A Controlled Comparative Trial of Sulfamethoxazole-Trimethoprim Versus Aerosolized Pentamidine for Secondary Prophylaxis of Pneumocystis Carinii Pneumonia in AIDS Patients Receiving Azidothymidine (AZT)

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

A Controlled Comparative Trial of Trimethoprim - Sulfamethoxazole Versus Aerosolized Pentamidine for Secondary Prophylaxis of Pneumocystis Carinii Pneumonia in AIDS Patients Receiving Azidothymidine (AZT)

To determine if the drug combination sulfamethoxazole-trimethoprim (SMX-TMP), given by mouth, and the drug pentamidine (PEN), given by inhaled aerosol, are effective in preventing a relapse of Pneumocystis carinii pneumonia (PCP) when they are given to patients who have recovered from a first episode of PCP and are being given zidovudine (AZT) to treat primary HIV infection.

AZT prolongs survival in patients with AIDS and decreases the occurrence of opportunistic infections such as PCP. However, PCP recurs in about 43 percent of patients receiving AZT, indicating a need for other treatments to reduce the relapse rate.

The two medications to be tested in this study, SMX/TMP and aerosolized PEN, have also been partially effective in preventing recurrence of PCP. It is hoped that the combination of AZT with these medications will be more effective than AZT or one of the medications alone.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

AZT prolongs survival in patients with AIDS and decreases the occurrence of opportunistic infections such as PCP. However, PCP recurs in about 43 percent of patients receiving AZT, indicating a need for other treatments to reduce the relapse rate.

The two medications to be tested in this study, SMX/TMP and aerosolized PEN, have also been partially effective in preventing recurrence of PCP. It is hoped that the combination of AZT with these medications will be more effective than AZT or one of the medications alone.

Patients receive the standard dose of AZT at study entry. Low body weight patients receive AZT at a lower dose. Patients are randomly assigned to one of two medications intended to prevent the recurrence of PCP. Patients assigned to SMX/TMP will take 1 capsule which contains both drugs once a day for 1 year. Patients assigned to PEN will have 1 aerosol treatment every 4 weeks for 1 year. Blood will be drawn at intervals in order to estimate blood levels of the drugs and to detect any adverse effects from the drugs. Note: Earlier versions of this protocol reflect its original design as a 3-arm study comparing aerosolized PEN, SMX/TMP, and pyrimethamine-sulfadoxine as secondary prophylaxis of PCP in AIDS patients receiving AZT. In order to reduce the effective sample size and permit the completion of accrual in a reasonable period of time, the pyrimethamine - sulfadoxine arm of this study has been discontinued. Patients randomized to this arm will be continued in this study on the original randomized therapy. Management of these patients will follow that described for SMX/TMP in the latest protocol version. AMENDED: Lower dose of AZT allowed.

Study Type

Interventional

Enrollment

322

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

  • United States
    • California
      • Los Angeles, California, United States, 90033
        • USC CRS
      • San Diego, California, United States, 92103
        • Ucsd, Avrc Crs
      • San Francisco, California, United States, 94110
        • Ucsf Aids Crs
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana Univ. School of Medicine, Infectious Disease Research Clinic
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Bmc Actg Crs
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota, ACTU
    • New York
      • New York, New York, United States, 10021
        • Memorial Sloan-Kettering Cancer Ctr.
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case 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

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

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Patients must fulfill the following criteria:

  • Randomization within 10 weeks of completing therapy for Pneumocystis carinii pneumonia (PCP).
  • Ability to tolerate oral and aerosolized therapy at the time of randomization.
  • Life expectancy > 4 months.

Concurrent Medication:

Allowed:

  • Inhaled bronchodilators for cough and bronchospasm related to aerosolized pentamidine treatment.
  • Aspirin at modest doses.
  • Ibuprofen at modest doses.
  • Acetaminophen at modest doses.
  • Erythropoietin for management of anemia.
  • Allowed to treat opportunistic infections while on study:
  • Acyclovir.
  • Ketoconazole.
  • Amphotericin B.
  • Nystatin.
  • Clotrimazole.
  • Also allowed:
  • Ganciclovir (DHPG) for maintenance therapy of life-threatening or sight-threatening cytomegalovirus retinitis (CMV retinitis) infection only.
  • Zidovudine (AZT) must be discontinued during the acute induction phase of treatment and will be restarted when maintenance therapy is introduced.

Concurrent Treatment:

Allowed:

  • Local radiation therapy for Kaposi's sarcoma.

Prior Medication:

Allowed:

  • Primary prophylactic therapy prior to Pneumocystis carinii pneumonia (PCP) episode.

Risk Behavior:

Allowed:

  • Patients maintained in a methadone maintenance program per local investigator's judgment.

Exclusion Criteria

  • Active drug or alcohol abuse which would impair performance as a study subject.

Concurrent Medication:

Excluded:

  • Famotidine.
  • Any medications suspected of interference with the metabolism of zidovudine.
  • Flurazepam.
  • Chronic probenecid.
  • Phenobarbital.
  • Phenytoin.
  • Experimental therapies, except as noted.
  • Chronic oral bronchodilators should not be started in patients in order to maintain them on aerosolized pentamidine after they have exhibited pulmonary toxicity.

Prior Medication:

Excluded for the 30 patients who will undergo pharmacokinetic studies:

  • Zidovudine (AZT) at any time.
  • Excluded within 7 days of study entry for the 30 patients who will undergo pharmacokinetic studies:
  • Trimethoprim / sulfamethoxazole.
  • Pyrimethamine / sulfadoxine.
  • Aerosolized pentamidine.
  • Excluded:
  • Pentamidine by any route for the original infection.
  • Prophylactic therapy for Pneumocystis carinii pneumonia (PCP) between the discontinuation of acute treatment and study entry.

Prior Treatment:

Excluded within 2 weeks of study entry:

  • Transfusions of blood or red blood cells.

Patients may not have any of the following symptoms or diseases:

  • Known treatment-limiting hypersensitivity to sulfonamides, trimethoprim, pyrimethamine, pentamidine, or zidovudine (AZT), especially but not limited to, exfoliative dermatitis, erythema multiforme, and Stevens-Johnson syndrome.
  • Development of severe hypoglycemia (serum glucose < 50 mg/dl with pentamidine therapy).
  • History of neoplasms other than basal cell carcinoma of the skin or carcinoma in situ of the cervix, or mucocutaneous Kaposi's sarcoma.
  • Known visceral Kaposi's sarcoma.
  • Known glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.

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
  • Interventional Model: Parallel Assignment

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: Holzman 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)

August 1, 1991

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 3, 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 021
  • 10997 (Registry Identifier: 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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