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.

Condition	Treatment or Intervention	Phase
Pneumonia, Pneumocystis carinii HIV Infections	Drug: Primaquine  Drug: Sulfamethoxazole-Trimethoprim  Drug: Dapsone  Drug: Clindamycin	Phase III

Further Study Details: 

Expected Total Enrollment:  290

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.

Ages Eligible for Study:  13 Years and above,  Genders Eligible for Study:  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).

California
      San Francisco Veterans Administration Med Ctr, San Francisco,  California,  94121,  United States
      Univ of Southern California / LA County USC Med Ctr, Los Angeles,  California,  900331079,  United States
      Harbor UCLA Med Ctr, Torrance,  California,  90502,  United States
Colorado
      Univ of Colorado Health Sciences Ctr, Denver,  Colorado,  80262,  United States
District of Columbia
      Georgetown Univ Med Ctr, Washington,  District of Columbia,  20007,  United States
Hawaii
      Univ of Hawaii, Honolulu,  Hawaii,  96816,  United States
Illinois
      Rush Presbyterian - Saint Luke's Med Ctr, Chicago,  Illinois,  60612,  United States
Indiana
      Indiana Univ Hosp, Indianapolis,  Indiana,  462025250,  United States
      Methodist Hosp of Indiana / Life Care Clinic, Indianapolis,  Indiana,  46202,  United States
Louisiana
      Louisiana State Univ Med Ctr / Tulane Med School, New Orleans,  Louisiana,  70112,  United States
Massachusetts
      Harvard (Massachusetts Gen Hosp), Boston,  Massachusetts,  02114,  United States
      Beth Israel Deaconess Med Ctr, Boston,  Massachusetts,  02215,  United States
      Baystate Med Ctr of Springfield, Springfield,  Massachusetts,  01199,  United States
      Univ of Massachusetts Med Ctr, Worcester,  Massachusetts,  01655,  United States
Minnesota
      Univ of Minnesota, Minneapolis,  Minnesota,  55455,  United States
New York
      Montefiore Drug Treatment Ctr / Bronx Municipal Hosp, Bronx,  New York,  10461,  United States
      Montefiore Family Health Ctr / Bronx Municipal Hosp, Bronx,  New York,  10461,  United States
      Samaritan Village Inc / Bronx Municipal Hosp, Bronx,  New York,  10461,  United States
      Nassau County Med Ctr, East Meadow,  New York,  11554,  United States
      SUNY - Stony Brook, Stony Brook,  New York,  117948153,  United States
      Univ of Rochester Medical Center, Rochester,  New York,  14642,  United States
      Bellevue Hosp / New York Univ Med Ctr, New York,  New York,  10016,  United States
      Jack Weiler Hosp / Bronx Municipal Hosp, Bronx,  New York,  10465,  United States
      Cornell Univ Med Ctr, New York,  New York,  10021,  United States
      Saint Luke's - Roosevelt Hosp Ctr, New York,  New York,  10025,  United States
      Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx,  New York,  10461,  United States
      Montefiore Med Ctr / Bronx Municipal Hosp, Bronx,  New York,  10467,  United States
      SUNY / Erie County Med Ctr at Buffalo, Buffalo,  New York,  14215,  United States
      Beth Israel Med Ctr, New York,  New York,  10003,  United States
      SUNY / Health Sciences Ctr at Brooklyn, Brooklyn,  New York,  112032098,  United States
      North Central Bronx Hosp / Bronx Municipal Hosp, Bronx,  New York,  10467,  United States
North Carolina
      Carolinas Med Ctr, Charlotte,  North Carolina,  28203,  United States
      Univ of North Carolina, Chapel Hill,  North Carolina,  275997215,  United States
      Moses H Cone Memorial Hosp, Greensboro,  North Carolina,  27401,  United States
Ohio
      Case Western Reserve Univ, Cleveland,  Ohio,  44106,  United States
      Ohio State Univ Hosp Clinic, Columbus,  Ohio,  432101228,  United States
      Med College of Ohio, Toledo,  Ohio,  43699,  United States
Oregon
      Oregon Health Sciences Univ / Children's Hosp of Los Angeles, Portland,  Oregon,  97201,  United States
Pennsylvania
      Univ of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States
      Hemophilia Ctr of Western PA / Univ of Pittsburgh, Pittsburgh,  Pennsylvania,  15219,  United States
South Carolina
      Julio Arroyo, West Columbia,  South Carolina,  29169,  United States
Texas
      Univ of Texas Galveston, Galveston,  Texas,  775550435,  United States

Study chairs or principal investigators

Safrin S,  Study Chair
Black JR,  Study Chair

Study ID Numbers:  ACTG 108
Record last reviewed:  January 2003
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000640
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2005-04-08