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

NCT ID: NCT00000991

Last Updated: 2021-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

600 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1994-04-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Pneumonia, Pneumocystis Carinii HIV Infections

Keywords

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Trimethoprim-Sulfamethoxazole Combination Toxoplasmosis AIDS-Related Opportunistic Infections Pneumonia, Pneumocystis carinii Pentamidine Dapsone Drug Evaluation Drug Therapy, Combination Acquired Immunodeficiency Syndrome Zidovudine Sulfamethoxazole-Trimethoprim

Study Design

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Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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Pentamidine isethionate

Intervention Type DRUG

Sulfamethoxazole-Trimethoprim

Intervention Type DRUG

Dapsone

Intervention Type DRUG

Zidovudine

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

13 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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S Bozzette

Role: STUDY_CHAIR

S Spector

Role: STUDY_CHAIR

Locations

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USC CRS

Los Angeles, California, United States

Site Status

Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.

Oakland, California, United States

Site Status

Ucsd, Avrc Crs

San Diego, California, United States

Site Status

Univ. of Miami AIDS CRS

Miami, Florida, United States

Site Status

Chicago Children's CRS

Chicago, Illinois, United States

Site Status

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, United States

Site Status

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital ACTG CRS

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess - East Campus A0102 CRS

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, United States

Site Status

University of Minnesota, ACTU

Minneapolis, Minnesota, United States

Site Status

Washington U CRS

St Louis, Missouri, United States

Site Status

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, United States

Site Status

Univ. of Rochester ACTG CRS

Rochester, New York, United States

Site Status

Unc Aids Crs

Chapel Hill, North Carolina, United States

Site Status

Duke Univ. Med. Ctr. Adult CRS

Durham, North Carolina, United States

Site Status

Case CRS

Cleveland, Ohio, United States

Site Status

The Ohio State Univ. AIDS CRS

Columbus, Ohio, United States

Site Status

Pitt CRS

Pittsburgh, Pennsylvania, United States

Site Status

University of Washington AIDS CRS

Seattle, Washington, United States

Site Status

Mbeya Med. Research Program, Mbeya Referral Hosp. CRS

Mbeya, , Tanzania

Site Status

Countries

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United States Tanzania

References

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Bozzette SA, Hays RD, Berry SH, Kanouse DE. A Perceived Health Index for use in persons with advanced HIV disease: derivation, reliability, and validity. Med Care. 1994 Jul;32(7):716-31. doi: 10.1097/00005650-199407000-00005.

Reference Type BACKGROUND
PMID: 8028406 (View on PubMed)

Bozzette SA, Finkelstein DM, Spector SA, Frame P, Powderly WG, He W, Phillips L, Craven D, van der Horst C, Feinberg J. A randomized trial of three antipneumocystis agents in patients with advanced human immunodeficiency virus infection. NIAID AIDS Clinical Trials Group. N Engl J Med. 1995 Mar 16;332(11):693-9. doi: 10.1056/NEJM199503163321101.

Reference Type BACKGROUND
PMID: 7854375 (View on PubMed)

Glick ME. CTG studies yield results. AIDS Clinical Trials Group. NIAID AIDS Agenda. 1995 Spring:8-9.

Reference Type BACKGROUND
PMID: 11362451 (View on PubMed)

Justice AC, Rabeneck L, Hays RD, Wu AW, Bozzette SA. Sensitivity, specificity, reliability, and clinical validity of provider-reported symptoms: a comparison with self-reported symptoms. Outcomes Committee of the AIDS Clinical Trials Group. J Acquir Immune Defic Syndr. 1999 Jun 1;21(2):126-33.

Reference Type BACKGROUND
PMID: 10360804 (View on PubMed)

Justice AC, Holmes W, Gifford AL, Rabeneck L, Zackin R, Sinclair G, Weissman S, Neidig J, Marcus C, Chesney M, Cohn SE, Wu AW; Adult AIDS Clinical Trials Unit Outcomes Committee. Development and validation of a self-completed HIV symptom index. J Clin Epidemiol. 2001 Dec;54 Suppl 1:S77-90. doi: 10.1016/s0895-4356(01)00449-8.

Reference Type BACKGROUND
PMID: 11750213 (View on PubMed)

Ioannidis JP, Dixon DO, McIntosh M, Albert JM, Bozzette SA, Schnittman SM. Relationship between event rates and treatment effects in clinical site differences within multicenter trials: an example from primary Pneumocystis carinii prophylaxis. Control Clin Trials. 1999 Jun;20(3):253-66. doi: 10.1016/s0197-2456(98)00053-1.

Reference Type BACKGROUND
PMID: 10357498 (View on PubMed)

DiRienzo AG, van Der Horst C, Finkelstein DM, Frame P, Bozzette SA, Tashima KT. Efficacy of trimethoprim-sulfamethoxazole for the prevention of bacterial infections in a randomized prophylaxis trial of patients with advanced HIV infection. AIDS Res Hum Retroviruses. 2002 Jan 20;18(2):89-94. doi: 10.1089/08892220252779629.

Reference Type BACKGROUND
PMID: 11839141 (View on PubMed)

Other Identifiers

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11056

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 081

Identifier Type: -

Identifier Source: org_study_id