Clinical trial NCT00000640: 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
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumonia, Pneumocystis Carinii
HIV Infections
Keywords: Trimethoprim-Sulfamethoxazole Combination
Pneumonia, Pneumocystis carinii
Primaquine
Dapsone
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
Clindamycin
Sulfamethoxazole-Trimethoprim
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Jacobus Pharmaceutical
name: Glaxo Wellcome
First posted: 2001-08-31
Enrollment: 290
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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).

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: USC CRS
state: California
city: Palo Alto
country: United States
facility: Stanford CRS
state: California
city: San Francisco
country: United States
facility: Ucsf Aids Crs
state: California
city: San Jose
country: United States
facility: Santa Clara Valley Med. Ctr.
state: California
city: San Mateo
country: United States
facility: San Mateo County AIDS Program
state: California
city: Torrance
country: United States
facility: Harbor-UCLA Med. Ctr. CRS
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Honolulu
country: United States
facility: Univ. of Hawaii at Manoa, Leahi Hosp.
state: Hawaii
city: Chicago
country: United States
facility: Rush Univ. Med. Ctr. ACTG CRS
state: Illinois
city: Chicago
country: United States
facility: Northwestern University CRS
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ. School of Medicine, Infectious Disease Research Clinic
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Hosp. of Indiana
state: Indiana
city: New Orleans
country: United States
facility: Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins Adult AIDS CRS
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital ACTG CRS
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess - East Campus A0102 CRS
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota, ACTU
state: Minnesota
city: Saint Louis
country: United States
facility: Washington U CRS
state: Missouri
city: Buffalo
country: United States
facility: SUNY - Buffalo, Erie County Medical Ctr.
state: New York
city: New York
country: United States
facility: Beth Israel Med. Ctr. (Mt. Sinai)
state: New York
city: New York
country: United States
facility: NY Univ. HIV/AIDS CRS
state: New York
city: New York
country: United States
facility: Cornell University A2201
state: New York
city: New York
country: United States
facility: NYU Med. Ctr., Dept. of Medicine
state: New York
city: Rochester
country: United States
facility: Univ. of Rochester ACTG CRS
state: New York
city: Chapel Hill
country: United States
facility: Unc Aids Crs
state: North Carolina
city: Charlotte
country: United States
facility: Carolinas HealthCare System, Carolinas Med. Ctr.
state: North Carolina
city: Greensboro
country: United States
facility: Regional Center for Infectious Disease, Wendover Medical Center CRS
state: North Carolina
city: Cincinnati
country: United States
facility: Univ. of Cincinnati CRS
state: Ohio
city: Cleveland
country: United States
facility: Case CRS
state: Ohio
city: Columbus
country: United States
facility: The Ohio State Univ. AIDS CRS
state: Ohio
city: Pittsburgh
country: United States
facility: Pitt CRS
state: Pennsylvania
city: Seattle
country: United States
facility: University of Washington AIDS CRS
state: Washington
Study officials:
name: Safrin S
role: STUDY_CHAIR
name: Black JR
role: STUDY_CHAIR
References:
citation: 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)
citation: 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. doi: 10.7326/0003-4819-124-9-199605010-00003.
citation: 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)