1955. A Randomized, Double-Blind Study to Evaluate the Safety, Tolerability, and Efficacy of Caspofungin vs. Amphotericin B Deoxycholate in the Treatment of Invasive Candidiasis in Neonates and Infants ≤3 Months of Age. (26th November 2018)

• Record Type: Journal Article
• Authors: Kim, Jason; Nakwa, Firdose Lambey; Motta, Fábio De Araujo; Lozada, Perla Salcedo; Alabaz, Derya; Liu, Hong; Bloise, Keisha; Dorr, Mary Beth; Gaffney, Leah J Anderson; Kartsonis, Nicholas
• Is Part Of: Open forum infectious diseases. Volume 5(2018)Supplement 1
• Page Start: S565
• Page End: S565
• Publication Date: 2018-11-26
• Subjects: Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofy210.1611
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract: 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 aged ≤3 months in ICI. Methods: This phase 2, multicenter, randomized, double-blind, comparator-controlled study (Protocol MK0991-064; NCT01945281) enrolled patients aged ≤3 months with culture-confirmed ICI ≤96 hours before study entry. Patients 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 patients. Results: Fifty-one patients 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 (510–4, 175 g); median baseline weight (min–max) = 1, 860 g (425–6, 540 g); median gestational age (min–max) = 30.4 weeks (26–41 weeks). C. albicans was the most common species isolated. Forty-nine patients received treatment (caspofungin, N = 33; dAmB, N = 16); two additional patients did not have confirmed infections at study entry. Overall, 47 patients 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 patients 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. Two patients 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 patients 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. Patients who received caspofungin experienced fewer AEs and SAEs. Disclosures: 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.