Fecal transplants by pill noninferior to colonoscopy delivery
The primary outcome of the unblinded, randomized trial was the proportion of patients without recurrent Clostridium difficile infection 12 weeks after fecal transplant.
Fecal microbiota transplantation (FMT) by oral capsules may be an effective approach to treating recurrent Clostridium difficile infection, a randomized noninferiority trial concluded.
To determine whether fecal transplant by oral capsule is noninferior to delivery by colonoscopy, researchers conducted an unblinded, randomized trial in three academic centers in Alberta, Canada, between October 2014 and September 2016, with follow-up to December 2016.
The primary outcome was the proportion of patients without recurrent C. diff infection 12 weeks after fecal transplant. Secondary outcomes included serious and minor adverse events; changes in quality of life by the 36-Item Short Form Survey, which uses a scale of 0 (worst possible quality of life) to 100 (best quality of life); and 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). The trial's noninferiority margin was 15%.
Results were published by JAMA on Nov. 28. Among 116 patients, 57 were randomized to the capsule group and 59 to the colonoscopy group. One hundred five patients, 53 in the capsule group and 52 in the colonoscopy group, completed the trial. Recurrent C. diff was prevented after a single treatment in 96.2% of the capsule group (51 of 53 patients) and the colonoscopy group (50 of 52 patients) (difference, 0%; P<0.001).
Minor adverse event rates were 5.4% in the capsule group and 12.5% in the colonoscopy group. No significant between-group difference was seen in improvement in quality of life. A significantly greater proportion of participants receiving capsules versus colonoscopy rated their experience as “not at all unpleasant” (66% vs. 44%; difference, 22%; P=0.01).
The authors wrote, “Currently, most patients with [recurrent C. diff infection] are referred to gastroenterology or infectious diseases, and the method and route in which FMT is administered are specialty dependent. Although colonoscopy delivery is more invasive, resource intensive, costly, and inconvenient for patients, it has the advantage of identifying alternative diagnoses. Conversely, when FMT is given by oral capsules, it can be administered in an office setting, which could substantially reduce cost and wait time. Complete economic evaluations are needed to understand the value and efficiency of FMT by oral capsule.”
An editorial emphasized the importance of further research about the optimal timing and format of fecal transplantation, as well as the role for rational design of defined microbial consortia.
“While it is encouraging that capsules appear to be a viable delivery route for FMT, a number of additional approaches still deserve consideration in future research,” the editorial stated. “These include vancomycin tapers with and without ‘chasers' of fidaxomicin/rifaximin, defined microbial communities, and sterile fecal-derived products. If these latter approaches prove to be effective, they may supplant standard FMT and other undefined microbial consortia, making even convenient, capsule-based FMT a tough pill to swallow.”