A Comparison of Atovaquone and Pentamidine in the Prevention of Pneumocystis Carinii Pneumonia in HIV-Infected Patients Who Cannot Take TMP/SMX

NCT ID: NCT00002340

Last Updated: 2005-06-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 615 participants
• Study Classification: INTERVENTIONAL

Brief Summary

To assess whether high dose or low dose atovaquone suspension is more effective than aerosolized pentamidine as prophylaxis against Pneumocystis carinii pneumonia (PCP) in high-risk HIV-infected patients. To compare the safety of chronic administration of the three regimens in patients with advanced HIV disease. To determine the relationship between steady state atovaquone plasma concentrations and prophylactic efficacy against PCP.

Detailed Description

Patients are randomized to receive oral atovaquone at 1 of 2 doses once daily or aerosolized pentamidine once every 4 weeks. Treatment continues until 18 months after the last patient is enrolled. Patients are stratified into primary or secondary prophylaxis strata based on prior occurrence of a PCP episode.

Conditions

Pneumonia, Pneumocystis Carinii; HIV Infections

Study Design

• Primary Study Purpose: TREATMENT

Interventions

Atovaquone

Intervention Type: DRUG

Pentamidine isethionate

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• Antimicrobial agents not specifically prohibited.

Concurrent Treatment:

Allowed:

• Transfusion.

Patients must have:

• HIV positivity.
• Prior PCP (histologically confirmed) OR documented CD4 count < 200 cells/mm3 OR constitutional symptoms such as thrush or unexplained fever (> 100 F) for 2 or more weeks.
• No current or suspected active PCP, and no signs of active PCP on chest x-ray.
• Prior intolerance to TMP/SMX or other trimethoprim or sulfa-containing regimens.
• Life-expectancy of at least 6 months.

NOTE:

• Pregnant women are eligible at the discretion of the investigator.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Significant psychosis or emotional disorder that would preclude study compliance.
• Severe chronic diarrhea (e.g., > five stools/day) that may negatively affect absorption of oral medication.
• Unable to take oral medication or unable or unwilling to take medication with food.

Concurrent Medication:

Excluded:

• Rifampin.
• Other investigational agents except for drugs available through Treatment INDs or expanded access programs.
• Medications likely to have anti-pneumocystis effect (e.g., dapsone, trimethoprim, pyrimethamine, trimetrexate, other DHFR inhibitors, sulfadiazine, sulfamethoxazole, other sulfonamides, primaquine, clindamycin, and sulfonylureas.
• Corticosteroids in greater than physiologic replacement doses for more than 21 consecutive days.
• Systemic therapy for CNS toxoplasmosis, Kaposi's sarcoma, lymphoma, other active malignancies, or other disease that may decrease life expectancy or confound assessment.

Patients with the following prior conditions are excluded:

• History of severe or intractable intolerance to atovaquone or aerosolized pentamidine.
• Prior hypoglycemia, pancreatitis, arrhythmias, or severe hypotension associated with any form of pentamidine.
• Prior enrollment in this protocol. Active substance abuse that would preclude study compliance.

• Minimum Eligible Age: 13 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Glaxo Wellcome

INDUSTRY

Sponsor Role: lead

Locations

Goodgame Med Group

Maitland, Florida, United States

Bay Area AIDS Consortium

Tampa, Florida, United States

Saint Vincent's Hosp and Med Ctr

New York, New York, United States

Holmes Hosp

Cincinnati, Ohio, United States

Hampton Roads Med Specialists

Hampton, Virginia, United States

Countries

United States

References

Chan C, Montaner J, Lefebvre EA, Morey G, Dohn M, McIvor RA, Scott J, Marina R, Caldwell P. Atovaquone suspension compared with aerosolized pentamidine for prevention of Pneumocystis carinii pneumonia in human immunodeficiency virus-infected subjects intolerant of trimethoprim or sulfonamides. J Infect Dis. 1999 Aug;180(2):369-76. doi: 10.1086/314893.

Reference Type: BACKGROUND

PMID: 10395851 (View on PubMed)

Other Identifiers

230

Identifier Type: -

Identifier Source: secondary_id

227B

Identifier Type: -

Identifier Source: org_study_id