title: Frozen vs Fresh Fecal Microbiota Transplantation and Clinical Resolution of Diarrhea in Patients With Recurrent Clostridium difficile Infection: A Randomized Clinical Trial.
abstract: OBJECTIVE
  Clostridium difficile infection (CDI) is a major burden in health care and community settings. CDI recurrence is of particular concern because of limited treatment options and associated clinical and infection control issues. Fecal microbiota transplantation (FMT) is a promising, but not readily available, intervention.
  
  
  OBJECTIVE
  To determine whether frozen-and-thawed (frozen, experimental) FMT is noninferior to fresh (standard) FMT in terms of clinical efficacy among patients with recurrent or refractory CDI and to assess the safety of both types of FMT.
  
  
  METHODS
  Randomized, double-blind, noninferiority trial enrolling 232 adults with recurrent or refractory CDI, conducted between July 2012 and September 2014 at 6 academic medical centers in Canada.
  
  
  METHODS
  Patients were randomly allocated to receive frozen (n = 114) or fresh (n = 118) FMT via enema.
  
  
  METHODS
  The primary outcome measures were clinical resolution of diarrhea without relapse at 13 weeks and adverse events. Noninferiority margin was set at 15%.
  
  
  RESULTS
  A total of 219 patients (n = 108 in the frozen FMT group and n = 111 in the fresh FMT group) were included in the modified intention-to-treat (mITT) population and 178 (frozen FMT: n = 91, fresh FMT: n = 87) in the per-protocol population. In the per-protocol population, the proportion of patients with clinical resolution was 83.5% for the frozen FMT group and 85.1% for the fresh FMT group (difference, -1.6% [95% CI, -10.5% to ∞]; P = .01 for noninferiority). In the mITT population the clinical resolution was 75.0% for the frozen FMT group and 70.3% for the fresh FMT group (difference, 4.7% [95% CI, -5.2% to ∞]; P < .001 for noninferiority). There were no differences in the proportion of adverse or serious adverse events between the treatment groups.
  
  
  CONCLUSIONS
  Among adults with recurrent or refractory CDI, the use of frozen compared with fresh FMT did not result in worse proportion of clinical resolution of diarrhea. Given the potential advantages of providing frozen FMT, its use is a reasonable option in this setting.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier:NCT01398969.
authors.affiliation: Hamilton Regional Laboratory Medicine Program, Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada2Department of Medicine, McMaster University, Hamilton, Ontario, Canada3St Joseph's Healthcare, Hamilton, Ontario, C.
authors.forename: Christine H
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Division of Infectious Diseases and Immunity and Infection Research Centre, Vancouver Hospital and University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Theodore
authors.initials: T
authors.lastname: Steiner
authors.affiliation: Gastrointestinal Diseases Research Unit, Department of Medicine, Queen's University, Kingston, Ontario, Canada.
authors.forename: Elaine O
authors.initials: EO
authors.lastname: Petrof
authors.affiliation: Hamilton Regional Laboratory Medicine Program, Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada2Department of Medicine, McMaster University, Hamilton, Ontario, Canada3St Joseph's Healthcare, Hamilton, Ontario, C.
authors.forename: Marek
authors.initials: M
authors.lastname: Smieja
authors.affiliation: Division of Medical Microbiology and Infection Control, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Diane
authors.initials: D
authors.lastname: Roscoe
authors.affiliation: Division of Infectious Diseases and Immunity and Infection Research Centre, Vancouver Hospital and University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Anouf
authors.initials: A
authors.lastname: Nematallah
authors.affiliation: Centre for Public Health and Zoonoses, Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada.
authors.forename: J Scott
authors.initials: JS
authors.lastname: Weese
authors.affiliation: Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Stephen
authors.initials: S
authors.lastname: Collins
authors.affiliation: Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Moayyedi
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada3St Joseph's Healthcare, Hamilton, Ontario, Canada.
authors.forename: Mark
authors.initials: M
authors.lastname: Crowther
authors.affiliation: Gastrointestinal Diseases Research Unit, Department of Medicine, Queen's University, Kingston, Ontario, Canada.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Ropeleski
authors.affiliation: Hamilton Regional Laboratory Medicine Program, Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada3St Joseph's Healthcare, Hamilton, Ontario, Canada.
authors.forename: Padman
authors.initials: P
authors.lastname: Jayaratne
authors.affiliation: St Joseph's Healthcare, Hamilton, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Higgins
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Yingfu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Ontario, Canada12Halton Healthcare Services, Oakville, Ontario, Canada.
authors.forename: Neil V
authors.initials: NV
authors.lastname: Rau
authors.affiliation: Hamilton Regional Laboratory Medicine Program, Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada10Department of Mathematics and Statistics, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Kim
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016360:Clostridioides difficile; D015925:Cryopreservation; D003967:Diarrhea / Q000209:etiology / Q000628:therapy*; D004311:Double-Blind Method; D004761:Enterocolitis, Pseudomembranous / Q000150:complications / Q000628:therapy*; D000069467:Fecal Microbiota Transplantation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016896:Treatment Outcome