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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.
First Received: November 2, 1999   Last Updated: August 22, 2008   History of Changes
Sponsors and Collaborators: Jacobus Pharmaceutical
National Institute of Allergy and Infectious Diseases (NIAID)
Glaxo Wellcome
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000640
  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 III

Study Type: Interventional
Study Design: Treatment, Double-Blind
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
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000640

  Show 42 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)
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)

Study ID Numbers: ACTG 108
Study First Received: November 2, 1999
Last Updated: August 22, 2008
ClinicalTrials.gov Identifier: NCT00000640     History of Changes
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

Study placed in the following topic categories:
Sexually Transmitted Diseases, Viral
Clindamycin
Trimethoprim
Primaquine
Folate
Trimethoprim-Sulfamethoxazole Combination
Vitamin B9
Pneumonia, Pneumocystis
Mycoses
Anti-Bacterial Agents
Antimalarials
Respiratory Tract Infections
Respiratory Tract Diseases
Dapsone
Retroviridae Infections
Lung Diseases, Fungal
Clindamycin-2-phosphate
Sulfamethoxazole
Acquired Immunodeficiency Syndrome
Anti-Infective Agents, Urinary
Folinic Acid
Folic Acid Antagonists
Immunologic Deficiency Syndromes
Virus Diseases
Folic Acid
Pneumocystis Infections
HIV Infections
Lung Diseases
Sexually Transmitted Diseases
Pneumonia

Additional relevant MeSH terms:
Anti-Infective Agents
Antiprotozoal Agents
Trimethoprim
Sexually Transmitted Diseases, Viral
Clindamycin
Slow Virus Diseases
Primaquine
Molecular Mechanisms of Pharmacological Action
Trimethoprim-Sulfamethoxazole Combination
Renal Agents
Infection
Antimalarials
Anti-Bacterial Agents
Pneumonia, Pneumocystis
Mycoses
Antiparasitic Agents
Respiratory Tract Diseases
Respiratory Tract Infections
Therapeutic Uses
Dapsone
Retroviridae Infections
Lung Diseases, Fungal
RNA Virus Infections
Immune System Diseases
Clindamycin-2-phosphate
Sulfamethoxazole
Acquired Immunodeficiency Syndrome
Anti-Infective Agents, Urinary
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on July 02, 2009