1. JAMA. 2017 Nov 28;318(20):1985-1993. doi: 10.1001/jama.2017.17077.

Effect of Oral Capsule- vs Colonoscopy-Delivered Fecal Microbiota Transplantation
on Recurrent Clostridium difficile Infection: A Randomized Clinical Trial.

Kao D(1), Roach B(1), Silva M(2), Beck P(3), Rioux K(4), Kaplan GG(3), Chang
HJ(5), Coward S(6), Goodman KJ(1), Xu H(7), Madsen K(1), Mason A(1), Wong
GK(8)(9)(10), Jovel J(8), Patterson J(8), Louie T(2).

Author information: 
(1)Division of Gastroenterology, Department of Medicine, University of Alberta,
Edmonton, Alberta, Canada.
(2)Division of Infectious Diseases, Department of Medicine, University of
Calgary, Calgary, Alberta, Canada.
(3)Division of Gastroenterology, Department of Medicine, University of Calgary,
Calgary, Alberta, Canada.
(4)Division of Gastroenterology, Department of Medicine, University of Victoria, 
Victoria, British Columbia, Canada.
(5)University of Alberta, Edmonton, Alberta, Canada.
(6)Department of Community Health Sciences, University of Calgary, Calgary,
Alberta, Canada.
(7)Department of Biostatistics, Indiana University, Indianapolis.
(8)Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
(9)Department of Biological Sciences, University of Alberta, Edmonton, Alberta,
Canada.
(10)BGI-Shenzhen, Shenzhen, China.

Comment in
    JAMA. 2017 Nov 28;318(20):1979-1980.
    J Thorac Dis. 2018 Apr;10(Suppl 9):S1081-S1083.

Importance: Fecal microbiota transplantation (FMT) is effective in preventing
recurrent Clostridium difficile infection (RCDI). However, it is not known
whether clinical efficacy differs by route of delivery.
Objective: To determine whether FMT by oral capsule is noninferior to colonoscopy
delivery in efficacy.
Design, Setting, and Participants: Noninferiority, unblinded, randomized trial
conducted in 3 academic centers in Alberta, Canada. A total of 116 adult patients
with RCDI were enrolled between October 2014 and September 2016, with follow-up
to December 2016. The noninferiority margin was 15%.
Interventions: Participants were randomly assigned to FMT by capsule or by
colonoscopy at a 1:1 ratio.
Main Outcomes and Measures: The primary outcome was the proportion of patients
without RCDI 12 weeks after FMT. Secondary outcomes included (1) serious and
minor adverse events, (2) changes in quality of life by the 36-Item Short Form
Survey on a scale of 0 (worst possible quality of life) to 100 (best quality of
life), and (3) patient perception on a scale of 1 (not at all unpleasant) to 10
(extremely unpleasant) and satisfaction on a scale of 1 (best) to 10 (worst).
Results: Among 116 patients randomized (mean [SD] age, 58 [19] years; 79 women
[68%]), 105 (91%) completed the trial, with 57 patients randomized to the capsule
group and 59 to the colonoscopy group. In per-protocol analysis, prevention of
RCDI after a single treatment was achieved in 96.2% in both the capsule group
(51/53) and the colonoscopy group (50/52) (difference, 0%; 1-sided 95% CI, -6.1% 
to infinity; Pā€‰<ā€‰.001), meeting the criterion for noninferiority. One patient in 
each group died of underlying cardiopulmonary illness unrelated to FMT. Rates of 
minor adverse events were 5.4% for the capsule group vs 12.5% for the colonoscopy
group. There was no significant between-group difference in improvement in
quality of life. A significantly greater proportion of participants receiving
capsules rated their experience as "not at all unpleasant" (66% vs 44%;
difference, 22% [95% CI, 3%-40%]; Pā€‰=ā€‰.01).
Conclusions and Relevance: Among adults with RCDI, FMT via oral capsules was not 
inferior to delivery by colonoscopy for preventing recurrent infection over 12
weeks. Treatment with oral capsules may be an effective approach to treating
RCDI.
Trial Registration: clinicaltrials.gov Identifier: NCT02254811.

DOI: 10.1001/jama.2017.17077 
PMCID: PMC5820695
PMID: 29183074  [Indexed for MEDLINE]