New C Difficile Infection Study Expands the Patient Pool

Cases were identified by searching the Veterans Affairs Corporate Data Warehouse.

A novel study with a home-based enrollment is looking at the efficacy of microbiota treatments for Clostridioides difficile infections (CDI) following successful antimicrobial therapy.

A team, led by Dimitri M. Drekonja, Minneapolis Veterans Affairs Health Care System, conducted a Veterans Affairs-wide randomized controlled trial utilizing centralized case identification, with enrollment and fecal microbiota transplant administration occurring in the patient’s home.

Recurrent CDI

Currently, the leading cause of infectious diarrhea in the US is C difficile infections. This comes with a significant morbidity and mortality risk.

Recurrent infections can be especially challenging because each recurrence increases the likelihood of a successive recurrence, which could lead to cycles of prolonged symptoms, frequent antimicrobial use, and decreased quality of life. One way to prevent this is fecal microbiota transplantation.

However, this has only been tested in observational studies with conflicting results from randomized controlled trials.

New Trial Design

The type of trial design in the VA study should significantly improve trial efficiency, greatly decrease cost, increase consistency of trial administration, and make nationwide clinical trials for less common diseases more advantageous.

In the study, the researchers compared capsule-delivered fecal microbiota transplant for the prevention of recurrent CDI, administered following successful initial treatment of recurrent C difficile infections with standard treatment.

The investigators are seeking primary endpoint of the incidence of recurrent CDI or death. They identified cases by searching the Veterans Affairs Corporate Data Warehouse.

Enrollment

Central study coordinators then reached out to the identified patients who met the inclusion criteria, 102 of which were enrolled in the trial through January 2021.

For those who signed onto the study, they were scheduled for in-home consent, randomization, and capsule administration, followed by telephone follow-up for 6 additional months.

Centralized case identified and in-home enrolled enabled the investigators to enroll patients from 34 states. In addition, 38% of the patient population was from rural or highly rural areas.

“Centralized case identification and in-home enrollment is a feasible and innovative method of conducting randomized controlled trials in the Veterans Affairs system, improving access to clinical research for populations who may have difficulty engaging with the traditional model of clinical trials where enrollment is based at large hospitals in major metropolitan areas,” the authors wrote.

The Risk of CDI

Recently, investigators found gut microbiome manipulation could help reduce the risk of CDI.

C difficile infections disproportionally affect geriatric patients, particularly those living in nursing homes. The rate of CDI is several fold higher in individuals 65 years of age and older with an increased risk of 2% for each additional year after 65 years. Elderly patients also have higher rates of recurrence, complications, and death.

An average of 40-50% of new CDI cases are attributed to nursing home settings.

Further analysis of the positive samples were characterized by increased abundances of pathogenic or inflammatory-associated bacterial taxa and by lower abundances of taxa with anti-inflammatory or symbiotic properties.

Residents treated with proton pump inhibitors had a lower prevalence of C difficile (OR, 0.46; 95% CI, 0.22-0.99), while the abundance of bacterial species with known beneficial effects were higher in PPI users and lower in individuals with high C difficile prevalence.

The study, “Microbiota or placebo after antimicrobial therapy for recurrent Clostridioides difficile at home: A clinical trial with novel home-based enrollment,” was published online in Clinical Trials.