A Randomized, Placebo-Controlled Trial of Fidaxomicin for Prophylaxis of Clostridium difficile Associated Diarrhea in Adults undergoing Hematopoietic Stem Cell Transplantation. Journal Article

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Authors: Mullane, KM; Winston, DJ; Nooka, A; Morris, MI; Stiff, P; Dugan, MJ; Holland, H; Gregg, K; Adachi, JA; Pergam, SA; Alexander, BD; Dubberke, ER; Broyde, N; Gorbach, SL; Sears, PS
Article Title: A Randomized, Placebo-Controlled Trial of Fidaxomicin for Prophylaxis of Clostridium difficile Associated Diarrhea in Adults undergoing Hematopoietic Stem Cell Transplantation.
Abstract: Background: Clostridium difficile-associated diarrhea (CDAD) is common during hematopoietic stem-cell transplantation (HSCT) and is associated with increased morbidity and mortality. We evaluated fidaxomicin for prevention of CDAD in HSCT patients. Methods: In this double-blind study, subjects undergoing HSCT with fluoroquinolone prophylaxis stratified by transplant type (autologous/allogeneic) were randomized to once-daily oral fidaxomicin 200mg or matching placebo. Dosing began within 2 days of starting conditioning or fluoroquinolone prophylaxis and continued until 7 days after neutrophil engraftment or completion of fluoroquinolone prophylaxis/clinically indicated antimicrobials for up to 40 days. The primary endpoint was CDAD incidence through 30 days after study medication. The primary endpoint analysis counted confirmed CDAD, receipt of CDAD-effective medications (for any indication), and missing CDAD assessment (for any reason, including death) as failures; this composite analysis is referred to as "prophylaxis failure" to distinguish from the pre-specified sensitivity analysis, which counted only confirmed CDAD (by toxin immunoassay or nucleic acid amplification test) as failure. Results: Of 611 subjects enrolled, 600 were treated and analyzed. Prophylaxis failure was similar in fidaxomicin and placebo recipients (28.6% vs 30.8%; difference 2.2% [-5.1, 9.5], p=0.278). However, most failures were due to non-CDAD events. Confirmed CDAD was lower in fidaxomicin vs placebo recipients (4.3% vs 10.7%; difference 6.4% [2.2, 10.6], p=0.0014). Drug-related adverse events occurred in 15.0% of fidaxomicin recipients and 20.0% of placebo recipients. Conclusion: While no difference was demonstrated between arms in the primary analysis, results of the sensitivity analysis demonstrated that fidaxomicin significantly reduced the incidence of CDAD in HSCT recipients. ClinicalTrials.gov: NCT01691248.
Journal Title: Clinical Infectious Diseases
ISSN: 1058-4838
Publisher: Unknown  
Date Published: 2018