A Randomized, Double-Blind Study of 566C80 Versus Septra (Sulfamethoxazole/Trimethoprim) for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients

A Randomized, Double-Blind Study of 566C80 Versus Septra (Trimethoprim/Sulfamethoxazole) for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients

Sponsors

Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator: Glaxo Wellcome

Source National Institute of Allergy and Infectious Diseases (NIAID)
Brief Summary

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.

Detailed Description

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.

Overall Status Completed
Primary Completion Date January 1992
Phase Phase 2
Study Type Interventional
Enrollment 300
Condition
Intervention

Intervention Type: Drug

Intervention Name: Atovaquone

Intervention Type: Drug

Intervention Name: Sulfamethoxazole-Trimethoprim

Eligibility

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.

Gender: All

Minimum Age: 13 Years

Maximum Age: N/A

Healthy Volunteers: No

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

Belgium

Canada

France

Germany

Netherlands

Puerto Rico

United Kingdom

United States

Verification Date

February 2011

Keywords
Has Expanded Access No
Condition Browse
Study Design Info

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Source: ClinicalTrials.gov