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

This study has been completed.
Sponsor:
Collaborator:
Glaxo Wellcome
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000655
First received: November 2, 1999
Last updated: February 25, 2011
Last verified: February 2011
  Purpose

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 Intervention Phase
Pneumonia, Pneumocystis Carinii
HIV Infections
Drug: Atovaquone
Drug: Sulfamethoxazole-Trimethoprim
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind Study of 566C80 Versus Septra (Trimethoprim/Sulfamethoxazole) for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 300
Primary Completion Date: January 1992 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000655

  Hide Study Locations
Locations
United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Kaiser Foundation Hosp
Harbor City, California, United States, 90710
UCLA CARE Ctr
Los Angeles, California, United States, 90095
USC
Los Angeles, California, United States, 90033
Dr Richard Meyer
Los Angeles, California, United States, 90048
Infectious Disease Med Group
Oakland, California, United States, 94609
Univ of California / San Diego Treatment Ctr
San Diego, California, United States, 921036325
UCSF - San Francisco Gen Hosp
San Francisco, California, United States, 94110
San Francisco Gen Hosp
San Francisco, California, United States, 941102859
Dr Marcus Conant
San Francisco, California, United States, 94115
United States, District of Columbia
Georgetown Univ Med Ctr
Washington, District of Columbia, United States, 20007
Veterans Administration Med Ctr
Washington, District of Columbia, United States, 20422
United States, Georgia
Dr Winkler Weinberg
Roswell, Georgia, United States, 30076
United States, Maryland
Johns Hopkins Univ School of Medicine
Baltimore, Maryland, United States, 21205
Natl Inst of Allergy & Infect Dis / Cln Ctr
Bethesda, Maryland, United States, 20892
United States, Missouri
Washington Univ School of Medicine
St Louis, Missouri, United States, 63108
United States, New York
Beth Israel Med Ctr / Peter Krueger Clinic
New York, New York, United States, 10003
Harlem AIDS Treatment Group / Harlem Hosp Ctr
New York, New York, United States, 10037
Saint Vincent's Hosp and Med Ctr
New York, New York, United States, 10011
United States, North Carolina
Duke Univ Med Ctr
Durham, North Carolina, United States, 27710
United States, Ohio
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
United States, Oregon
Good Samaritan Hosp
Portland, Oregon, United States, 972103079
United States, Pennsylvania
Buckley Braffman Stern Med Associates
Philadelphia, Pennsylvania, United States, 19107
United States, Tennessee
Regional Med Ctr at Memphis
Memphis, Tennessee, United States, 38103
The Regional Medical Ctr, Memphis
Memphis, Tennessee, United States, 38105
United States, Texas
Plaza Med Ctr
Houston, Texas, United States, 77004
Baylor College of Medicine
Houston, Texas, United States, 77030
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, Puerto Rico, 009275800
United Kingdom
Saint Mary's Hosp
London, United Kingdom
Kobler Centre / Saint Stephen's Hosp
London, United Kingdom
Sponsors and Collaborators
Glaxo Wellcome
Investigators
Study Chair: Hughes WT
  More Information

Additional Information:
Publications:
Hughes W, et al. Comparison of 566C80 & trimethoprim-sulfamethoxazole (TMP-SMZ) for the treatment of P. carinii pneumonitis (PCP). An International Multicenter, CCTG & ACTG Collaboration. Int Conf AIDS. 1992 Jul 19-24;8(1):We48 (abstract no WeB 1019)

ClinicalTrials.gov Identifier: NCT00000655     History of Changes
Other Study ID Numbers: ACTG 167, NIAID 90-CC-185, Protocol #03, FDA 53A, Project P71
Study First Received: November 2, 1999
Last Updated: February 25, 2011
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Trimethoprim-Sulfamethoxazole Combination
AIDS-Related Opportunistic Infections
Pneumonia, Pneumocystis carinii
Naphthoquinones
Antifungal Agents
Acquired Immunodeficiency Syndrome
Sulfamethoxazole-Trimethoprim

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Infection
Pneumonia
Pneumonia, Pneumocystis
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Lung Diseases
Lung Diseases, Fungal
Mycoses
Pneumocystis Infections
Respiratory Tract Diseases
Respiratory Tract Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Sulfamethoxazole
Trimethoprim
Trimethoprim-Sulfamethoxazole Combination
Anti-Infective Agents
Anti-Infective Agents, Urinary
Antimalarials
Antiparasitic Agents
Antiprotozoal Agents
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on October 22, 2014