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Clin Infect Dis. 2019 Jan 7;68(2):196-203. doi: 10.1093/cid/ciy484.

A Randomized, Placebo-controlled Trial of Fidaxomicin for Prophylaxis of Clostridium difficile-associated Diarrhea in Adults Undergoing Hematopoietic Stem Cell Transplantation.

Author information

1
Department of Medicine, University of Chicago, Illinois.
2
UCLA Medical Center, Los Angeles, California.
3
Emory University School of Medicine, Atlanta, Georgia.
4
University of Miami Miller School of Medicine, Florida.
5
Loyola University Stritch School of Medicine, Maywood, Illinois.
6
Indiana Blood and Marrow Transplantation, Indianapolis.
7
Blood and Marrow Transplant Group, Atlanta, Georgia.
8
Division of Infectious Diseases, University of Michigan, Ann Arbor.
9
Department of Infectious Diseases, Infection Control, and Employee Health, University of Texas MD Anderson Cancer Center, Houston.
10
Division of Vaccine and Infectious Disease, Fred Hutchinson Cancer Research Center, University of Washington, Seattle.
11
Duke University, Durham, North Carolina.
12
Washington University School of Medicine, St Louis, Missouri.
13
Merck & Co., Inc., Kenilworth, New Jersey.
14
Tufts University School of Medicine, Boston, Massachusetts.

Erratum in

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 (200 mg) or a 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 = .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 = .0014). Drug-related adverse events occurred in 15.0% of fidaxomicin recipients and 20.0% of placebo recipients.

Conclusions:

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.

Clinical Trials Registration:

NCT01691248.

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