To evaluate the effectiveness of atovaquone (566C80) compared to a standard antipneumocystis agent, (SMX/TMP), for the treatment of mild to moderate Pneumocystis carinii pneumonia (PCP) in AIDS patients. To compare the safety of short-term (21 days) treatment with 566C80 and SMX/TMP in AIDS patients with an acute episode of PCP. Standard therapies for acute treatment of PCP involve either SMX/TMP or pentamidine isetionate. Although both treatments are equally effective, side effects prevent completion of therapy in 11-55 percent of patients.

Condition	Treatment or Intervention	Phase
Pneumonia, Pneumocystis carinii HIV Infections	Drug: Atovaquone  Drug: Sulfamethoxazole-Trimethoprim	Phase II

Further Study Details: 

Expected Total Enrollment:  300

Standard therapies for acute treatment of PCP involve either SMX/TMP or pentamidine isetionate. Although both treatments are equally effective, side effects prevent completion of therapy in 11-55 percent of patients.

Patients are randomized into one of two treatment groups to receive either (1) 566C80 for 21 days, or (2) SMX/TMP for 21 days. Patients will be stratified according to severity of PCP. Group A will be those with an arterial-alveolar (A-a) DO2 < 35 mm Hg. Group B will have an A-a DO2 of 35-45 mm Hg., and will also be required to receive therapy with Corticosteroids. All doses are taken with food. During the 21 days of treatment, patients are examined clinically for adverse effects and have hematology (blood-related) and clinical chemistry studies conducted a minimum of 2 times weekly. More frequent monitoring may be required at the discretion of the investigator. To evaluate the effectiveness of study medication, the clinical status of each patient is evaluated 2 to 3 times per week (e.g., dyspnea score, cough score, chest tightness/pain score, vital signs). Also, on days 7 and 21 of treatment, an arterial blood gas measurement and chest X-ray are performed. Patients who experience severe toxicities will be discontinued from the study and placed on alternative therapy. Patients will also be removed from study if they show significant clinical deterioration within the first 7 days of therapy or if there is no improvement after 10 days of therapy. This study involves a double placebo with one group randomized to receive oral 566C80 and placebo tablets which look like SMX/TMP while the other group will receive SMX/TMP and placebo tablets looking like 566C80.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Patient must have the following:

• Presumptive diagnosis of AIDS as defined by the CDC.
• Untreated Pneumocystis carinii pneumonia (PCP).
• Willingness and ability to give informed consent.

Prior Medication: Allowed:

• Prophylactic therapy for Pneumocystis carinii pneumonia (PCP) including aerosolized pentamidine or sulfamethoxazole/trimethoprim (SMX/TMP) (at a dose no greater than two DS tablets twice daily).

Exclusion Criteria

Co-existing Condition: Patients with the following conditions or symptoms are excluded:

• Judged by the investigator to be in impending respiratory failure.
• Malabsorption or vomiting that would, in the judgment of investigator, potentially limit the retention and absorption of an oral therapy.
• Concurrent bacterial, fungal, or viral pneumonitis, pulmonary Kaposi's sarcoma or other concurrent illness, or chronic pulmonary disease that, in the investigator's opinion, would make interpretation of drug efficacy difficult.

Concurrent Medication: Excluded:

• Corticosteroid treatment (except replacement therapy or patients in Group B).
• Ganciclovir.
• Zidovudine (AZT).
• Investigational agents including antiretroviral agents (didanosine (ddI), dideoxycytidine (ddC), etc.).

Drugs likely to have anti-pneumocystis effect such as:

• Sulfonamides.
• Pentamidine.
• Dapsone.
• Trimethoprim.
• Other DHFR inhibitors.
• Primaquine.
• Clindamycin.
• Sulfonylureas.

Patients with the following are excluded:

• Judged by the investigator to be in impending respiratory failure.
• Prior therapy for this episode of PCP or treatment within 4 weeks of entry for a prior episode of PCP.
• Unable to or refuse to discontinue zidovudine, ganciclovir, or other antiretroviral agents during the 21 day treatment period.
• Unable to take medication orally or unwilling or unable to take study medication with food.
• Significant psychosis or emotional disorder such that, in the investigator's opinion, the patient would not be compliant with the study protocol.
• Prior documented glucose-6-phosphate dehydrogenase (G6PD) deficiency.
• Prior history of life-threatening toxicity to SMX/TMP such as severe rash or Stevens-Johnson syndrome.

