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

HIV Infections Clinical Trial

Official title:

A Randomized, Open-Label Trial of High Dose Atovaquone Versus Low Dose Atovaquone Versus Aerosolized Pentamidine for Prophylaxis of Pneumocystis Carinii Pneumonia in Patients With HIV Infection Who Are Intolerant of TMP/SMX

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00002340
• Other study ID #: 227B
• Secondary ID: 230
• Status: Completed
• Phase: Phase 3
• First received: November 2, 1999
• Last updated: June 23, 2005

Study information

• Verified date: August 1997
• Source: NIH AIDS Clinical Trials Information Service
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 615
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Drug:
• Atovaquone

• Pentamidine isethionate

Locations

Country	Name	City	State
United States	Holmes Hosp	Cincinnati	Ohio
United States	Hampton Roads Med Specialists	Hampton	Virginia
United States	Goodgame Med Group	Maitland	Florida
United States	Saint Vincent's Hosp and Med Ctr	New York	New York
United States	Bay Area AIDS Consortium	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Glaxo Wellcome

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation