Fluconazole Compared with Ketoconazole for the Treatment of Candida Esophagitis in AIDS: A Randomized Trial

OBJECTIVE: To determine the clinical and endoscopic response of candida esophagitis to antifungal therapy and to compare the two oral antifungal agents, fluconazole and ketoconazole. DESIGN: Multicenter, randomized, double-blind trial. SETTING: Fifteen U.S. centers including university, private practice, and county hospital settings. PATIENTS: A total of 169 patients with the acquired immunodeficiency syndrome (AIDS); odynophagia, dysphagia, or retrosternal pain; white esophageal plaques at endoscopy; and pseudohyphae on esophageal brushings or biopsies. INTERVENTION: Patients were randomly assigned to fluconazole (100 mg/d) or ketoconazole (200 mg/d). Doses were doubled at week 1 or 2 if no symptomatic improvement had occurred during the preceding week. Therapy was continued for 2 weeks after resolution of symptoms or for a maximum of 8 weeks. MEASUREMENTS: Patients were clinically evaluated weekly, and laboratory tests were done every 2 weeks. Endoscopy was repeated within 5 days after the end of therapy. RESULTS: A total of 143 patients were clinically evaluable (assessed within 7 days after therapy), and 129 patients were endoscopically evaluable (endoscopy repeated after therapy). Endoscopic cure occurred in 91% of patients treated with fluconazole and in 52% of those given ketoconazole for a difference of 39% (95% Cl, 24% to 52%; P less than 0.001). Esophageal symptoms resolved in 85% of fluconazole-treated patients and in 65% of ketoconazole-treated patients for a difference of 20% (Cl, 6% to 34%; P = 0.006). Intention-to-treat analyses also yielded statistically significant differences for the comparisons listed above. Side effects were minimal and comparable in the two groups; only one patient in each group had therapy discontinued for adverse effects that were possibly related to the study medications. CONCLUSIONS: Fluconazole is associated with significantly greater rates of endoscopic and clinical cure than ketoconazole in patients with AIDS and candida esophagitis. Both drugs appear to be safe and well tolerated.