Christine H Lee1, Theodore Steiner2, Elaine O Petrof3, Marek Smieja1, Diane Roscoe4, Anouf Nematallah2, J Scott Weese5, Stephen Collins6, Paul Moayyedi6, Mark Crowther7, Mark J Ropeleski3, Padman Jayaratne8, David Higgins9, Yingfu Li10, Neil V Rau11, Peter T Kim12. 1. 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. 2. Division of Infectious Diseases and Immunity and Infection Research Centre, Vancouver Hospital and University of British Columbia, Vancouver, British Columbia, Canada. 3. Gastrointestinal Diseases Research Unit, Department of Medicine, Queen's University, Kingston, Ontario, Canada. 4. Division of Medical Microbiology and Infection Control, Vancouver General Hospital and University of British Columbia, Vancouver, British Columbia, Canada. 5. Centre for Public Health and Zoonoses, Department of Pathobiology, University of Guelph, Guelph, Ontario, Canada. 6. Farncombe Family Digestive Health Research Institute, Division of Gastroenterology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada. 7. Department of Medicine, McMaster University, Hamilton, Ontario, Canada3St Joseph's Healthcare, Hamilton, Ontario, Canada. 8. Hamilton Regional Laboratory Medicine Program, Department of Pathology & Molecular Medicine, McMaster University, Hamilton, Ontario, Canada3St Joseph's Healthcare, Hamilton, Ontario, Canada. 9. St Joseph's Healthcare, Hamilton, Ontario, Canada. 10. Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada. 11. Division of Infectious Diseases, Department of Medicine, University of Toronto, Toronto, Ontario, Canada12Halton Healthcare Services, Oakville, Ontario, Canada. 12. 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.
Abstract
IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS: Patients were randomly allocated to receive frozen (n = 114) or fresh (n = 118) FMT via enema. MAIN OUTCOMES AND MEASURES: 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 FMTgroup 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 AND RELEVANCE: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01398969.
RCT Entities:
IMPORTANCE: Clostridium difficileinfection (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. DESIGN, SETTING, AND PARTICIPANTS: 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. INTERVENTIONS:Patients were randomly allocated to receive frozen (n = 114) or fresh (n = 118) FMT via enema. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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. TRIAL REGISTRATION: clinicaltrials.gov Identifier:NCT01398969.
Authors: Christopher Staley; Matthew J Hamilton; Byron P Vaughn; Carolyn T Graiziger; Krista M Newman; Amanda J Kabage; Michael J Sadowsky; Alexander Khoruts Journal: Am J Gastroenterol Date: 2017-02-14 Impact factor: 10.864