A Randomised, Open-Label, Comparative Study of Itraconazole vs Amphotericin B for the Induction Therapy of Penicilliosis. (360G-Wellcome-096471_Z_11_Z)

Penicilliosis is emerging as one of the three most common HIV-associated opportunistic infections in Asia.Despite the rapid growing HIV epidemics in a region that houses one half of the worlds population, there hasnot been a single randomised controlled trial to evaluate the treatment of penicilliosis. The currentrecommendation of amphotericin B for 2 weeks followed by itraconazole for 10 weeks is based on onenon-comparative study [1]. Amphotericin B has extremely limited availability, has significant side effects,needs to adminstered through a vein daily over 6 hours of infusion, and is prohibitively expensive in mostareas of Asia. Itraconazole, on the other hand, is widely available in local pharmacies throughout Asia, canbe given orally at a fraction of the price. Further, data from available case series suggest that itraconazoleand amphotericin B have similar efficacies. We therefore propose to conduct a randomised, open-label,non-inferiority trial of the efficacy of itraconazole versus amphotericin B for penicilliosis. 440 adults from inand outpatient settings with culture-confirmed penicilliosis will be recruited, randomly allocated to eitheritraconazole or amphotericin B treatment, monitored daily in-hospital for 2 weeks, and at monthly intervalsfor a total of 6 months. Primary outcome is mortality at 2 weeks. Secondary outcomes include 6-monthsurvival, clinical response, relapse, drug tolerability, and economic costs. Correlates of interests includeadmission prognostic factors, time-to-culture-sterilization, fungicidal activities, pharmacokinetic parameters,and serologic titres. These results will be available within five years and will either change or support currenttreatment guidelines for penicilliosis.