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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000991
First received: November 2, 1999
Last updated: March 28, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
Pneumonia, Pneumocystis Carinii
HIV Infections
Drug: Pentamidine isethionate
Drug: Sulfamethoxazole-Trimethoprim
Drug: Dapsone
Drug: Zidovudine
Phase 3

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Trial of Three Anti-Pneumocystis Agents Plus Zidovudine for the Primary Prevention of Serious Infections in Patients With Advanced HIV Infection

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 600
Study Completion Date: April 1994
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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000991

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

Additional Information:
Publications:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000991     History of Changes
Other Study ID Numbers: ACTG 081, 11056
Study First Received: November 2, 1999
Last Updated: March 28, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Trimethoprim-Sulfamethoxazole Combination
Toxoplasmosis
AIDS-Related Opportunistic Infections
Pneumonia, Pneumocystis carinii
Pentamidine
Dapsone
Drug Evaluation
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
Zidovudine
Sulfamethoxazole-Trimethoprim

Additional relevant MeSH terms:
Infection
Communicable Diseases
HIV Infections
Acquired Immunodeficiency Syndrome
Pneumonia
Pneumonia, Pneumocystis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Lung Diseases, Fungal
Mycoses
Pneumocystis Infections
Zidovudine
Sulfamethoxazole
Trimethoprim
Pentamidine
Trimethoprim-Sulfamethoxazole Combination
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors

ClinicalTrials.gov processed this record on September 22, 2014