A Phase III Comparative Study of Dapsone / Trimethoprim and Clindamycin / Primaquine Versus Sulfamethoxazole / Trimethoprim in the Treatment of Mild-to-Moderate PCP in Patients With AIDS

Condition(s) targeted: Pneumonia, Pneumocystis Carinii; HIV Infections

Intervention: Primaquine (Drug); Sulfamethoxazole-Trimethoprim (Drug); Dapsone (Drug); Clindamycin (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Safrin S, Study Chair
Black JR, Study Chair

To evaluate the effectiveness of two oral treatments for mild to moderate Pneumocystis carinii pneumonia (PCP): dapsone/trimethoprim or clindamycin/primaquine as compared to a standard treatment program of sulfamethoxazole/trimethoprim (SMX/TMP) to assess the tolerance of these two alternative treatments as compared to the standard treatment of SMX/TMP. Per 09/09/92 amendment, to assess the efficacy and tolerance of these two alternative treatments in patients who are intolerant to SMX/TMP. The type of treatment being studied has the advantages of wide applicability throughout the world (including developing countries) and low cost. An oral treatment is more accessible to patients than drugs given by injection or by inhalation.

Official title: A Phase III Comparative Study of Dapsone / Trimethoprim and Clindamycin / Primaquine Versus Trimethoprim / Sulfamethoxazole in the Treatment of Mild-to-Moderate PCP in Patients With AIDS

Study design: Masking: Double-Blind, Primary Purpose: Treatment

Detailed description: The type of treatment being studied has the advantages of wide applicability throughout the world (including developing countries) and low cost. An oral treatment is more accessible to patients than drugs given by injection or by inhalation. Patients with confirmed PCP are randomized into one of three treatment groups. Group A receives SMX/TMP. Half of group A receives dapsone placebo (placebo is an inactive substance) daily plus trimethoprim placebo; the other half receives clindamycin placebo plus primaquine placebo. Group B is given dapsone plus trimethoprim. Half of group B receives SMX/TMP placebo; the other half receives clindamycin placebo plus primaquine placebo. Group C is given clindamycin plus primaquine. Half of group C receives SMX/TMP placebo, the other half receives dapsone placebo plus trimethoprim placebo. Treatment lasts 21 days; dosages will be adjusted for patients weighing less than 50 kg and more than 80 kg. Patients with a history of intolerance to SMX/TMP for whom rechallenge is considered medically contraindicated may be randomized to one of the non-sulfamethoxazole-containing arms.

Minimum age: 13 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria Concurrent Medication: Allowed:

- Erythropoietin.

- Maintenance treatment with investigational triazoles (e. g., itraconazole).

- Antiemetics for nausea/vomiting, antihistamines for rash/pruritus, antipyretics for

systemic symptoms (fever, headache, etc.) should be used for treatment of symptoms.

- Nonsteroidal antiinflammatory agents may be used for control of myalgias, headache,

etc. Concurrent Treatment: Allowed:

- Blood transfusions.

Patients must have the following:

- Pneumocystis carinii pneumonia.

- HIV infection.

- Willing and able to sign informed consent. Patients under 18 years of age may enter

with consent of parent or guardian. Prior Medication: Allowed:

- Up to 24 hours of treatment with sulfamethoxazole/trimethoprim (SMX/TMP), dapsone /

trimethoprim, or clindamycin / primaquine, or one dose of pentamidine for this episode of Pneumocystis carinii pneumonia (PCP).

- Prior PCP prophylaxis.

Required:

- Adjunctive prednisone therapy in patients with (A-a) DO2 of 35 - 45 torr receiving

acute anti-PCP treatment. Exclusion Criteria Co-existing Condition: Patients with the following conditions and diseases are excluded: Positive screen for glucose-6-phosphate dehydrogenase deficiency.

- Known NAD methemoglobin reductase deficiency and/or known hemoglobin M abnormality.

Concurrent Medication: Excluded:

- Zidovudine (AZT).

- Ganciclovir.

- GM-CSF or G-CSF. Rifampin.

- Rifabutin.

- Corticosteroids (in patients with baseline (A-a) DO2 < 35 torr). Investigational

drugs not specifically allowed.

- Folinic acid.

Patients with the following are excluded:

- Previous dose-limiting intolerance to sulfones, trimethoprim, clindamycin, or

primaquine. Requirement for other medications potentially effective in the treatment of Pneumocystis carinii pneumonia (PCP) (e. g., pyrimethamine and sulfadiazine).

