A new study published online in the journal ClinicalInfectious Diseases looked at the use of a non-frozen capsule of microbiome restoration therapy for treating patients with recurrent C. difficile infection.
“Patients with C. difficile are typically managed with antibiotics or fecal transplantation for recurrent C. difficile,” says the study’s author, Sahil Khanna, M.B.B.S., a gastroenterologist at Mayo Clinic. Dr. Khanna says fecal transplantation has been demonstrated to have high success rates by restoring the gut microbiome of patients. However, he says there are several challenges with fecal transplantation including standardization of the product, keeping it frozen, and mitigating the risk of infectious disease transmission during the procedure.
To help reduce the risks, Dr. Khanna and his team studied a transplantation method using a non-frozen capsule instead of whole stool transplantation. An initial dose-finding, the investigator-initiated study looked at the efficacy of different doses of fecal matter and the safety of performing microbiome restoration therapy using an oral product, RBX7455 developed by Rebiotix, Inc. The team found no concerns related to safety.
“Our study has several implications,” says Dr. Khanna. “We think that products like capsules may be able to replace fecal transplantation that is currently done via a colonoscopy. We also think that products that are non-frozen may allow for repeat dosing and for patient-administered self-treatment at home. The good news is that we are moving closer to having safe and effective products to restore the gut microbiome for patients with recurrent C. difficile.”
Dr. Khanna says that larger clinical trials and blinded, placebo-controlled trials are the next step in moving this potential treatment from research into practice.
We are pleased to welcome Dr. Sahil Khanna
as a Member of the C Diff Foundation and Medical Advisory Board.
Dr. Sahil Khanna is an Associate Professor of Medicine in the Division of Gastroenterology and Hepatology at Mayo Clinic, Rochester, MN. He is directing the Comprehensive Gastroenterology Interest group, C. difficile Clinic, Fecal Microbiota Transplantation program and C. difficile related Clinical Trials at Mayo Clinic, Rochester, MN.
He completed Medical School at the All India Institute of Medical Sciences, New Delhi; followed by Post Doctoral Research at University of California San Diego, CA; residency in Internal Medicine and Fellowship in Gastroenterology and Hepatology at Mayo Clinic, Rochester, MN before joining the Faculty. He also completed Masters in Clinical and Translational Sciences during his fellowship. His research and clinical interests include Epidemiology, Outcomes and Emerging Therapeutics for Clostridium difficile infection, an arena in which he has had numerous publications and presentations.
Dr. Khanna has over 100 peer-reviewed publications and serves as reviewer and on the editorial board of several journals. He has won numerous awards including the Miles and Shirley Fiterman Award, Mayo Brothers Distinguished Fellowship Award, Donald C. Balfour Mayo Clinic Alumni Association Research Award, Hartz Foundation Young Investigators’ Scholarship and the Most Distinguished Resident Physician Award from the American Association of Physicians of Indian Origin.
The C Diff Foundation has implemented a global campaign to raise awareness of Clostridium difficile infection (C.difficile) clinical trials,clinical studies, clinical research and observational studies evaluating interventions for C. difficile prevention, treatments, and environmental safety.
In the USA: Nearly half a million Americans suffer from Clostridium difficile (C. diff.) infections in a single year according to a study released in 2015 by the Centers for Disease Control and Prevention (CDC). Approximately 29,000 patients died within 30 days of the initial diagnosis of C. difficile. Of those, about 15,000 deaths were estimated to be directly attributable to C. difficile infections making C. difficile a very important cause of infectious disease death in the United States.
“Clostridium difficile infections are not only the most common cause of healthcare-acquired infections in the United States but also very common in the community in younger patients who previously were thought to be less susceptible to C. difficile. The rate of recurrent C. difficile infections is increasing tremendously and this increase is higher than the rate of primary C. difficile infections,” stated Sahil Khanna, MD, Assistant Professor of Medicine Division of Gastroenterology and Hepatology, Director of the C. difficile Clinic, Fecal Microbiota Transplantation program and C. difficile related Clinical Trials, Mayo Clinic, Rochester, MN.
Dr. Khanna also added, “It is imperative and important for clinical trials to be done to advance the development of new treatments, new medications, and new ways to prevent and treat Clostridium difficile infections.”
Individuals volunteer to participate in clinical trials in hopes of improving their own health, to access treatments that might not be available otherwise, often because they are new and not yet widely available. They help others by contributing to advances in medicine. There can also be potential risks participating in clinical trials and clinical studies. All of the known risks associated with a particular trial and or study will be discussed during the informed consent process. It will be thoroughly explained in the informed consent document that a volunteer will receive from the research staff prior to participating in any study.
To learn more about clinical research (e.g., Clostridium difficile, C.difficile) visit the U.S. Food and Drug Administration http://www.fda.gov or telephone 1-800-835-4709, The National Institutes of Health (NIH) http://www.nih.gov and ClinicalTrials.gov.