Prior Medication: Excluded:

• Prior therapy for this episode of Pneumocystis carinii pneumonia (PCP) or treatment within 4 weeks for a prior episode of PCP.
• Blood transfusions.

Alabama
      Univ of Alabama at Birmingham, Birmingham,  Alabama,  35294,  United States
California
      Univ of California / San Diego Treatment Ctr, San Diego,  California,  921036325,  United States
      San Francisco Gen Hosp, San Francisco,  California,  941102859,  United States
      UCLA CARE Ctr, Los Angeles,  California,  90095,  United States
      Dr Richard Meyer, Los Angeles,  California,  90048,  United States
      USC, Los Angeles,  California,  90033,  United States
      UCSF - San Francisco Gen Hosp, San Francisco,  California,  94110,  United States
      Kaiser Foundation Hosp, Harbor City,  California,  90710,  United States
      Dr Marcus Conant, San Francisco,  California,  94115,  United States
      Infectious Disease Med Group, Oakland,  California,  94609,  United States
District of Columbia
      Georgetown Univ Med Ctr, Washington,  District of Columbia,  20007,  United States
      Veterans Administration Med Ctr, Washington,  District of Columbia,  20422,  United States
Georgia
      Dr Winkler Weinberg, Roswell,  Georgia,  30076,  United States
Maryland
      Johns Hopkins Univ School of Medicine, Baltimore,  Maryland,  21205,  United States
      Natl Inst of Allergy & Infect Dis / Cln Ctr, Bethesda,  Maryland,  20892,  United States
Missouri
      Washington Univ School of Medicine, St. Louis,  Missouri,  63108,  United States
New York
      Saint Vincent's Hosp and Med Ctr, New York,  New York,  10011,  United States
      Beth Israel Med Ctr / Peter Krueger Clinic, New York,  New York,  10003,  United States
      Harlem AIDS Treatment Group / Harlem Hosp Ctr, New York,  New York,  10037,  United States
North Carolina
      Duke Univ Med Ctr, Durham,  North Carolina,  27710,  United States
Ohio
      Univ of Cincinnati, Cincinnati,  Ohio,  452670405,  United States
Oregon
      Good Samaritan Hosp, Portland,  Oregon,  972103079,  United States
Pennsylvania
      Buckley Braffman Stern Med Associates, Philadelphia,  Pennsylvania,  19107,  United States
Tennessee
      The Regional Medical Ctr, Memphis, Memphis,  Tennessee,  38105,  United States
      Regional Med Ctr at Memphis, Memphis,  Tennessee,  38103,  United States
Texas
      Plaza Med Ctr, Houston,  Texas,  77004,  United States
      Baylor College of Medicine, Houston,  Texas,  77030,  United States
Belgium
      CHU Saint Pierre, Brussels,  Belgium
Canada, British Columbia
      Dr Julio S G Montaner, Vancouver,  British Columbia,  Canada
Canada, Ontario
      Wellesley Hosp, Toronto,  Ontario,  Canada
Canada, Quebec
      Montreal Gen Hosp, Montreal,  Quebec,  Canada
France
      Hopital Bichat - Claude Bernard, Paris,  France
Germany
      August-Viktoria-Krankenhaus Chefarst derII Inneren Abteilung, Berlin 41,  Germany
      Universitat Munchen / Medizinische Poliklinik, Munich 2,  Germany
Netherlands
      Natac Med Centre, Amsterdam,  Netherlands
Puerto Rico
      San Juan Veterans Administration Med Ctr, San Juan,  009275800,  Puerto Rico
United Kingdom
      Kobler Centre / Saint Stephen's Hosp, London,  United Kingdom
      Saint Mary's Hosp, London,  United Kingdom

Study chairs or principal investigators

Hughes WT,  Study Chair

Study ID Numbers:  ACTG 167; NIAID 90-CC-185; Protocol #03; FDA 53A; Project P71
Record last reviewed:  March 1992
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000655
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08