Table 2. Primary and Key Secondary Outcomes.*.
| Outcome | Group 1, Amphotericin B (N=99) | Group 2, Amphotericin B and Flucytosine (N=100) | Group 3, Amphotericin B and Fluconazole (N=99) | Hazard Ratio or Difference in Estimated Change (95% CI)† | |||||
|---|---|---|---|---|---|---|---|---|---|
| Group 2 vs. Group 1 | P Value | Group 3 vs. Group 1 | P Value | Group2 vs. Group 3 | P Value | ||||
| Coprimary outcomes | |||||||||
| Death by day 14 | 0.57 (0.30 to 1.08) | 0.08 | 0.78 (0.44 to 1.41) | 0.42 | 0.72 (0.3 to 1.41) | 0.34 | |||
| No. of deaths | 25 | 15 | 20 | ||||||
| Probability of survival (95% CI) | 0.75 (0.67 to 0.84) | 0.85 (0.78 to 0.92) | 0.80 (0.73 to 0.88) | ||||||
| Death by day 70‡ | 0.61 (0.39 to 0.97) | 0.04 | 0.71 (0.45to 1.11) | 0.13 | 0.87 (0.53 to 1.42) | 0.57 | |||
| No. of deaths | 44 | 30 | 33 | ||||||
| Probability of survival (95% CI) | 0.56 (0.47 to 0.66) | 0.69 (0.61 to 0.79) | 0.67 (0.58 to 0.77) | ||||||
| Secondary outcomes | |||||||||
| Death by day 70 in the per-protocol population | 0.60 (036 to 0.99) | 0.04 | 0.68 (0.41.to 1.11) | 0.12 | 0.88 (0.521 to 1.51) | 0.65 | |||
| No. of deaths/no. of patients included in analysis | 37/87 | 26/92 | 27/88 | ||||||
| Probability of survival (95% CI) | 0.58 (0.48 to 0.69) | 0.71 (0.63 to 0.81) | 0.69 (0.60 to 0.80) | ||||||
| Death by day 182§ | 0.56 (0.36 to 0.86) | 0.01 | 0.78 (0.53 to 1.16) | 0.23 | 0.72 (0.461 to 1.12) | 0.14 | |||
| No. of deaths | 53 | 34 | 45 | ||||||
| Probability of survival (95% CI) | 0.46 (0.37 to 0.57) | 0.65 (0.56 to 0.75) | 0.54 (0.45 to 0.65) | ||||||
| Estimated change in CSF fungal count in first 14 days (95% CI)—log10CFU/ml/day | −0.31 (−0.34 to −0.29) | −0.42 (−0.44 to −0.40) | −0.32 (−0.34 to −0.29) | −0.10(−0.14 to −0.07) | <0.001 | 0.00 (−0.04 to 0.03) | 0.83 | −0.10 (−0.14 to −0.07) | <0.001 |
| CSF fungal clearance | 3.18 (2.17 to 4.66) | <0.001 | 1.39 (0.94to 2.07) | 0.10 | 2.29 (1.591 to 3.29) | <0:001 | |||
| No. of patients with documented clearance | 52 | 74 | 63 | ||||||
| Clearance rate per person-wk of follow-up (95% CI) | 0.17 (0.13 to 0.23) | 0.39 (0.31 to 0.50) | 0.26 (0.20 to 0.34) | ||||||
Reported results are for the intention-to-treat population unless otherwise specified and were not adjusted for baseline covariates or multiple comparisons, except for time to CSF fungal clearance, which was adjusted for baseline fungal count. In the coprimary comparisons for death by 14 days and death by 70 days in group 2 versus group 1 and in group 3 versus group 1, conservative Bonferroni multiplicity adjustment would require doubling of the P values (adjustment for multiple primary end points) or would require the P value to be four times as large (adjustment for multiple primary end points and for multiple comparisons of the combination therapies versus a common control group). For disability outcomes, see Table S2 in the Supplementary Appendix.
Hazard ratios are shown for all outcomes except for the estimated change in CSF fungal count, for which the between-group difference in the estimated change is shown.
When hazard ratios tor death by day 70 were adjusted tor baseline covariates, the results were as follows: for group 2 versus group 1, the hazard ratio was 0.62 (95% CI, 0.38 to 0.996), P=0.048; for group 3 versus group 1, the hazard ratio was 0.94 (95% CI, 0.58 to 1.51), P=0.80; and for group 2 versus group 3, the hazard ratio was 0.66 (95% CI, 0.39 to 1.10), P=0.11.
When hazard ratios for death by day 182 were adjusted for baseline covariates, the results were as follows: for group 2 versus group 1, the hazard ratio was 0.56 (95% CI, 0.36 to 0.87), P=0.01; for group 3 versus group 1, the hazard ratio was 1.01 (95% CI, 0.66 to 1.53), P=0.97; and for group 2 versus group 3, the hazard ratio was 0.55 (95% CI, 0.35 to 0.88), P=0.01.