Efficacy and safety of ridinilazole compared with vancomycin for the treatment of Clostridium difficile infection: a phase 2, randomised, double-blind, active-controlled, non-inferiority study

June 23, 2017 at 7:56 am

Lancet Infectious Diseases July 2017 V.17 N.7

Dr Richard J Vickers, PhD’, Glenn S Tillotson, PhD, Richard Nathan, MD, Sabine Hazan, MD, John Pullman, MD, Christopher Lucasti, DO, Kenneth Deck, MD, Prof Bruce Yacyshyn, MD, Benedict Maliakkal, MD, Yves Pesant, MD, Bina Tejura, MD, Prof David Roblin, FRCP, Prof Dale N Gerding, MD, Prof Mark H Wilcox, MD for the show CoDIFy study group†

Background

Clostridium difficile infection is the most common health-care-associated infection in the USA. We assessed the safety and efficacy of ridinilazole versus vancomycin for treatment of C difficile infection.

Methods

We did a phase 2, randomised, double-blind, active-controlled, non-inferiority study. Participants with signs and symptoms of C difficile infection and a positive diagnostic test result were recruited from 33 centres in the USA and Canada and randomly assigned (1:1) to receive oral ridinilazole (200 mg every 12 h) or oral vancomycin (125 mg every 6 h) for 10 days. The primary endpoint was achievement of a sustained clinical response, defined as clinical cure at the end of treatment and no recurrence within 30 days, which was used to establish non-inferiority (15% margin) of ridinilazole versus vancomycin. The primary efficacy analysis was done on a modified intention-to-treat population comprising all individuals with C difficile infection confirmed by the presence of free toxin in stool who were randomly assigned to receive one or more doses of the study drug. The study is registered with ClinicalTrials.gov, number NCT02092935.

Findings

Between June 26, 2014, and August 31, 2015, 100 patients were recruited; 50 were randomly assigned to receive ridinilazole and 50 to vancomycin. 16 patients did not complete the study, and 11 discontinued treatment early. The primary efficacy analysis included 69 patients (n=36 in the ridinilazole group; n=33 in the vancomycin group). 24 of 36 (66·7%) patients in the ridinilazole group versus 14 of 33 (42·4%) of those in the vancomycin group had a sustained clinical response (treatment difference 21·1%, 90% CI 3·1–39·1, p=0·0004), establishing the non-inferiority of ridinilazole and also showing statistical superiority at the 10% level. Ridinilazole was well tolerated, with an adverse event profile similar to that of vancomycin: 82% (41 of 50) of participants reported adverse events in the ridinilazole group and 80% (40 of 50) in the vancomycin group. There were no adverse events related to ridinilazole that led to discontinuation.

Interpretation

Ridinilazole is a targeted-spectrum antimicrobial that shows potential in treatment of initial C difficile infection and in providing sustained benefit through reduction in disease recurrence. Further clinical development is warranted.

Funding

Wellcome Trust and Summit Therapeutics.

PDF

http://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(17)30235-9.pdf

 

Lancet Infectious Diseases July 2017 V.17 N.7

COMMENT – Expanding the armamentarium for the treatment of Clostridium difficile infection 

Simon D Goldenberg

In The Lancet Infectious Diseases, Richard Vickers and colleagues1 report results of a phase 2 study of ridinilazole, a promising new drug for the treatment of Clostridium difficile infection. Although efforts to improve infection control practices and antimicrobial stewardship have led to significant reductions in some countries, C difficile infection remains a substantial problem worldwide.

All-cause 30-day mortality associated with C difficile infection has been reported to be in the region of 9–38%.3, 4 Furthermore, cases are associated with excess length of hospital stay of approximately 7 days (and 12 days in severe cases). C difficile infection usually occurs following disruption of the intestinal microbiota resulting from exposure to antibiotics. The risk of C difficile infection increases by up to six times during antibiotic therapy and in the month thereafter.

PDF

http://www.thelancet.com/pdfs/journals/laninf/PIIS1473-3099(17)30237-2.pdf

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Entry filed under: Antimicrobianos, Bacterias, Epidemiología, Health Care-Associated Infections, Infecciones gastrointestinales, Infecciones intraabdominales, Infecciones nosocomiales, Metodos diagnosticos, REPORTS, Update.

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