A Comparative Study of a Combination of Zidovudine, Didanosine, and Double-Blinded Nevirapine Versus a Combination of Zidovudine and Didanosine

October 27, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

To assess the safety and toxicity of zidovudine (AZT)/didanosine (ddI) versus AZT/ddI combined with nevirapine in HIV-infected patients, and to obtain preliminary anti-HIV activity data using immunologic and virologic markers.

Previous in vitro studies suggest that HIV that has already developed resistance to AZT and ddI is less able to develop resistance to nevirapine, a non-nucleoside reverse transcriptase inhibitor. Thus, convergent combination therapy with these three drugs in HIV-infected patients may prove more effective.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Previous in vitro studies suggest that HIV that has already developed resistance to AZT and ddI is less able to develop resistance to nevirapine, a non-nucleoside reverse transcriptase inhibitor. Thus, convergent combination therapy with these three drugs in HIV-infected patients may prove more effective.

Patients are randomized to receive AZT/ddI plus either nevirapine or placebo daily for 48 weeks, with possible extension for at least 12 weeks. At eight participating sites, ACTG 808 and 809 will be conducted as virologic and pharmacokinetic substudies.

Study Type

Interventional

Enrollment

400

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Univ of Alabama at Birmingham
    • California
      • Los Angeles, California, United States, 900331079
        • Univ of Southern California / LA County USC Med Ctr
      • Oakland, California, United States, 946021018
        • Highland Gen Hosp / San Francisco Gen Hosp
      • Oakland, California, United States, 94609
        • Summitt Med Ctr / San Francisco Gen Hosp
      • San Diego, California, United States, 921036325
        • Univ of California / San Diego Treatment Ctr
      • San Francisco, California, United States, 941102859
        • San Francisco AIDS Clinic / San Francisco Gen Hosp
      • San Francisco, California, United States, 941102859
        • San Francisco Gen Hosp
    • Colorado
      • Denver, Colorado, United States, 80262
        • Univ of Colorado Health Sciences Ctr
    • Florida
      • Miami, Florida, United States, 331361013
        • Univ of Miami School of Medicine
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Northwestern Univ Med School
      • Chicago, Illinois, United States, 60612
        • Rush Presbyterian - Saint Luke's Med Ctr
      • Chicago, Illinois, United States, 60612
        • Cook County Hosp
    • Indiana
      • Indianapolis, Indiana, United States, 462025250
        • Indiana Univ Hosp
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Univ of Iowa Hosp and Clinic
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Harvard (Massachusetts Gen Hosp)
      • Boston, Massachusetts, United States, 02118
        • Boston Med Ctr
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess - West Campus
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Med Ctr
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Univ of Minnesota
      • Minneapolis, Minnesota, United States, 55415
        • Hennepin County Med Clinic
      • Saint Paul, Minnesota, United States, 55101
        • St Paul Ramsey Med Ctr
    • Nebraska
      • Omaha, Nebraska, United States, 681985130
        • Univ of Nebraska Med Ctr
    • New York
      • Bronx, New York, United States, 10461
        • Bronx Municipal Hosp Ctr/Jacobi Med Ctr
      • Bronx, New York, United States, 10465
        • Jack Weiler Hosp / Bronx Municipal Hosp
      • Bronx, New York, United States, 10467
        • Montefiore Med Ctr / Bronx Municipal Hosp
      • Bronx, New York, United States, 10461
        • Montefiore Drug Treatment Ctr / Bronx Municipal Hosp
      • Bronx, New York, United States, 10461
        • Montefiore Family Health Ctr / Bronx Municipal Hosp
      • Bronx, New York, United States, 10461
        • Samaritan Village Inc / Bronx Municipal Hosp
      • Bronx, New York, United States, 10467
        • North Central Bronx Hosp / Bronx Municipal Hosp
      • Bronx, New York, United States, 10461
        • Comprehensive Health Care Ctr / Bronx Municipal Hosp
      • Elmhurst, New York, United States, 11373
        • City Hosp Ctr at Elmhurst / Mount Sinai Hosp
      • New York, New York, United States, 10003
        • Beth Israel Med Ctr
      • New York, New York, United States, 10021
        • Cornell Univ Med Ctr
      • New York, New York, United States, 10021
        • Mem Sloan - Kettering Cancer Ctr
      • New York, New York, United States, 10029
        • Mount Sinai Med Ctr
      • New York, New York, United States, 10019
        • Saint Clare's Hosp and Health Ctr
    • North Carolina
      • Chapel Hill, North Carolina, United States, 275997215
        • Univ of North Carolina
      • Charlotte, North Carolina, United States, 28203
        • Carolinas Med Ctr
      • Greensboro, North Carolina, United States, 27401
        • Moses H Cone Memorial Hosp
      • Raleigh, North Carolina, United States, 27610
        • Wake County Dept of Health
    • Ohio
      • Cincinnati, Ohio, United States, 452670405
        • Univ of Cincinnati
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Univ of Pennsylvania at Philadelphia
      • Philadelphia, Pennsylvania, United States, 191075098
        • Thomas Jefferson Univ Hosp
      • Philadelphia, Pennsylvania, United States, 191046073
        • Girard Med Ctr

