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

CoDIFy study group

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)735-744
Number of pages10
JournalThe Lancet Infectious Diseases
Volume17
Issue number7
DOIs
StatePublished - Jul 1 2017

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Clostridium Infections
Clostridium difficile
Vancomycin
Safety
Therapeutics
Infection
Recurrence
Cross Infection
Routine Diagnostic Tests
Signs and Symptoms
Canada

ASJC Scopus subject areas

  • Infectious Diseases

Cite this

@article{3225326bd22348d7aed04e8aad9cf727,
title = "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",
abstract = "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.",
author = "{CoDIFy study group} and Vickers, {Richard J.} and Tillotson, {Glenn S.} and Richard Nathan and Sabine Hazan and John Pullman and Christopher Lucasti and Kenneth Deck and Bruce Yacyshyn and Benedict Maliakkal and Yves Pesant and Bina Tejura and David Roblin and Gerding, {Dale N.} and Wilcox, {Mark H.} and Amit Bhan and Wayne Campbell and Teena Chopra and Kenneth Deck and Yoav Golan and Ian Gordon and Ravi Kamepalli and Sahil Khanna and Christine Lee and Christopher Lucasti and Benedict Maliakkal and Irene Minang and Kathleen Mullane and Richard Nathan and Matthew Oughton and Yves Pesant and John Phillips and John Pullman and Riska, {Paul F.} and Christian Schrock and Jonathan Siegel and Alon Steinberg and David Talan and Stephen Tamang and Michael Tan and Karl Weiss and Chia Wang and Bruce Yacyshyn and Young, {Jo Anne} and Jonathan Zenilman",
year = "2017",
month = "7",
day = "1",
doi = "10.1016/S1473-3099(17)30235-9",
language = "English (US)",
volume = "17",
pages = "735--744",
journal = "The Lancet Infectious Diseases",
issn = "1473-3099",
publisher = "Lancet Publishing Group",
number = "7",

}

TY - JOUR

T1 - Efficacy and safety of ridinilazole compared with vancomycin for the treatment of Clostridium difficile infection

T2 - a phase 2, randomised, double-blind, active-controlled, non-inferiority study

AU - CoDIFy study group

AU - Vickers, Richard J.

AU - Tillotson, Glenn S.

AU - Nathan, Richard

AU - Hazan, Sabine

AU - Pullman, John

AU - Lucasti, Christopher

AU - Deck, Kenneth

AU - Yacyshyn, Bruce

AU - Maliakkal, Benedict

AU - Pesant, Yves

AU - Tejura, Bina

AU - Roblin, David

AU - Gerding, Dale N.

AU - Wilcox, Mark H.

AU - Bhan, Amit

AU - Campbell, Wayne

AU - Chopra, Teena

AU - Deck, Kenneth

AU - Golan, Yoav

AU - Gordon, Ian

AU - Kamepalli, Ravi

AU - Khanna, Sahil

AU - Lee, Christine

AU - Lucasti, Christopher

AU - Maliakkal, Benedict

AU - Minang, Irene

AU - Mullane, Kathleen

AU - Nathan, Richard

AU - Oughton, Matthew

AU - Pesant, Yves

AU - Phillips, John

AU - Pullman, John

AU - Riska, Paul F.

AU - Schrock, Christian

AU - Siegel, Jonathan

AU - Steinberg, Alon

AU - Talan, David

AU - Tamang, Stephen

AU - Tan, Michael

AU - Weiss, Karl

AU - Wang, Chia

AU - Yacyshyn, Bruce

AU - Young, Jo Anne

AU - Zenilman, Jonathan

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

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