Ridinilazole versus vancomycin for initial C. difficile infection

Reuters Health Information: Ridinilazole versus vancomycin for initial C. difficile infection

Ridinilazole versus vancomycin for initial C. difficile infection

Last Updated: 2017-05-23

By Scott Baltic

NEW YORK (Reuters Health) - Ridinilazole, a novel, targeted-spectrum antimicrobial, was found to be non-inferior to vancomycin for treating initial Clostridium difficile infection (CDI), according to a study funded by the maker of ridinilazole (Summit Therapeutics, Abingdon, U.K.) and Wellcome Trust.

The primary outcome of the phase 2, double-blind, randomized trial was sustained clinical response rate, defined as clinical cure at the end of treatment and no recurrence of CDI within 30 days, according to the report, published online April 28 by Lancet Infectious Diseases.

One hundred patients with CDI were assigned to receive either oral ridinilazole (200 mg twice daily, plus placebo twice daily) or oral vancomycin (125 mg four times daily) for 10 days. Most participants had mild CDI.

In a modified intention-to-treat population of 69 patients, the rate of sustained clinical response was significantly greater in the ridinilazole group than the vancomycin group (66.7% vs. 42.4%), demonstrating the non-inferiority of ridinilazole.

Ridinilazole’s safety profile was similar to that of vancomycin, although more ridinilazole than vancomycin recipients had adverse events related to metabolism and nutrition disorders (22% vs. 14%) and adverse events related to respiratory, thoracic, and mediastinal disorders (18% vs. 6%).

The authors write that ridinilazole “has the potential to be an effective treatment of C. difficile infection.”

Dr. Richard Vickers, chief scientific officer at Summit Therapeutics and the paper’s lead author, told Reuters Health by email that ridinilazole is expected to enter phase 3 trials in the first half of 2018.

“These trials aim to show the superiority of ridinilazole over the current standard of care, vancomycin, in the endpoint of sustained clinical response as we seek to position ridinilazole for the front-line treatment of CDI,” Vickers said. He added that it’s too early to comment about pricing of the drug, should it reach the market.

In a commentary accompanying the report, Dr. Simon D. Goldenberg of the Centre for Clinical Infection and Diagnostics Research, King’s College London, highlighted some of the study’s limitations: the inclusion of patients slightly younger than those clinicians might expect to see in everyday practice, the study’s low percentage of patients with severe CDI, and the fact that only 21 of 33 study sites recruited patients.

“Discounting these shortcomings, it is rare for a study of an antimicrobial to show statistical superiority over the standard of care,” Goldenberg wrote. “The main advantage of ridinilazole and other new drugs such as fidaxomicin and bezlotoxumab appears to be related to the reduction or prevention of recurrence.”

Dr. Richard L. Nelson of the School of Public Health at the University of Illinois in Chicago, who was the lead author on a March 3 Cochrane review (http://bit.ly/2qeaIoq) of antibiotic treatment of C. difficile-associated diarrhea in adults, told Reuters Health by email that the ridinilazole study has “many deficiencies in its methodology, which make its conclusions pretty weak.”

Those deficiencies, he said, include the study’s small size, its lack of stratification of participants by severity of illness, and what he characterized as “horrible” attrition from the per-protocol group.

“In essence, this is not a randomized trial and should be presented as such,” he said. “This may be a good drug, but there is no way to tell if that is the case from this publication.”

Dr. Nelson surmised, “There is much hoopla about the danger of C. difficile, which is why so many drugs have hit the market, but in fact the problem has been largely solved.” He noted that CDI incidence and mortality rates have fallen in recent years and suggested that better hygiene and isolation have certainly helped. “I think the bug is simply less virulent now than it was 10 years ago,” he said.

SOURCES: http://bit.ly/2qebS3g and http://bit.ly/2qhu1we

Lancet Infect Dis 2017.

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