A Study of Three Drugs Plus Zidovudine in the Prevention of Infections in HIV-Infected Patients

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

A Randomized Trial of Three Anti-Pneumocystis Agents Plus Zidovudine for the Primary Prevention of Serious Infections in Patients With Advanced HIV Infection

To evaluate and compare 3 anti-pneumocystis regimens plus zidovudine (AZT) in persons with HIV infection and T4 cell count less than 200 cells/mm3. All persons completing at least 8 weeks of therapy on 081 will be offered the opportunity to participate in the nested study (ACTG 981) of systemic antifungal therapy (fluconazole) versus local therapy (Clotrimazole) for the prevention of serious fungal disease.

Persons with HIV disease who are receiving AZT are at risk for PCP, toxoplasmosis, bacterial pneumonia, and other serious infections. It is therefore important to find drugs that can be given along with AZT to control these infections. Aerosolized pentamidine (PEN) has been shown to be useful in preventing PCP and is expected to lower the 2-year risk of PCP. Both sulfamethoxazole/trimethoprim (SMX/TMP) and dapsone probably also provide effective preventive treatment against PCP, and both may be useful in preventing toxoplasmosis and extrapulmonary pneumocystosis.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Persons with HIV disease who are receiving AZT are at risk for PCP, toxoplasmosis, bacterial pneumonia, and other serious infections. It is therefore important to find drugs that can be given along with AZT to control these infections. Aerosolized pentamidine (PEN) has been shown to be useful in preventing PCP and is expected to lower the 2-year risk of PCP. Both sulfamethoxazole/trimethoprim (SMX/TMP) and dapsone probably also provide effective preventive treatment against PCP, and both may be useful in preventing toxoplasmosis and extrapulmonary pneumocystosis.

All patients receive AZT. In addition, they are placed in one of three groups to receive either SMX/TMP, dapsone, or PEN. Stratification criteria are:

Received first AZT equal to or less than 6 weeks prior to study entry. Received first AZT more than 6 weeks prior to study entry. Potential to participate in ACTG 981. ACTG center in which the patient is enrolled.

Study Type

Interventional

Enrollment

600

Phase

  • Phase 3

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

  • Tanzania
      • Mbeya, Tanzania
        • Mbeya Med. Research Program, Mbeya Referral Hosp. CRS
  • United States
    • California
      • Los Angeles, California, United States, 90033
        • USC CRS
      • Oakland, California, United States, 94609
        • Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.
      • San Diego, California, United States, 92103
        • Ucsd, Avrc Crs
    • Florida
      • Miami, Florida, United States, 33136
        • Univ. of Miami AIDS CRS
    • Illinois
      • Chicago, Illinois, United States, 60614
        • Chicago Children's CRS
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana Univ. School of Medicine, Infectious Disease Research Clinic
    • Maryland
      • Baltimore, Maryland, United States, 21287
        • Johns Hopkins Adult AIDS CRS
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital ACTG CRS
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Med. Ctr., ACTG CRS
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess - East Campus A0102 CRS
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota, ACTU
    • Missouri
      • Saint Louis, Missouri, United States
        • Washington U CRS
    • New York
      • Buffalo, New York, United States, 14215
        • SUNY - Buffalo, Erie County Medical Ctr.
      • Rochester, New York, United States
        • Univ. of Rochester ACTG CRS
    • North Carolina
      • Chapel Hill, North Carolina, United States
        • Unc Aids Crs
      • Durham, North Carolina, United States
        • Duke Univ. Med. Ctr. Adult CRS
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case CRS
      • Columbus, Ohio, United States, 43210
        • The Ohio State Univ. AIDS CRS
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States
        • Pitt CRS
    • Washington
      • Seattle, Washington, United States, 98105
        • 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

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

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Antifolate medication required to treat an intercurrent infection.
  • Treatment of intercurrent infections or malignancies.
  • Fluconazole.
  • Itraconazole.
  • Standard or investigational therapy for pneumocystosis (PCP) or toxoplasmosis.
  • Only the forms of primary prophylaxis for PCP or toxoplasmosis assigned to the participant under the protocol. Patients who develop intolerance to all forms of prophylaxis assigned in this protocol or who develop PCP or toxoplasmosis may receive alternate or investigation forms of prophylaxis with or without zidovudine but must continue to be followed under this protocol.
  • Discouraged but allowed: AL-721.
  • Chronic acyclovir.
  • Ketoconazole.
  • Amphotericin B.
  • Corticosteroids at greater than physiologic replacement doses are strongly discouraged.
  • They should be used as briefly as possible and only for definite specific indications.

Patient must conform to the following:

  • Receiving or candidates for zidovudine therapy at least 500 mg/day under current labeled indications with no history of pneumocystosis (PCP) or toxoplasmosis.
  • Evidence of HIV infection documented by HIV antibody tests.
  • T4 cell count less than 200 cells/mm3 at any time prior to study entry.
  • Willing to sign informed consent.
  • Willing to be followed by a participating ACTG center for duration of the study.
  • Allowed: Concurrent enrollment in long-term follow-up studies in previously blinded trials of AZT (ACTG 016 and 019).

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions are excluded:

  • History of documented or presumed pneumocystosis (PCP) or toxoplasmosis.
  • Active bacterial or mycobacterial infection.
  • History of type I hypersensitivity, exfoliative rash, or rash with mucosal involvement, severe bronchospasm, or other life-threatening reaction to any of the study drugs or to other sulfas, sulfones, or pentamidine.
  • History of intolerance causing dose interruption while receiving zidovudine at equal to or less than 600 mg/day or causing dose reduction to less than 500 mg/day within 4 weeks prior to entry.
  • Advanced Kaposi's sarcoma or other malignancy not specifically allowed that has been rapidly progressive during the month prior to enrollment or which may be expected to require chemotherapy within 90 days of study entry.

Concurrent Medication:

Excluded:

  • Active primary treatment for an infection or malignancy.
  • Other form of antifolate medication not specifically allowed.
  • Other antiretroviral or biologic response modifier.
  • Ganciclovir, if it causes intolerance to AZT equal to or more than 500 mg/day.
  • Foscarnet.

Patients with the following are excluded:

  • Symptoms and conditions defined in Exclusion Coexisting Conditions.
  • Glucose 6-phosphate dehydrogenase deficiency (GPD).
  • History of pneumocystosis (PCP) or toxoplasmosis.
  • History of type I hypersensitivity, exfoliative rash, or rash with mucosal involvement, severe bronchospasm, or other life-threatening reaction to any of the study drugs or to other sulfas, sulfones, or pentamidine.
  • History of intolerance causing dose interruption while receiving zidovudine at equal to or less than 500 mg/day with 4 weeks pior to study entry.

Prior Medication:

Excluded within 4 weeks of study entry:

  • Any other form of pneumocystosis (PCP) chemoprophylaxis.
  • Active substance abuse, including alcohol.

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: None (Open Label)

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)

Investigators

  • Study Chair: S Bozzette
  • Study Chair: S Spector

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 Start

December 7, 2022

Primary Completion

December 7, 2022

Study Completion (Actual)

April 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 28, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 081
  • 11056 (DAIDS ES Registry Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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