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”

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.

Study Type: Interventional

Study Design: Treatment, Double-Blind

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.

Intervention(s) in this Clinical Trial

• Drug: Primaquine
• Drug: Sulfamethoxazole-Trimethoprim
• Drug: Dapsone
• Drug: Clindamycin

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).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 13 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Jacobus Pharmaceutical

Overall Clinical Trial Officials and Contacts

Safrin S Study Chair   

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00000640

Study ID Number: ACTG 108

ClinicalTrials.gov Identifier: NCT00000640

Health Authority: Unspecified

Click here for more information about Sulfamethoxazole-Trimethoprim