Clinical trial NCT00002340: A Comparison of Atovaquone and Pentamidine in the Prevention of Pneumocystis Carinii Pneumonia in HIV-Infected Patients Who Cannot Take TMP/SMX
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumonia, Pneumocystis Carinii
HIV Infections
Keywords: Pneumonia, Pneumocystis carinii
Pentamidine
Antifungal Agents
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
atovaquone
Lead sponsor: NIH AIDS Clinical Trials Information Service
Sponsor class: INDUSTRY
First posted: 2001-08-31
Enrollment: 615
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Maitland
country: United States
facility: Goodgame Med Group
state: Florida
city: Tampa
country: United States
facility: Bay Area AIDS Consortium
state: Florida
city: New York
country: United States
facility: Saint Vincent's Hosp and Med Ctr
state: New York
city: Cincinnati
country: United States
facility: Holmes Hosp
state: Ohio
city: Hampton
country: United States
facility: Hampton Roads Med Specialists
state: Virginia
Study officials:
References:
citation: 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.