“Clinical trials are vital to improving our knowledge about how best to prevent and treat C. difficile infections. Informing patients of clinical trials is important, and in recent years several clinical trials have led to significant improvements in the treatments available for patients with C. difficile infections,” stated Mark Wilcox, MD, FRCPath, Consultant Microbiologist, Head of Microbiology and Academic Lead of Pathology Leeds Teaching Hospitals, Professor of Medical Microbiology University of Leeds Institute of Biomedical and Clinical Sciences, Lead on Clostridium difficile for Public Health England, UK.
About the U.S. Food and Drug Administration (FDA):
The FDA is responsible for protecting the public health by assuring that foods are safe, wholesome, sanitary and properly labeled; ensuring that human and veterinary drug, and vaccines and other biological products and medical devices intended for human use are safe and effective. FDA’s responsibilities extend to the 50 United States, the District of Columbia, Puerto Rico, Guam, the Virgin Islands, American Samoa, and other U.S. territories and possessions.
About the National Institutes of Health (NIH):
The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the nation’s medical research agency making important discoveries that improve health and save lives.
ClinicalTrials.gov is a Web-based resource that provides patients, their family members, health care professionals, researchers, and the public with easy access to information on publicly and privately supported clinical studies on a wide range of diseases and conditions.
According to research, C. Diff is the most common infection in U.S. hospitals within the last decade.
The state of Minnesota has declared November“C. difficile Infection Awareness Month.”According to research, C. Diff is the most common infection in U.S. hospitals within the last decade.
Doctors at Mayo Clinic want people to know that they can get the infection even outside of hospitals. They also say once you get it, it’s easier to get it each time.
Dr. Sahil Khanna said ways to prevent C. diff is to wash hands and avoid unnecessary antibiotics.
He said Mayo Clinic is also studying whether or not there could be a vaccination for C. Diff.
“So there’s a large multi-center study that’s going on right now in people who may be at risk for C. Diff infection,” Khanna said. “So if you’ve been to the hospital, if you’ve received antibiotics, those patients can be enrolled in a vaccine study to see if this vaccine would prevent C. Diff from happening.”
Mayo Clinic is also working with Minnesota-based company Rebiotix on another form of treatment for the infection where people can simply ingest a tablet.
“Newer studies are being derived where you can actually take material from donor stool, process donor stool in a lab, and derive all the good bacteria that you need from the donor stool and put them in capsule form,” Khanna said.
Khanna said this capsule-based treatment has more advantages than a colonoscopy-based treatment that is currently being used to treat C. Diff.
A similar proportion of patients with Clostridium difficile infection showed clinical response at the end of treatment with surotomycin vs. vancomycin in a pivotal phase 3 trial.
However, surotomycin did not demonstrate superiority for key secondary endpoints including sustained clinical response and clinical response over time, and therefore failed to show benefit over vancomycin.
“Surotomycin has a narrow spectrum of activity, demonstrating low resistance rates and rapid activity against C. difficile with similar dose- and time-dependent pharmacodynamics to vancomycin in resolving CDI in a hamster model,” Sahil Khanna, MBBS, of the division of gastroenterology and hepatology at the Mayo Clinic in Rochester, Minn., told Healio Gastroenterology and Liver Disease.
In this second phase 3 trial, “surotomycin demonstrated non-inferiority to vancomycin for CDI clinical response at end of treatment. It was similar to vancomycin for sustained clinical cure.”
In this double-blind, international multicenter trial, Khanna and colleagues randomly assigned 285 patients with confirmed CDI to receive 250 mg oral surotomycin twice daily alternating with placebo twice daily, and 292 to receive 125 mg oral vancomycin four times daily for 10 days.
At the end of treatment, clinical response with surotomycin (83.4%) was non-inferior to vancomycin (82.1%), with a difference of 1.4% (95% CI, 4.9-7.6).
Through 30 to 40 days of follow-up, clinical response over time was not superior to surotomycin, nor was sustained clinical response (63.3% vs. 59%; difference, 4.3%; 95% CI, 3.6-12.2).
Both treatments were generally well tolerated, with typical treatment-emergent adverse events occurring in 52.4% of patients treated with surotomycin and 60.1% of those treated with vancomycin.
“Interestingly, in the hypervirulent strain of CDI, recurrence rate was lower for surotomycin vs. vancomycin,” Khanna said, though he and colleagues noted in the study manuscript that “this finding is nominal due to a lack of multiplicity control.”
Based on the results of these trials, the surotomycin development program has been discontinued, but “the non-inferiority of surotomycin to vancomycin observed in the current trial is in contrast with the parallel trial,” investigators wrote. – by Adam Leitenberger
Disclosures: This study was funded by Merck. Khanna reports he has served as an advisor to Summit Pharmaceuticals and serves as a consultant to Rebiotix and Assembly Biosciences. Please see the full study for a list of all other researchers’ relevant financial disclosures.