Canadian researchers report that delivering fecal transplants by capsule may be as effective a method as colonoscopy delivery for treating patients with recurrent Clostridium difficile infection (RCDI), according to a study today in the Journal of the American Medical Association (JAMA).
In a randomized clinical trial conducted in three academic medical centers in Alberta, Canada, the researchers found that fecal microbiota transplantation (FMT) via oral capsule was not inferior to FMT by colonoscopy, produced similar improvements in quality of life, and resulted in fewer adverse events. In addition, fewer patients who received FMT via oral capsule characterized the experience as unpleasant.
C difficile, a common bacterium in hospital environments, is a leading cause of diarrhea in hospital patients and one of the most common healthcare-associated infections. Older patients taking antibiotics for other conditions are among the most susceptible. It can also be difficult to completely cure. As a result, recurrent infections have become a growing challenge. At least 20% of patients who get an initial CDI have a recurrent infection within 8 weeks, with the risk of RCDI being as high as 50% to 60% after three or more infections.
While antibiotic therapy remains the standard treatment for CDI and RCDI, antibiotics can contribute to relapse by wiping out the beneficial bacteria in the gut microbiome that help keep C difficile in check. FMT, in which a stool sample from a healthy donor is transplanted to the gastrointestinal tract of an infected patient to re-introduce healthy bacteria into the gut, is a non-antibiotic therapy that's shown promise in clinical studies.
But the most successful method of delivery to date has been colonoscopy. This study suggests there could be a less invasive, more tolerable option.
A viable FMT delivery route
In the noninferiority trial, 116 patients were enrolled over a 2-year period (October 2014 to September 2016) and randomized evenly to receive FMT by capsule or colonoscopy. Stool was provided by seven healthy donors. The primary outcome of the study was the proportion of patients without RCDI 12 weeks after FMT. Secondary outcomes included severe and minor adverse events, changes in quality of life, and patient perception and satisfaction. The noninferiority margin was 15%.
Among the 105 patients included in the final analysis, prevention of RCDI was achieved in 96.2% in both the capsule group (51/53) and the colonoscopy group (50/52), thereby meeting the criterion for noninferiority. One patient in each group died of underlying cardiopulmonary illness unrelated to FMT. Minor adverse events occurred in 5.4% of the capsule group, compared with 12.1% in the colonoscopy group. Both groups reported similar improvements in quality of life after FMT.
The patients in the capsule group also seemed to find the experience less unpleasant than those in the colonoscopy group. Although 97% of all patients in the study said they would undergo the assigned delivery method again if necessary, a greater proportion of patients who received FMT via capsule rated their experience as "not at all unpleasant" (66% vs. 44%).
The researchers also noted the cost difference. While FMT via colonoscopy cost $1,120 per patient in Canadian dollars (US $874), FMT by capsule cost CAD $395 per patient (US $308).
"This will transform the way people think about how we deliver fecal microbiota transplant," lead author Dina Kao, MD, a gastroenterologist and professor with the University of Alberta's faculty of medicine and dentistry, said in a University of Alberta news release. "Capsules have numerous advantages over colonoscopy. They are non-invasive, they're less expensive, they don't have any of the risks associated with sedation, and they can be administered in a doctor's office."
Kao said she hopes, based on the results of the study, to begin offering the capsules as an alternative delivery method.
Some questions remain
In an accompanying editorial, JAMA's associate editor and researchers from the University of Michigan Medical School argue that while the results are encouraging, many questions about the overall efficacy of FMT remain, regardless of the delivery method. In particular, they note that FMT has not been proven to be as effective as antibiotics in patients with acute RCDI, and that the optimal timing of FMT after RCDI has not been established.
"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," they write.
FMT is not approved by the US Food and Drug Administration (FDA), but doctors are allowed to use it for patients who are not responding to standard treatment, as long as the patients know it's investigational and are aware of the risks. In March 2016, the FDA issued a draft guidance that would tighten the rules by requiring either the patient receiving FMT or the treating clinician to know the donor. That guidance has yet to be finalized.
Nov 28 JAMA study
Nov 28 JAMA editorial
Nov 28 University of Alberta news release