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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pneumonia, Pneumocystis Carinii, HIV Infections

Intervention / Treatment
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* Drug: Sulfamethoxazole-Trimethoprim


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 13 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Sulfamethoxazole-Trimethoprim|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Trimethoprim-Sulfamethoxazole Combination, Pneumonia, Pneumocystis carinii, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Sulfamethoxazole-Trimethoprim