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

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Completed

CT.gov ID

NCT00000640

Collaborator

Jacobus Pharmaceutical (Industry), Glaxo Wellcome (Industry)

290

Enrollment

Locations

9.1

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Pneumonia, Pneumocystis Carinii HIV Infections	Drug: Primaquine Drug: Sulfamethoxazole-Trimethoprim Drug: Dapsone Drug: Clindamycin	Phase 3

Detailed Description

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.

Study Design

Study Type:

Interventional

Masking:

Double

Primary Purpose:

Treatment

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

Actual Study Completion Date :

Sep 1, 1994

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

13 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	USC CRS	Los Angeles	California	United States	90033
2	Stanford CRS	Palo Alto	California	United States
3	Ucsf Aids Crs	San Francisco	California	United States
4	Santa Clara Valley Med. Ctr.	San Jose	California	United States
5	San Mateo County AIDS Program	San Mateo	California	United States
6	Harbor-UCLA Med. Ctr. CRS	Torrance	California	United States	90502
7	University of Colorado Hospital CRS	Aurora	Colorado	United States
8	Univ. of Hawaii at Manoa, Leahi Hosp.	Honolulu	Hawaii	United States	96816
9	Rush Univ. Med. Ctr. ACTG CRS	Chicago	Illinois	United States	60612
10	Northwestern University CRS	Chicago	Illinois	United States
11	Indiana Univ. School of Medicine, Infectious Disease Research Clinic	Indianapolis	Indiana	United States	46202
12	Methodist Hosp. of Indiana	Indianapolis	Indiana	United States	46202
13	Tulane Med. Ctr. - Charity Hosp. of New Orleans, ACTU	New Orleans	Louisiana	United States	70112
14	Johns Hopkins Adult AIDS CRS	Baltimore	Maryland	United States
15	Massachusetts General Hospital ACTG CRS	Boston	Massachusetts	United States	02114
16	Beth Israel Deaconess - East Campus A0102 CRS	Boston	Massachusetts	United States	02215
17	University of Minnesota, ACTU	Minneapolis	Minnesota	United States	55455
18	Washington U CRS	Saint Louis	Missouri	United States
19	SUNY - Buffalo, Erie County Medical Ctr.	Buffalo	New York	United States	14215
20	Beth Israel Med. Ctr. (Mt. Sinai)	New York	New York	United States	10003
21	NY Univ. HIV/AIDS CRS	New York	New York	United States	10016
22	Cornell University A2201	New York	New York	United States	10021
23	NYU Med. Ctr., Dept. of Medicine	New York	New York	United States
24	Univ. of Rochester ACTG CRS	Rochester	New York	United States	14642
25	Unc Aids Crs	Chapel Hill	North Carolina	United States	27599
26	Carolinas HealthCare System, Carolinas Med. Ctr.	Charlotte	North Carolina	United States	28203
27	Regional Center for Infectious Disease, Wendover Medical Center CRS	Greensboro	North Carolina	United States
28	Univ. of Cincinnati CRS	Cincinnati	Ohio	United States
29	Case CRS	Cleveland	Ohio	United States	44106
30	The Ohio State Univ. AIDS CRS	Columbus	Ohio	United States	43210
31	Pitt CRS	Pittsburgh	Pennsylvania	United States	15213
32	University of Washington AIDS CRS	Seattle	Washington	United States