WASHINGTON – (CDI), according to phase 3 trial results presented at an annual scientific meeting on infectious diseases.
According to the Centers for Disease Control and Prevention, CDI is the top cause of antibiotic-associated diarrhea and one of the most common health care–associated infections in the United States. About 200,000 people in the United States are infected with C. difficile every year in the hospital or clinical care setting.
Most infections are currently treated with vancomycin. Although vancomycin has been shown to be more than 80% effective, it has been linked with recurrence rates ranging from 20% to 30% and interferes with the protective role of the gut microbiome against infection. The current study compared ridinilazole with vancomycin.
Results of the global, double-blinded, randomized trial were presented by Pablo C. Okhuysen, MD, professor of infectious disease at the University of Texas MD Anderson Cancer Center, Houston.
Participants with CDI received a 10-day course of ridinilazole 200 mg twice a day plus placebo or vancomycin 125 mg four times a day. The primary endpoint was sustained clinical response, defined as a clinical response with no recurrent CDI through 30 days after the end of treatment. Recurrent CDI was defined as a new episode of diarrhea with confirmed positive free toxin test requiring additional therapy.
Of the 759 patients enrolled, 745 were included in the modified intention-to-treat population (ridinilazole, n = 370; vancomycin, n = 375). Ridinilazole achieved a numerically higher rate of sustained clinical response than vancomycin (73.0% vs. 70.7%; P = .467), although the difference was not significant. Ridinilazole also resulted in a significant reduction in recurrence rate (8.1% vs. 17.3%; P < .001).
Ridinilazole’s effect was most notable in a subgroup of patients who were not receiving other antibiotics at time of enrollment – about 70% of participants. In that subgroup, the recurrence rate was 6.7% with ridinilazole versus 16.5% with vancomycin (P < .001), Dr. Okhuysen reported.
“That resulted in a relative risk reduction of 60%,” Dr. Okhuysen told this news organization.
Dr. Okhuysen pointed out that there are currently very few treatment options for CDI other than vancomycin.
“We need new agents to treat C. difficile,” he said, “particularly for those at risk of recurrence. In our study, we found that those exposed to vancomycin had very dramatic shifts in their microbiome.”
Vancomycin depletes the gut microbiome, which decreases the conversion of primary acids to secondary bile acids, the researchers noted.
“A dysbiotic microbiome is fertile ground for C. difficile to grow,” Dr. Okhuysen said. Ridinilazole does not disrupt the microbiome, he added.
Ridinilazole was well-tolerated in the study. The proportion of patients with at least one treatment-emergent adverse effect was 36.4% versus 35.5%, respectively, in the ridinilazole and vancomycin groups. And the proportion who stopped treatment because of treatment-related side effects was 0.8% versus 2.9%.
Mary Hayden, MD, pathology director in the division of infectious diseases at Rush University Medical Center, Chicago, who was not involved with the study, said the results are encouraging as “alternative agents or strategies to prevent recurrence are important to reduce CDI morbidity.”
Its double-blind, randomized, multicenter design strengthens the findings, she explained, adding that “the secondary outcomes of higher concentrations of secondary bile acids and microbiota diversity and composition lend biological plausibility.”
Ridinilazole’s narrow spectrum of activity “should result in less disruption of the colonic microbiota, which has theoretical benefit for both reducing CDI recurrence and for reducing risk of acquisition of multidrug-resistant organisms,” Dr. Hayden said.
Dr. Okhuysen shared that the team is in talks with the Food and Drug Administration and is preparing a manuscript for publication.
The study was supported by Summit Pharmaceuticals and funded by the Biomedical and Advanced Research and Development Authority. Dr. Okhuysen has reported receiving research support from and/or consulting for Summit, Merck, Deinove, Melinta, and Ferring Pharmaceuticals. Some of the coauthors have financial relationships with or received research support from Summit. Dr. Hayden has reported no relevant financial relationships.
A version of this article first appeared on.