Effect of oral capsule– vs colonoscopy-delivered fecal microbiota transplantation on recurrent Clostridium difficile infection

A randomized clinical trial

Dina Kao, Brandi Roach, Marisela Silva, Paul Beck, Kevin Rioux, Gilaad G. Kaplan, Hsiu Ju Chang, Stephanie Coward, Karen J. Goodman, Huiping Xu, Karen Madsen, Andrew Mason, Gane Ka Shu Wong, Juan Jovel, Jordan Patterson, Thomas Louie

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

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; P < .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%]; P = .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.

Original languageEnglish (US)
Pages (from-to)1985-1993
Number of pages9
JournalJAMA - Journal of the American Medical Association
Volume318
Issue number20
DOIs
StatePublished - Nov 28 2017

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Clostridium Infections
Clostridium difficile
Colonoscopy
Capsules
Randomized Controlled Trials
Quality of Life
Alberta
Fecal Microbiota Transplantation
Canada

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effect of oral capsule– vs colonoscopy-delivered fecal microbiota transplantation on recurrent Clostridium difficile infection : A randomized clinical trial. / Kao, Dina; Roach, Brandi; Silva, Marisela; Beck, Paul; Rioux, Kevin; Kaplan, Gilaad G.; Chang, Hsiu Ju; Coward, Stephanie; Goodman, Karen J.; Xu, Huiping; Madsen, Karen; Mason, Andrew; Wong, Gane Ka Shu; Jovel, Juan; Patterson, Jordan; Louie, Thomas.

In: JAMA - Journal of the American Medical Association, Vol. 318, No. 20, 28.11.2017, p. 1985-1993.

Research output: Contribution to journalArticle

Kao, D, Roach, B, Silva, M, Beck, P, Rioux, K, Kaplan, GG, Chang, HJ, Coward, S, Goodman, KJ, Xu, H, Madsen, K, Mason, A, Wong, GKS, Jovel, J, Patterson, J & Louie, T 2017, 'Effect of oral capsule– vs colonoscopy-delivered fecal microbiota transplantation on recurrent Clostridium difficile infection: A randomized clinical trial', JAMA - Journal of the American Medical Association, vol. 318, no. 20, pp. 1985-1993. https://doi.org/10.1001/jama.2017.17077
Kao, Dina ; Roach, Brandi ; Silva, Marisela ; Beck, Paul ; Rioux, Kevin ; Kaplan, Gilaad G. ; Chang, Hsiu Ju ; Coward, Stephanie ; Goodman, Karen J. ; Xu, Huiping ; Madsen, Karen ; Mason, Andrew ; Wong, Gane Ka Shu ; Jovel, Juan ; Patterson, Jordan ; Louie, Thomas. / Effect of oral capsule– vs colonoscopy-delivered fecal microbiota transplantation on recurrent Clostridium difficile infection : A randomized clinical trial. In: JAMA - Journal of the American Medical Association. 2017 ; Vol. 318, No. 20. pp. 1985-1993.
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AU - Beck, Paul

AU - Rioux, Kevin

AU - Kaplan, Gilaad G.

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AU - Coward, Stephanie

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AU - Madsen, Karen

AU - Mason, Andrew

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N2 - 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; P < .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%]; P = .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.

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