1955. A Randomized, Double-Blind Study to Evaluate the Safety, Tolerability, and Efficacy of Caspofungin Versus Amphotericin B Deoxycholate in the Treatment of Invasive Candidiasis in Neonates and Infants ≤3 Months of Age
Session: Poster Abstract Session: Clinical Trials
Saturday, October 6, 2018
Room: S Poster Hall
Background: Candida species are the most common fungal pathogens in infants aged <1 year. Current antifungal regimens such as amphotericin B deoxycholate (dAmB) are associated with serious toxicity and multiple drug-drug interactions. The echinocandin caspofungin has less toxicity than dAmB and is approved for candidemia and other invasive Candida infections (ICI) in pediatric populations aged ≥3 months to 17 years. We investigated the efficacy of caspofungin in patients (pts) aged ≤3 months in ICI.

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.

Jason Kim, MD, MSCE1, Firdose Lambey Nakwa, MBBCh, FCPaeds, MMed Paeds2, Fábio De Araujo Motta, MD, PhD3, Perla Salcedo Lozada, MD4, Derya Alabaz, MD5, Hong Liu, MS1, Keisha Bloise, MS1, Mary Beth Dorr, PhD1, Leah J. Anderson Gaffney, PhD1 and Nicholas Kartsonis, MD1, (1)Merck & Co., Inc., Kenilworth, NJ, (2)Chris Hani Baragwanath Academic Hospital, University of Witwatersrand, Johannesburg, South Africa, (3)Hospital Pequeno Príncipe, Curitiba, Paraná, Brazil, (4)General Hospital of Ecatepec Las Américas, Instituto de Salud del Estado de México, Mexico City, Mexico, (5)Cukurova University, Adana, Turkey


J. Kim, Merck & Co., Inc.: Employee , Salary .

F. Lambey Nakwa, Merck & Co., Inc.: Principal Investigator , Research support .

F. De Araujo Motta, Merck & Co., Inc.: Grant Investigator , Grant recipient .

P. Salcedo Lozada, Merck & Co., Inc.: Investigator , Research support .

D. Alabaz, Merck & Co., Inc.: Investigator , Research support .

H. Liu, Merck & Co., Inc.: Employee , Salary .

K. Bloise, Merck & Co., Inc.: Employee , Salary .

M. B. Dorr, Merck & Co., Inc.: Employee and Shareholder , Salary .

L. J. Anderson Gaffney, Merck & Co., Inc.: Employee , Salary .

N. Kartsonis, Merck & Co., Inc.: Employee and Shareholder , Salary .

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