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Required:

  • PCP prophylaxis for patients with CD4 count < 200 cells/mm3 or a prior history of PCP.

Allowed:

  • Trimethoprim with sulfamethoxazole or dapsone, intravenous pentamidine, atovaquone, primaquine-clindamycin or trimetrexate for acute PCP.
  • Topical antifungals, clotrimazole, ketoconazole, fluconazole, and amphotericin B for treatment of mucosal and esophageal candidiasis.
  • Prophylaxis or therapy for opportunistic infections, as indicated, with other medications such as itraconazole, isoniazid, pyrazinamide, clofazimine, clarithromycin, azithromycin, ethambutol, amikacin, ciprofloxacin, ofloxacin, pyrimethamine, sulfadiazine, and clindamycin.
  • Maintenance therapy for opportunistic infections as long as patients have been on a stable dosage regimen for 1 month prior to study entry.
  • Ganciclovir for CMV retinitis or gastrointestinal disease as long as patients have been on a stable dose for at least 1 month prior to study entry with no grade 3 or 4 neutropenia or dependence on G-CSF.
  • Acyclovir (<= 1000 mg/day) for maintenance of herpes simplex virus infections.
  • Erythropoietin or G-CSF if clinically indicated.
  • Antibiotics for bacterial infections unless specifically excluded.
  • Rifampin or rifabutin.
  • Symptomatic treatments such as antipyretics, analgesics, and antiemetics.

Concurrent Treatment:

Allowed:

  • Local radiation therapy.

Prior Medication: Required:

  • At least 6 months of prior cumulative nucleoside therapy with AZT, ddI, or ddC, given as monotherapy or in combination.

Patients must have:

  • Prior or current documentation of HIV seropositivity by ELISA confirmed by Western blot, positive HIV antigen, or positive HIV culture, or a second antibody test by a method other than ELISA.
  • CD4 count <= 350 cells/mm3.
  • Prior cumulative nucleoside therapy of >= 6 months.
  • Consent of parent or guardian if less than 18 years of age.

Exclusion Criteria

Concurrent Medication:

Excluded:

  • Antiretroviral therapies other than study medications.
  • Systemic corticosteroids given consecutively for > 21 days.
  • Induction or maintenance with foscarnet.
  • Systemic cytotoxic chemotherapy for a malignancy.
  • Erythromycin.
  • Coumadin/warfarin.
  • Phenytoin or phenobarbital.
  • Amoxicillin/clavulanate acid (Augmentin) or ticarcillin/clavulanate acid (Timentin).

Patients with the following prior conditions are excluded:

  • History of pancreatitis.
  • History of intolerance to 500 or 600 mg/day AZT or to 400 mg/day ddI tablets or 500 mg/day ddI sachets.
  • History of grade 2 or worse peripheral neuropathy.

Prior Medication:

Excluded at any time:

Prior non-nucleoside reverse transcriptase inhibitors (NVP; L697,611; TIBO; atevirdine).

Excluded within 14 days prior to study entry:

  • Acute treatment for a serious infection or any opportunistic infection.
  • Biologic response modifiers such as interferon and IL-2.
  • Erythromycin.
  • Coumadin/warfarin.
  • Phenytoin or phenobarbital.
  • Ticarcillin/clavulanate acid (Timentin) or amoxicillin/clavulanate acid (Augmentin).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Masking: DOUBLE

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Bristol-Myers Squibb
Glaxo Wellcome

Investigators

  • Study Chair: D'Aquila R

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (ACTUAL)

November 1, 1994

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (ESTIMATE)

August 31, 2001

Study Record Updates

Last Update Posted (ACTUAL)

November 4, 2021

Last Update Submitted That Met QC Criteria

October 27, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 241
  • 11218 (DAIDS ES Registry Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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