Table 2.
Early Fungicidal Activity Comparison of Oral Lipid Nanocrystal Amphotericin vs Intravenous Amphotericin Controls
| CSF Clearance and Sterility Characteristic | Oral LNC Amphotericin B With 2 IV Loading Doses, Cohort 2 |
All-Oral LNC Amphotericin B, Cohort 4 |
IV Amphotericin B, Controls Cohorts 1–4 |
|---|---|---|---|
| Number randomized | 40 | 40 | 41 |
| Number contributing to EFA and sterility analyses | 37 | 33 | 34 |
| EFA by general linear modelsa | |||
| Maximum | 2.352 | 4.161 | 1.234 |
| 75th percentile | 0.518 | 0.379 | 0.645 |
| Median | 0.324 | 0.249 | 0.366 |
| 25th percentile | 0.216 | 0.195 | 0.260 |
| Minimum | 0.000 | 0.017 | 0.066 |
| EFA mean (95% CI) | 0.423 (.294 to .551) |
0.402 (.165 to .640) |
0.455 (.359 to .551) |
| EFA difference, mean (95% CI) | −0.032 (−.196 to .131) |
−0.053 (−.317 to .211) |
Reference |
| EFA mean (95% CI) outliers imputedb | 0.423 (.294 to .551) |
0.348 (.211 to .484) |
0.455 (.359 to .551) |
| EFA by mixed model slope (95% CI)a | 0.328 (.270 to .386) |
0.253 (.193 to .312) |
0.374 (.310 to .438) |
| CSF sterile at 2 wk, N (%) | 23 (62.2%) | 21 (63.6%) | 23 (67.6%) |
| CSF sterile ever, N (%) | 36 (97.3%) | 30 (90.9%) | 28 (82.4%) |
| Additional IV amphotericin B received during induction therapy | 1 | 0 | 0 |
| CSF culture positive at >28 dc | 4 (10%) | 5 (12.5%) | 2 (4.9%) |
| CSF culture positive >28 d or death | 7 (17.5%) | 11 (27.5%) | 8 (19.5%) |
Participants contributing data had nonsterile CSF at baseline and at least 2 lumbar punctures during study days 1–18. EFA unit is in log10 Cryptococcus colony-forming units (CFU) per milliliter CSF per day. Supplementary Table 2 provides data for cohorts 1 and 3. Supplementary Figure 1 provides individual participant-level EFA plot, and Supplementary Figure 2 provides summary mean EFA (95% CI) by cohort and for historical oral regimens.
Abbreviations: CI, confidence interval; CSF, cerebrospinal fluid; EFA, early fungicidal activity; IV, intravenous; LNC, lipid nanocrystal.
aMixed regression model: log10 CSF ∼ arm + day + arm * day, with random intercepts and random slopes for day with patients as the random effect.
bEFA of participant 110 807 (cohort 4) has EFA = 4.161 log10 CFU/mL/d is imputed as 2.352 (cohort second highest EFA) as a sensitivity analysis.
c Supplementary Table 4 provides quantitative culture data for all positive CSF cultures beyond day 28.