Methods: This phase 2, multicenter, randomized, double-blind, comparator-controlled study (Protocol MK0991-064; NCT01945281) enrolled pts aged ≤3 months with culture-confirmed ICI ≤96 hours before study entry. Pts were randomized 2:1 to IV caspofungin 2 mg/kg once daily or IV dAmB 1 mg/kg once daily. Primary endpoint was fungal-free survival (FFS) at 2 weeks post-therapy. Initial target sample size was 90 pts.
Results: 51 pts were enrolled. The study was terminated early due to low enrollment after >3.5 years’ recruitment. Median age (min-max) at enrollment = 22 days (7-88 days); male = 53.2%; median birth weight (min-max) = 1445 g (510-4175 g); median baseline weight (min-max) = 1860 g (425-6540 g); median gestational age (min-max) = 30.4 weeks (26-41 weeks). C. albicans was the most common species isolated. 49 pts received treatment (caspofungin, N = 33; dAmB, N = 16); 2 additional pts did not have confirmed infections at study entry. Overall, 47 pts were included in the full analysis set population (caspofungin, N = 31; dAmB, N = 16). FFS at 2 weeks post-therapy was 71.0% (22/31) in the caspofungin arm and 68.8% (11/16) in the dAmB arm (difference, –0.9% [95% CI, –24.3%, 27.7%]). 84.8% (28/33) of pts in the caspofungin arm and 100% (16/16) in the dAmB arm had ≥1 adverse event (AE); anemia (10/33 and 8/16, respectively) and sepsis (3/33 and 5/16, respectively) were the most common. 2 pts in each arm had investigator-assessed treatment-related AEs. Serious AEs (SAEs) were 21.2% (7/33) in the caspofungin arm and 56.3% (9/16) in the dAmB arm; 5 pts died, 2 (6%) in caspofungin arm and 3 (19%) in dAmB arm. All SAEs and deaths were unrelated to study drug.
Conclusion: Among neonates and infants with confirmed ICI, FFS at 2 weeks was similar in the caspofungin and dAmB treatment arms. Pts who received caspofungin experienced fewer AEs and SAEs.
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