A Double-Blind, Randomized, Placebo-Controlled Trial of Itraconazole Capsules as Antifungal Prophylaxis for Neutropenic Patients

Abstract

To evaluate the efficacy of itraconazole capsules in prophylaxis for fungal infections in neutropenic patients, we conducted a prospective, double-blind, placebo-controlled, randomized trial. Patients with hematologic malignancies or those who received autologous bone marrow transplants were assigned either a regimen of itraconazole (100 mg orally twice daily; n=104) or of placebo (n=106). Overall, fungal infections (superficial or systemic) occurred more frequently in the placebo group (15% vs. 6%; P=.03). There were no differences in the empirical use of amphotericin B or systemic fungal infections. Among patients with neutropenia that was profound (<100 neutrophils/mm3) and prolonged (for at least 7 days), those receiving itraconazole used less empirical amphotericin B (22% vs. 61%; P=.0001) and developed fewer systemic fungal infections (6% vs. 19%; P=.04). For patients with profound and prolonged neutropenia, itraconazole capsules at the dosage of 100 mg every 12 h reduce the frequency of systemic fungal infections and the use of empirical amphotericin B.

Network Meta-analysis and Pharmacoeconomic Evaluation of Fluconazole, Itraconazole, Posaconazole, and Voriconazole in Invasive Fungal Infection Prophylaxis

“…We analyzed 19 and 14 studies that reported overall mortality rates at 100 days (12,(20)(21)(22)(23)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38) (Fig. 4c).…”

Engraftment syndrome following autologous hematopoietic stem cell transplantation: definition of diagnostic criteria

“…All patients received acyclovir for prophylaxis of herpes simplex, and only the first 28 patients received antibacterial prophylaxis (ciprofloxacin). Until July 1997, antifungal prophylaxis was given according to a randomized trial that compared itraconazol and placebo, 9 and after that, all patients received fluconazole. The patients were admitted to single rooms without HEPA filters or laminar airflow.…”

A prospective randomized trial of itraconazole vs fluconazole for the prevention of fungal infections in patients with acute leukemia and hematopoietic stem cell transplant recipients

“…The first studies, using itraconazole capsules, failed to show efficacy in anti-Aspergillus prophylaxis. 20,21,28,29 When oral solution itraconazole was introduced, some studies reported reduction in the incidence of IA with itraconazole prophylaxis compared to historical controls, placebo or polyenes. 19,27,29 There are three randomized prospective studies comparing itraconazole with fluconazole as antifungal prophylaxis.…”

“…17 Recently, two new itraconazole formulations, an oral hydroxypropyl-b-cyclodextrin solution, and an intravenous formulation, have become available and provide favorable pharmacological profiles and good anti-Candida as well as anti-Aspergillus activity. 18 Studies to support the superiority of itraconazole over placebo in preventing IFIs are already available [19][20][21] and three recent studies comparing itraconazole with fluconazole as prophylaxis have shown equivalence, or a slight superiority for itraconazole. [22][23][24] We performed a randomized trial comparing oral and intravenous itraconazole with oral and intravenous fluconazole, administered to HSCT recipients and patients with acute leukemia (AL), to determine whether itraconazole is superior to fluconazole in the prevention of IFIs, particularly invasive aspergillosis (IA).…”