWhat they receive
1ExperimentalParticipants will receive adefovir dipivoxil and L-carnitine
Receives: Drug: Levocarnitine; Drug: Adefovir dipivoxil
2ExperimentalParticipants will receive adefovir dipivoxil placebo and L-carnitine.
Receives: Drug: Levocarnitine; Drug: Adefovir dipivoxil placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Morbidity

    Measured: Throughout study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Aug 2001 (estimated)
  2. Study startDec 1996
  3. Primary completionJan 1999
  4. Study completionAug 1999

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Care provider
Enrolment
505 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00001082
Sponsor's protocol ID
CPCRA 039
Other IDs
11589
Status last verified
Sep 2013
First submitted
2 Nov 1999
Last updated
1 Oct 2013
Results posted
No

Publications

  • 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)

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Levocarnitine and Adefovir dipivoxil in people with Cytomegalovirus Infections and HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 15 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 45 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Oct 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 15 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Morbidity (time frame: Throughout study). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00001082, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2013.

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