Gradual Initiation of Sulfamethoxazole/Trimethoprim as Primary Pneumocystis Carinii Pneumonia Prophylaxis

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 4

Conditions: Pneumonia, Pneumocystis Carinii; HIV Infections

Treatments: Drug: Sulfamethoxazole-Trimethoprim

Study type: Interventional

Funder types: Industry; NIH

Identifiers

NCT00000816

11244 (Registry Identifier)

ACTG 268

Details and patient eligibility

About

To determine whether gradual initiation of sulfamethoxazole/trimethoprim (SMX/TMP) reduces the incidence of treatment-limiting adverse reactions compared to the routine initiation of the drugs for Pneumocystis carinii pneumonia (PCP) prophylaxis in HIV-infected patients.

Although a number of clinical trials have demonstrated the superiority of SMX/TMP for PCP prophylaxis, the incidence of adverse reactions to this medication is high. In a pilot study in which patients were initiated with SMX/TMP prophylaxis by gradually increasing the dose over 2 weeks, no significant adverse reactions have occurred.

Full description

Although a number of clinical trials have demonstrated the superiority of SMX/TMP for PCP prophylaxis, the incidence of adverse reactions to this medication is high. In a pilot study in which patients were initiated with SMX/TMP prophylaxis by gradually increasing the dose over 2 weeks, no significant adverse reactions have occurred.

Patients are randomized to receive either gradually increasing doses of SMX/TMP suspension or routine daily initiation of SMX/TMP double strength (DS) tablets for 2 weeks. All patients will then be switched over to receive open-label SMX/TMP DS tablets daily for 10 weeks.

Sex: All

Ages: 13+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

Concurrent Medication:

Allowed if clinically indicated:

• Recombinant erythropoietin (rEPO) and G-CSF.

Allowed for symptomatic treatment of mild study drug toxicity:

• Antipyretics and analgesics (ibuprofen).
• Antihistamines (diphenhydramine HCl).
• Terfenadine or astemizole (but not allowed with concomitant antifungal or macrolide use).
• Systemic steroids.

Patients must have:

• HIV infection.
• CD4 count <= 250 cells/mm3 OR history or presence of thrush.
• No history of confirmed or probable pneumocystosis.

NOTE:

• Pregnant women are not excluded, but safety issues should be discussed with patient prior to enrollment.
• This study is appropriate for prisoner participation.
• Coenrollment in ongoing ACTG antiretroviral studies is permitted provided no new study drugs are added to the patient's drug regimen for 4 weeks before or after initiation of SMX/TMP.

Prior Medication:

Allowed:

• Prior aerosolized pentamidine and dapsone for primary PCP prophylaxis.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Known adverse reactions to sulfa, trimethoprim, or SMX/TMP.
• Inability to comply with dosing schedule or complete dosing record.

Concurrent Medication:

Excluded:

• Procysteine.
• Glutathione.
• N-acetylcysteine (NAC).
• Antihistamines (unless used for symptomatic treatment of study drug toxicity).
• Systemic corticosteroids (unless used for replacement purposes).
• Leucovorin calcium (unless used for symptomatic treatment of study drug toxicity).
• TMP or sulfa drugs outside of the study.

Prior Medication:

Excluded at any time:

• Prior SMX/TMP as primary PCP prophylaxis.

Excluded within 4 weeks prior to study entry:

• Initiation of antiretroviral agents.
• Initiation of anti-infective agents (including SMX/TMP for another indication).

Excluded within 2 weeks prior to study entry:

• Antihistamines.
• Procysteine.
• Glutathione.
• N-acetylcysteine (NAC).
• Systemic corticosteroids (unless used for replacement purposes).
• Leucovorin calcium.
• TMP and sulfa drugs separately.