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
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
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: Jacobus Pharmaceutical Official(s) and/or principal investigator(s):
Safrin S, Study Chair
Black JR, Study Chair
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.
Clinical Details
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: Treatment, Double-Blind
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
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).
Locations and Contacts
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
Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States
Georgetown Univ Med Ctr, Washington, District of Columbia 20007, United States
Univ of Hawaii, Honolulu, Hawaii 96816, United States
Rush Presbyterian - Saint Luke's Med Ctr, Chicago, Illinois 60612, United States
Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States
Methodist Hosp of Indiana / Life Care Clinic, Indianapolis, Indiana 46202, United States
Louisiana State Univ Med Ctr / Tulane Med School, New Orleans, Louisiana 70112, United States
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
Univ of Minnesota, Minneapolis, Minnesota 55455, United States
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
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
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 Health Sciences Univ / Children's Hosp of Los Angeles, Portland, Oregon 97201, United States
Univ of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
Hemophilia Ctr of Western PA / Univ of Pittsburgh, Pittsburgh, Pennsylvania 15219, United States
Julio Arroyo, West Columbia, South Carolina 29169, United States
Univ of Texas Galveston, Galveston, Texas 775550435, United States
Additional Information
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: June 23, 2005
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