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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000655
• Other study ID #: ACTG 167
• Secondary ID: NIAID 90-CC-185P
• Status: Completed
• Phase: Phase 2
• First received: November 2, 1999
• Last updated: February 25, 2011

Study information

• Verified date: February 2011
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 300
• Est. primary completion date: January 1992
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 13 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• Pneumonia
• Pneumonia, Pneumocystis
• Pneumonia, Pneumocystis Carinii

Intervention

Drug:
• Atovaquone

• Sulfamethoxazole-Trimethoprim

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Glaxo Wellcome

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Netherlands,  Puerto Rico,  United Kingdom, 

References & Publications (2)

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. — View Citation

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