The Effectiveness of Three Drug Combinations in HIV-Infected Patients Who Have Taken Zidovudine for More Than 12 Weeks

October 28, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Phase II Randomized Study of the Virologic and Immunologic Effects of d4T vs Zidovudine Plus d4T vs Zidovudine Plus Ddl in HIV-Infected Patients With CD4 Cell Counts Between 300-600/mm3 and Greater Than 12 Weeks Zidovudine Experience

To compare the effect of stavudine (d4T) alone or with zidovudine (AZT) versus didanosine (ddI) alone or with AZT on CD4 counts, HIV RNA levels, and viral load in HIV-infected patients [AS PER AMENDMENT 3/21/97: To compare the effects of d4T alone versus ddI alone versus AZT plus ddI]. To compare the safety of d4T/AZT. AS PER AMENDMENT 3/21/97: To evaluate the pharmacokinetic interactions of AZT and d4T both at an extracellular and intracellular level.

Although AZT and ddI can delay the advancement of HIV disease, the benefit of either of these drugs has proven to be only temporary. d4T, a new nucleoside analog with a favorable toxicity profile and demonstrated activity against HIV, offers an additional therapeutic option. It is reasonably assumed that the benefit of an antiretroviral agent in terms of delaying clinical disease progression is directly related to its ability to achieve and sustain viral suppression; thus, this study measures effects on viral load and CD4 count.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Although AZT and ddI can delay the advancement of HIV disease, the benefit of either of these drugs has proven to be only temporary. d4T, a new nucleoside analog with a favorable toxicity profile and demonstrated activity against HIV, offers an additional therapeutic option. It is reasonably assumed that the benefit of an antiretroviral agent in terms of delaying clinical disease progression is directly related to its ability to achieve and sustain viral suppression; thus, this study measures effects on viral load and CD4 count.

Patients are randomized in a blinded fashion to receive AZT or placebo in combination with open-label d4T or ddI for up to 48 weeks. AS PER AMENDMENT 3/21/97: The study is now composed of three arms: open-label d4T versus open-label ddI plus blinded AZT placebo versus blinded AZT plus open-label ddI. Patients originally assigned to the d4T + AZT arm, which was closed 10/96, will be given the option of discontinuing AZT and remaining on d4T monotherapy or discontinuing all study drugs. In addition, all study participants will be asked to participate in a pharmacology substudy.

Study Type

Interventional

Enrollment

200

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

  • Puerto Rico
      • San Juan, Puerto Rico
        • Puerto Rico-AIDS CRS
      • San Juan, Puerto Rico, 00936
        • San Juan City Hosp. PR NICHD CRS
  • United States
    • California
      • Los Angeles, California, United States, 90095
        • UCLA CARE Center CRS
      • Palo Alto, California, United States, 94115
        • Stanford CRS
      • San Diego, California, United States, 92103
        • Ucsd, Avrc Crs
      • San Francisco, California, United States, 94110
        • Ucsf Aids Crs
      • Torrance, California, United States, 90502
        • Harbor-UCLA Med. Ctr. CRS
    • Colorado
      • Aurora, Colorado, United States, 80262
        • University of Colorado Hospital CRS
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's National Med. Ctr., ACTU
    • Florida
      • Jacksonville, Florida, United States, 32209
        • Univ. of Florida Jacksonville NICHD CRS
      • Miami, Florida, United States, 33136
        • Univ. of Miami AIDS CRS
    • Hawaii
      • Honolulu, Hawaii, United States, 96816
        • Univ. of Hawaii at Manoa, Leahi Hosp.
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Cook County Hosp. CORE Ctr.
      • Chicago, Illinois, United States, 60611
        • Northwestern University CRS
      • Chicago, Illinois, United States, 60612
        • Rush Univ. Med. Ctr. ACTG CRS
      • Chicago, Illinois, United States
        • Weiss Memorial Hosp.
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana Univ. School of Medicine, Infectious Disease Research Clinic
      • Indianapolis, Indiana, United States, 46202
        • Methodist Hosp. of Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana Univ. School of Medicine, Wishard Memorial
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
        • Tulane Hemophilia Treatment Ctr.
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital ACTG CRS
      • Boston, Massachusetts, United States, 02118
        • Bmc Actg Crs
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Med. Ctr., ACTG CRS
    • Minnesota
      • Minneapolis, Minnesota, United States, 55415
        • Hennepin County Med. Ctr., Div. of Infectious Diseases
      • Minneapolis, Minnesota, United States
        • University of Minnesota, ACTU
    • Missouri
      • Saint Louis, Missouri, United States
        • Washington U CRS
      • Saint Louis, Missouri, United States, 63112
        • St. Louis ConnectCare, Infectious Diseases Clinic
    • New York
      • Brooklyn, New York, United States, 11203
        • SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS
      • Buffalo, New York, United States, 14215
        • SUNY - Buffalo, Erie County Medical Ctr.
      • Rochester, New York, United States, 14642
        • Univ. of Rochester ACTG CRS
    • Ohio
      • Cincinnati, Ohio, United States
        • Univ. of Cincinnati CRS
      • Columbus, Ohio, United States, 43210
        • The Ohio State Univ. AIDS CRS
    • Washington
      • Seattle, Washington, United States, 98122
        • University of Washington AIDS CRS

