John Bartlett, MD


July 23, 2003

In This Article

Itraconazole to Prevent Fungal Infections in Chronic Granulomatous Disease (CGD)

Gallin JI, Alling DW, Malech HL, et al. Itraconazole to prevent fungal infections in chronic granulomatous disease. N Engl J Med. 2003;348:2416-2422. Abstract These authors performed a randomized, double-blind, placebo-controlled trial of 39 patients with CGD using itraconazole at a dose of 200 mg/day for persons over 13 years of age or weighing at least 50 kg. Each participant alternated between itraconazole and placebo annually. The primary end point was severe fungal infection. The results showed 1 infection in a noncompliant patient when assigned itraconazole compared to 7 with severe fungal infections when receiving placebo. The authors conclude that itraconazole prophylaxis is effective and well tolerated in CGD.

Comment: CGD is a rare inherited disorder of phagocytic cells in which killing of microbes is impaired due to defective H2O2 to production. The consequence is that catalase-positive bacteria and fungi cause serious infections, with an average frequency of 1 per year resulting in mortality at 2% to 5% per year. Prior studies show antibiotic prophylaxis with trimethoprim/sulfamethoxazole (TMP-SMX), and interferon gamma effectively reduced bacterial infections. Nevertheless, fungal infections remained problematic with an incidence of approximately 1 per decade. The above study addresses that issue. The study design is of particular interest since it concerns the difficult challenge of a controlled trial in a rare disease. The issue is reviewed in the editorial comment by SW Lagakos,[47] who noted the novel study design, which required 10 years to enroll 39 patients. The study design was drug vs placebo alternating on an annual basis, a design that was far more acceptable to participants.


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