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

NCT00000991 | Completed Phase 3

• 2 other identifiers: ACTG 08111056
• Study Type: interventional
• Target: 600
• Locations: 2 countries
• Sites: 21

Brief Summary

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.

Conditions

Pneumonia, Pneumocystis Carinii; HIV Infections

Keywords

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

Interventions

Pentamidine isethionate DRUG

Sulfamethoxazole-Trimethoprim DRUG

Dapsone DRUG

Zidovudine DRUG

Eligibility Criteria

• Age: 13 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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:

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (21)

USC CRS

Los Angeles, California, 90033, United States

Location

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

Oakland, California, 94609, United States

Location

Ucsd, Avrc Crs

San Diego, California, 92103, United States

Location

Univ. of Miami AIDS CRS

Miami, Florida, 33136, United States

Location

Chicago Children's CRS

Chicago, Illinois, 60614, United States

Location

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, 46202, United States

Location

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital ACTG CRS

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess - East Campus A0102 CRS

Boston, Massachusetts, 02215, United States

Location

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, 02215, United States

Location

University of Minnesota, ACTU

Minneapolis, Minnesota, 55455, United States

Location

Washington U CRS

St Louis, Missouri, United States

Location

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, 14215, United States

Location

Univ. of Rochester ACTG CRS

Rochester, New York, United States

Location

Unc Aids Crs

Chapel Hill, North Carolina, United States

Location

Duke Univ. Med. Ctr. Adult CRS

Durham, North Carolina, United States

Location

Case CRS

Cleveland, Ohio, 44106, United States

Location

The Ohio State Univ. AIDS CRS

Columbus, Ohio, 43210, United States

Location

Pitt CRS

Pittsburgh, Pennsylvania, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98105, United States

Location

Mbeya Med. Research Program, Mbeya Referral Hosp. CRS

Mbeya, Tanzania

Location

Related Publications (7)

• 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.

  PMID: 8028406 BACKGROUND

• 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.

  PMID: 7854375 BACKGROUND

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

  PMID: 11362451 BACKGROUND

• 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.

  PMID: 10360804 BACKGROUND

• 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.

  PMID: 11750213 BACKGROUND

• 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.

  PMID: 10357498 BACKGROUND

• 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.

  PMID: 11839141 BACKGROUND

MeSH Terms

Conditions

Pneumonia, Pneumocystis; HIV Infections; Toxoplasmosis; AIDS-Related Opportunistic Infections; Acquired Immunodeficiency Syndrome

Interventions

Pentamidine; Trimethoprim, Sulfamethoxazole Drug Combination; Dapsone; Zidovudine

Condition Hierarchy (Ancestors)

Lung Diseases, Fungal; Mycoses; Bacterial Infections and Mycoses; Infections; Pneumocystis Infections; Respiratory Tract Infections; Pneumonia; Lung Diseases; Respiratory Tract Diseases; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Coccidiosis; Protozoan Infections; Parasitic Diseases; Opportunistic Infections; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Benzamidines; Amidines; Organic Chemicals; Sulfamethoxazole; Benzenesulfonamides; Sulfonamides; Amides; Sulfanilamides; Aniline Compounds; Amines; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Trimethoprim; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Drug Combinations; Pharmaceutical Preparations; Thymidine; Pyrimidine Nucleosides; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• S Bozzette

  STUDY CHAIR

• S Spector

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Masking: NONE
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: April 1, 1994
• Last Updated: November 4, 2021

Record last verified: 2021-10

Locations

US (20); TA (1)