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

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Required for patients whose CD4 count falls below 200 cells/mm3:

  • PCP prophylaxis with TMP/SMX, aerosolized pentamidine, or dapsone.

Allowed:

  • Atovaquone, IV pentamidine, trimethoprim-dapsone, clindamycin-primaquine, trimetrexate, or TMP/SMX for acute PCP.
  • Topical antifungals, clotrimazole, ketoconazole, fluconazole, and amphotericin B for mucosal and esophageal candidiasis.
  • Itraconazole.
  • Amphotericin B.
  • Rifabutin.
  • Isoniazid.
  • Pyrazinamide.
  • Clofazimine.
  • Clarithromycin.
  • Azithromycin.
  • Ethambutol.
  • Amikacin.
  • Ciprofloxacin.
  • Ofloxacin.
  • Pyrimethamine.
  • Sulfadiazine.
  • Clindamycin.
  • Ganciclovir.
  • G-CSF.
  • Acyclovir (up to 1000 mg/day).
  • Erythropoietin.
  • Antibiotics for bacterial infections.
  • Antipyretics.
  • Analgesics.
  • Antiemetics.
  • Rifampin.

Concurrent Treatment:

Allowed:

  • Local radiation therapy.

Patients must have:

  • HIV infection.
  • CD4 count 300-600 cells/mm3.
  • More than 12 weeks (was 24 weeks, AMENDED 3/31/96) of total prior AZT ( > 500 mg/day without serious adverse event). Subjects must be actively taking ZDV for at least 4 continuous weeks up to the time of study entry.
  • No prior or current history of AIDS.
  • No active opportunistic infection.
  • Life expectancy of at least 2 years.
  • Consent of patient and parent or guardian if less than 18 years of age.

NOTE:

  • Protocol is approved for prisoner enrollment.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

  • Malignancy requiring systemic cytotoxic chemotherapy.
  • Serious underlying medical condition other than HIV that would reduce life expectancy to < 2 years.

Concurrent Medication:

Excluded:

  • Antiretrovirals other than study drugs.
  • Foscarnet.

Patients with the following prior conditions are excluded:

  • Unexplained temperature >= 38.5 C for 7 days or chronic diarrhea (>= three stools daily) for 15 days, if occurring within 30 days prior to study entry.
  • History of acute or chronic pancreatitis.
  • History of grade 2 or higher peripheral neuropathy.
  • History of grade 3 or worse intolerance to 500-600 mg/day AZT.

Prior Medication:

Excluded:

(within 30 days prior to study entry)

  • Prior ddI, ddC, 3TC or d4T (more than 2 weeks total).
  • Non-nucleoside reverse transcriptase inhibitor or protease inhibitor.
  • Biologic response modifiers such as interferon and IL-2.
  • Other experimental therapy.

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

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

Investigators

  • Study Chair: Havlir D
  • Study Chair: Richman D
  • Study Chair: Pollard R
  • Study Chair: Friedland G

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, 1997

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 28, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 290
  • 11266 (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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