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A Comparison of Atovaquone and Pentamidine in the Prevention of Pneumocystis Carinii Pneumonia in HIV-Infected Patients Who Cannot Take TMP/SMX
This study has been completed.
First Received: November 2, 1999   Last Updated: June 23, 2005   History of Changes
Sponsored by: Glaxo Wellcome
Information provided by: NIH AIDS Clinical Trials Information Service
ClinicalTrials.gov Identifier: NCT00002340
  Purpose

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 Intervention Phase
Pneumonia, Pneumocystis Carinii
HIV Infections
Drug: Atovaquone
Drug: Pentamidine isethionate
Phase III

Study Type: Interventional
Study Design: Treatment, Safety Study
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

Resource links provided by NLM:


Further study details as provided by NIH AIDS Clinical Trials Information Service:

Estimated Enrollment: 615
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

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00002340

Locations
United States, Florida
Goodgame Med Group
Maitland, Florida, United States, 32751
Bay Area AIDS Consortium
Tampa, Florida, United States, 33609
United States, New York
Saint Vincent's Hosp and Med Ctr
New York, New York, United States, 10011
United States, Ohio
Holmes Hosp
Cincinnati, Ohio, United States, 452670405
United States, Virginia
Hampton Roads Med Specialists
Hampton, Virginia, United States, 23666
Sponsors and Collaborators
Glaxo Wellcome
  More Information

Publications:
Study ID Numbers: 227B, 230
Study First Received: November 2, 1999
Last Updated: June 23, 2005
ClinicalTrials.gov Identifier: NCT00002340     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by NIH AIDS Clinical Trials Information Service:
Pneumonia, Pneumocystis carinii
Pentamidine
Antifungal Agents
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
atovaquone

Study placed in the following topic categories:
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Pneumocystosis
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Immunologic Deficiency Syndromes
Virus Diseases
Antimalarials
Mycoses
Pneumonia, Pneumocystis
Atovaquone
Pneumocystis Infections
Respiratory Tract Diseases
Respiratory Tract Infections
HIV Infections
Antifungal Agents
Lung Diseases
Sexually Transmitted Diseases
Pentamidine
Retroviridae Infections
Pneumonia
Lung Diseases, Fungal

Additional relevant MeSH terms:
Trypanocidal Agents
Communicable Diseases
Anti-Infective Agents
Antiprotozoal Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Infection
Antimalarials
Pneumonia, Pneumocystis
Mycoses
Antiparasitic Agents
Respiratory Tract Diseases
Respiratory Tract Infections
Therapeutic Uses
Antifungal Agents
Pentamidine
Retroviridae Infections
Lung Diseases, Fungal
RNA Virus Infections
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Pharmacologic Actions
Immunologic Deficiency Syndromes
Virus Diseases
Pneumocystis Infections
Atovaquone
HIV Infections
Lung Diseases

ClinicalTrials.gov processed this record on September 01, 2009