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

Sponsor

Glaxo Wellcome (Industry)

Overall Status

Completed

CT.gov ID

NCT00002340

Collaborator

(none)

615

Enrollment

Locations

123

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia, Pneumocystis Carinii HIV Infections	Drug: Atovaquone Drug: Pentamidine isethionate	Phase 3

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

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

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Goodgame Med Group	Maitland	Florida	United States	32751
2	Bay Area AIDS Consortium	Tampa	Florida	United States	33609
3	Saint Vincent's Hosp and Med Ctr	New York	New York	United States	10011
4	Holmes Hosp	Cincinnati	Ohio	United States	452670405
5	Hampton Roads Med Specialists	Hampton	Virginia	United States	23666