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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000991
• Other study ID #: ACTG 081
• Secondary ID: 11056
• Status: Completed
• Phase: Phase 3
• Est. completion date: April 1994

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 600
• Est. completion date: April 1994
• Accepts healthy volunteers: No
• Gender: All
• Age group: 13 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• HIV Infections
• Infections
• Pneumonia
• Pneumonia, Pneumocystis
• Pneumonia, Pneumocystis Carinii

Intervention

Drug:
• Pentamidine isethionate

• Sulfamethoxazole-Trimethoprim

• Dapsone

• Zidovudine

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Tanzania, 

References & Publications (7)

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. — View Citation

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. — View Citation

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. — View Citation

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

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. — View Citation

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. — View Citation

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. — View Citation