Marcel Wolbers.

All authors vouch for the completeness and precision of the info presented. Cipla and Ranbaxy Laboratories supplied amphotericin B and fluconazole, respectively, at a lower life expectancy cost. Flucytosine was purchased at complete price from a pharmacy. None of the drug producers or suppliers experienced any role in the study design, data analysis and accrual, or manuscript preparation. Laboratory Investigations Lumbar punctures were performed weekly for the initial month of treatment and while clinically indicated. Quantitative yeast counts were identified for all specimens.5 All strains were verified as cryptococcus species. For details, see the Supplementary Appendix, available at NEJM.org. Treatment Patients were randomly assigned to one of three induction remedies. Patients in group 1 received intravenous amphotericin B at a dosage of 1 1 mg per kilogram per day for 4 weeks, followed by oral fluconazole at a dose of 400 mg per day for 6 weeks, that was in line with local practice at the inception of the study.Prior to the second interim evaluation, we observed that the entire mortality was approximately 20 percent, which was lower than anticipated but consistent with the results of a recently available study involving similar sufferers. 14 After discussion with the safety and data monitoring board and the National Institute of General Medical Sciences, and with the group assignments still concealed, we calculated that we would have to enroll a total of 1350 patients to preserve the same power for the same total risk reduction. After spending 0.0005 alpha for the first interim analysis, and after recalculation of the sample size , the alpha level required for the sequential hypotheses was 0.0494, with no adjustment for multiple testing. We tested for between-group distinctions in the principal outcome using Fisher’s exact test.