- Prior enrollment in ACTG 108. Presence of other concurrent pulmonary pathology that

would make interpretation of response to antipneumocystis therapy difficult. Inability to take oral therapy. Prior Medication: Excluded:

- Acute treatment doses of anti-Pneumocystis carinii pneumonia agents within 30 days

prior to study entry except as noted above.

- Systemic steroids above adrenal replacement doses within 7 days prior to study entry

(except for patients with (A-a) DO2 of 35 - 45 torr who receive prednisone in

conjunction with acute anti-PCP treatment).

USC CRS, Los Angeles, California 90033, United States

Stanford CRS, Palo Alto, California, United States

Ucsf Aids Crs, San Francisco, California, United States

Santa Clara Valley Med. Ctr., San Jose, California, United States

San Mateo County AIDS Program, San Mateo, California, United States

Harbor-UCLA Med. Ctr. CRS, Torrance, California 90502, United States

University of Colorado Hospital CRS, Aurora, Colorado, United States

Univ. of Hawaii at Manoa, Leahi Hosp., Honolulu, Hawaii 96816, United States

Northwestern University CRS, Chicago, Illinois, United States

Rush Univ. Med. Ctr. ACTG CRS, Chicago, Illinois 60612, United States

Indiana Univ. School of Medicine, Infectious Disease Research Clinic, Indianapolis, Indiana 46202, United States

Methodist Hosp. of Indiana, Indianapolis, Indiana 46202, United States

Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU, New Orleans, Louisiana 70112, United States

Johns Hopkins Adult AIDS CRS, Baltimore, Maryland, United States

Beth Israel Deaconess - East Campus A0102 CRS, Boston, Massachusetts 02215, United States

Massachusetts General Hospital ACTG CRS, Boston, Massachusetts 02114, United States

University of Minnesota, ACTU, Minneapolis, Minnesota 55455, United States

Washington U CRS, St. Louis, Missouri, United States

SUNY - Buffalo, Erie County Medical Ctr., Buffalo, New York 14215, United States

Beth Israel Med. Ctr. (Mt. Sinai), New York, New York 10003, United States

Cornell University A2201, New York, New York 10021, United States

NY Univ. HIV/AIDS CRS, New York, New York 10016, United States

NYU Med. Ctr., Dept. of Medicine, New York, New York, United States

Univ. of Rochester ACTG CRS, Rochester, New York 14642, United States

Unc Aids Crs, Chapel Hill, North Carolina 27599, United States

Carolinas HealthCare System, Carolinas Med. Ctr., Charlotte, North Carolina 28203, United States

Regional Center for Infectious Disease, Wendover Medical Center CRS, Greensboro, North Carolina, United States

Univ. of Cincinnati CRS, Cincinnati, Ohio, United States

Case CRS, Cleveland, Ohio 44106, United States

The Ohio State Univ. AIDS CRS, Columbus, Ohio 43210, United States

Pitt CRS, Pittsburgh, Pennsylvania 15213, United States

University of Washington AIDS CRS, Seattle, Washington, United States

Click here for more information about Sulfamethoxazole-Trimethoprim

Related publications:

Wu AW, Gray S, Brookmeyer R, Safrin S. Quality of life in a double-blind randomized trial of 3 oral regimens for mild-to-moderate Pneumocystis carinii pneumonia in AIDS (ACTG 108). Int Conf AIDS. 1996 Jul 7-12;11(1):229 (abstract no TuB112)

Safrin S, Finkelstein DM, Feinberg J, Frame P, Simpson G, Wu A, Cheung T, Soeiro R, Hojczyk P, Black JR. Comparison of three regimens for treatment of mild to moderate Pneumocystis carinii pneumonia in patients with AIDS. A double-blind, randomized, trial of oral trimethoprim-sulfamethoxazole, dapsone-trimethoprim, and clindamycin-primaquine. ACTG 108 Study Group. Ann Intern Med. 1996 May 1;124(9):792-802.

Rubin HR, Wu AW, Gutierrez M, Liriano O, Safrin S. Spanish translation of a functional status questionnaire for Pneumocystis carinii pneumonia. Int Conf AIDS. 1992 Jul 19-24;8(2):B178 (abstract no PoB 3549)

Last updated: March 29, 2012