Pneumonia, Pneumocystis Carinii, HIV Infections
Conditions
Keywords
Trimethoprim-Sulfamethoxazole Combination, Pneumonia, Pneumocystis carinii, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Sulfamethoxazole-Trimethoprim
Brief summary
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
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.
Interventions
Sponsors
Glaxo Wellcome
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
Healthy volunteers
No
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.
Countries
Puerto Rico, Tanzania, United States
Outcome results
None listed