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2017 ; 17
(7
): 735-744
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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
#MMPMID28461207
Vickers RJ
; Tillotson GS
; Nathan R
; Hazan S
; Pullman J
; Lucasti C
; Deck K
; Yacyshyn B
; Maliakkal B
; Pesant Y
; Tejura B
; Roblin D
; Gerding DN
; Wilcox MH
Lancet Infect Dis
2017[Jul]; 17
(7
): 735-744
PMID28461207
show ga
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.