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

This study has been completed.
Sponsor:
Collaborators:
Jacobus Pharmaceutical
Glaxo Wellcome
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000640
First received: November 2, 1999
Last updated: March 29, 2012
Last verified: March 2012
  Purpose

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 Intervention Phase
Pneumonia, Pneumocystis Carinii
HIV Infections
Drug: Primaquine
Drug: Sulfamethoxazole-Trimethoprim
Drug: Dapsone
Drug: Clindamycin
Phase 3

Study Type: Interventional
Study Design: Masking: Double-Blind
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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 290
Study Completion Date: September 1994
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

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000640

  Show 32 Study Locations
Sponsors and Collaborators
Jacobus Pharmaceutical
Glaxo Wellcome
Investigators
Study Chair: Safrin S
Study Chair: Black JR
  More Information

Additional Information:
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)
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)

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000640     History of Changes
Other Study ID Numbers: ACTG 108, 11083
Study First Received: November 2, 1999
Last Updated: March 29, 2012
Health Authority: Unspecified

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Trimethoprim-Sulfamethoxazole Combination
Pneumonia, Pneumocystis carinii
Primaquine
Dapsone
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
Clindamycin
Sulfamethoxazole-Trimethoprim

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Pneumonia
Pneumonia, Pneumocystis
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Lung Diseases, Fungal
Mycoses
Pneumocystis Infections
Clindamycin
Clindamycin-2-phosphate
Dapsone
Primaquine
Sulfamethoxazole
Trimethoprim
Trimethoprim-Sulfamethoxazole Combination
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 24, 2014