Clinical trial NCT01983683: Efficacy and Safety of Cadazolid Versus Vancomycin in Subjects With Clostridium Difficile-associated Diarrhea
Official title: A Multi-center, Randomized, Double-blind Study to Compare the Efficacy and Safety of Cadazolid Versus Vancomycin in Subjects With Clostridium Difficile-associated Diarrhea (CDAD).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Clostridium Difficile Infection
Keywords: Clostridium difficile infection
Post-antibiotic diarrhea
Lead sponsor: Actelion
Sponsor class: INDUSTRY
First posted: 2013-11-14
Enrollment: 631
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This clinical study is conducted to assess the efficacy of cadazolid compared to vancomycin in subjects with Clostridium difficile-associated diarrhea (CDAD).

Detailed description: Subjects selected to participate in the study are treated either with cadazolid or vancomycin for 10 days. At the end of treatment, clinical cure is assessed; subjects are then followed-up to assess any disease recurrence.

Eligibility criteria: Inclusion Criteria:

* Signed Informed Consent.
* Male or female ≥ 18 years of age. Females of childbearing potential must agree to use an adequate and reliable method of contraception.
* Subject with a diagnosis of mild-moderate or severe CDAD (first occurrence or first recurrence within 3 months) with: Diarrhea: a change in bowel habits with \> 3 liquid or unformed bowel movements (UBM) within 24 hours prior to randomization, AND Positive C. difficile toxin test on a stool sample produced within 72 hours prior to randomization.

Exclusion Criteria:

* More than one previous episode of CDAD in the 3-month period prior to randomization.
* Evidence of life-threatening or fulminant CDAD.
* Likelihood of death within 72 hours from any cause.
* History of inflammatory colitides, chronic abdominal pain, or chronic diarrhea.
* Antimicrobial treatment active against CDAD administered for \> 24 hours except for metronidazole treatment failures (MTF)
* Known hypersensitivity or contraindication to study drugs, oxazolidinones, or quinolones.
* Unable or unwilling to comply with all protocol requirements.
* Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol

Primary outcomes:
measure: Clinical Cure Rate (CCR) in the Modified Intent-to-treat Population
timeFrame: Up to Day 12 on average (end-of-treatment + 2 days)
measure: Clinical Cure Rate (CCR) in the Per-protocol Population
timeFrame: Up to Day 12 on average (end-of-treatment + 2 days)
Secondary outcomes:
measure: Sustained Cure Rate (SCR) in the Modified Intent-to-treat Population
timeFrame: Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days)
measure: Kaplan-Meier Estimates for Resolution of Diarrhea (ROD)
timeFrame: Up to Day 10
measure: Change From Baseline to Day 3 in Clostridium Difficile Infection (CDI) Daily Symptoms Patient-Reported Outcome (CDI-DaySyms PRO) Domain Scores
timeFrame: Baseline to End of Treatment (10 days after starting study drug) + 2 days
Other outcomes:
measure: Investigator's Assessment of Clinical Response (ICR) Rate at Visit 4 in the Modified Intent-to-treat Population
timeFrame: Up to Day 12 on average (up to end-of-treatment + 2 to 4 days)
measure: Investigator's Assessment of Clinical Response (ICR) Rate at Visit 4 in the Per-protocol Population
timeFrame: Up to Day 12 on average (up to end-of-treatment + 2 to 4 days)
measure: Investigator's Assessment of Sustained Response Rate (ISR Rate) at Visit 5
timeFrame: Between Day 38 and Day 42 on average (end-of-treatment + 28 to 32 days)
measure: Sustained Cure Rate (SCR) in the Per-protocol Population
timeFrame: Between Day 38 and Day 42 on average (end-of-treatment + 28-32 days)
measure: Recurrence Rate
timeFrame: Between Day 13 and Day 40 on average (from end-of-treatment + 3 days and end-of-treatment + 30 days)
Locations:
Study officials:
affiliation: Actelion
name: Anne Claire Marrast, MD
role: STUDY_DIRECTOR
References:
citation: Gerding DN, Cornely OA, Grill S, Kracker H, Marrast AC, Nord CE, Talbot GH, Buitrago M, Gheorghe Diaconescu I, Murta de Oliveira C, Preotescu L, Pullman J, Louie TJ, Wilcox MH. Cadazolid for the treatment of Clostridium difficile infection: results of two double-blind, placebo-controlled, non-inferiority, randomised phase 3 trials. Lancet Infect Dis. 2019 Mar;19(3):265-274. doi: 10.1016/S1473-3099(18)30614-5. Epub 2019 Jan 29.
citation: Kleinman L, Talbot GH, Hunsche E, Schuler R, Nord CE. The CDI-DaySyms: Content Development of a New Patient-Reported Outcome Questionnaire for Symptoms of Clostridium difficile Infection. Value Health. 2018 Apr;21(4):441-448. doi: 10.1016/j.jval.2017.08.3017. Epub 2017 Nov 7.