A Randomized, Double-Blind Study of 566C80 Versus Septra (Sulfamethoxazole/Trimethoprim) for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pneumonia, Pneumocystis Carinii; HIV Infections
Intervention: Atovaquone (Drug); Sulfamethoxazole-Trimethoprim (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Hughes WT, Study Chair
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.
Clinical Details
Official title: A Randomized, Double-Blind Study of 566C80 Versus Septra (Trimethoprim/Sulfamethoxazole) for the Treatment of Pneumocystis Carinii Pneumonia in AIDS Patients
Study design: Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Primary Purpose: Treatment
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
Minimum age: 13 Years.
Maximum age: N/A.
Gender(s): 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.
Locations and Contacts
CHU Saint Pierre, Brussels, Belgium
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
Univ of Alabama at Birmingham, Birmingham, Alabama 35294, United States
Dr Julio S G Montaner, Vancouver, British Columbia, Canada
Kaiser Foundation Hosp, Harbor City, California 90710, United States
Dr Richard Meyer, Los Angeles, California 90048, United States
UCLA CARE Ctr, Los Angeles, California 90095, United States
USC, Los Angeles, California 90033, United States
Infectious Disease Med Group, Oakland, California 94609, United States
Univ of California / San Diego Treatment Ctr, San Diego, California 921036325, United States
Dr Marcus Conant, San Francisco, California 94115, United States
San Francisco Gen Hosp, San Francisco, California 941102859, United States
UCSF - San Francisco Gen Hosp, San Francisco, California 94110, 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
Harlem AIDS Treatment Group / Harlem Hosp Ctr, New York, New York 10037, United States
Saint Vincent's Hosp and Med Ctr, New York, New York 10011, United States
Duke Univ Med Ctr, Durham, North Carolina 27710, United States
Univ of Cincinnati, Cincinnati, Ohio 452670405, United States
Wellesley Hosp, Toronto, Ontario, Canada
Good Samaritan Hosp, Portland, Oregon 972103079, United States
Buckley Braffman Stern Med Associates, Philadelphia, Pennsylvania 19107, United States
Montreal Gen Hosp, Montreal, Quebec, Canada
Regional Med Ctr at Memphis, Memphis, Tennessee 38103, United States
The Regional Medical Ctr, Memphis, Memphis, Tennessee 38105, United States
Baylor College of Medicine, Houston, Texas 77030, United States
Plaza Med Ctr, Houston, Texas 77004, United States
Additional Information
Click here for more information about Sulfamethoxazole-Trimethoprim
Related 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) Hughes W, Leoung G, Kramer F, Bozzette SA, Safrin S, Frame P, Clumeck N, Masur H, Lancaster D, Chan C, et al. Comparison of atovaquone (566C80) with trimethoprim-sulfamethoxazole to treat Pneumocystis carinii pneumonia in patients with AIDS. N Engl J Med. 1993 May 27;328(21):1521-7.
Last updated: February 25, 2011
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