A Phase IIIB/IV Study to Compare the Efficacy of Vancomycin Therapy to Extended Duration of Fidaxomicin Therapy in the Clinical Cure of Clostridium Difficile Infection (CDI) in an Older Population

Study Overview
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Brief Summary
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The main objective of the study is to evaluate whether the extended duration fidaxomicin therapy is superior to the standard vancomycin therapy in sustained clinical cure of CDI at 30 days after end of treatment (Day 40 or Day 55).

Official Title
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A Phase IIIB/IV Randomized, Controlled, Open-label, Parallel Group Study to Compare the Efficacy of Vancomycin Therapy to Extended Duration Fidaxomicin Therapy in the Sustained Clinical Cure of Clostridium Difficile Infection in an Older Population

Conditions
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Clostridium Difficile

Intervention / Treatment
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* Drug: Fidaxomicin
* Drug: Vancomycin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CDI is confirmed by clinical symptoms (either > 3 unformed bowel movements or ≥ 200ml of unformed stool (for subjects having rectal collection devices)) in the 24 hours prior to randomization and CDI test confirmed positive for presence of C. difficile toxin A or B in stool within 48 hr prior to randomization. Subject agrees not to participate in another interventional study whilst participating in this study. Exclusion Criteria: Subject is taking or requiring to be treated with prohibited medications Subject has received more than one day of dosing of any therapy for CDI within the last 48 hours Subject has experienced more than 2 previous episodes of CDI in the 3 months prior to study enrolment Subject is unable to swallow oral study medication. Subject has a current diagnosis of toxic megacolon. Subject is not willing to adhere to the provisions of treatment and observation specified in the protocol. Subject has been randomized into this study previously, has taken any investigational drug within 28 days or 5 half lives, whichever is longer, prior to enrollment, or is currently participating in another clinical study which may influence the assessment of efficacy and/or safety endpoints of this study, in the opinion of the Sponsor. Subject has previously participated in a CDI vaccine study Subject has hypersensitivity to fidaxomicin, vancomycin or any of its components.

Ages Eligible for Study
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Minimum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fidaxomicin Extended Pulsed Regimen (EPFX)<br>Participants receive 200 mg fidaxomicin from day 1 to day 5 twice daily, followed by a 1-day gap (day 6) before starting alternate day dosing of 1 tablet of fidaxomicin 200 mg once daily from day 7 to day 25. | Drug: Fidaxomicin<br>* oral tablets administered in an extended pulsed regimen<br>* Other names: Dificid;|
| Experimental: Vancomycin<br>Participants receive 125 mg vancomycin from day 1 to day 10, 4 times daily. | Drug: Vancomycin<br>* oral capsule<br>* Other names: Vancocin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with a Sustained Clinical Cure of CDI at 30 Days after End of Treatment | Sustained clinical cure is defined as an assessment of clinical response at test of cure (TOC; day 12 for vancomycin and day 27 or 12 for EPFX arm) and no recurrence of CDI from TOC until time of assessment. Clinical response is determined by the investigator based on the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) criteria at TOC. Treatment response is present when either stool frequency decreases or stool consistency improves and parameters of disease severity (clinical, laboratory, radiological) improves and no new signs of severe disease develops. | Day 40 (for vancomycin) and day 55 (for fidaxomicin extended pulsed regimen [EPFX]) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with a Sustained Clinical Cure of CDI at Day 40, Day 55 and Day 90 | Sustained clinical cure is defined as an assessment of clinical response at test of cure (TOC; day 12 for vancomycin and day 27 or 12 for EPFX arm) and no recurrence of CDI from TOC until time of assessment. Clinical response is determined by the investigator based on the ESCMID criteria at TOC. Treatment response is present when either stool frequency decreases or stool consistency improves and parameters of disease severity (clinical, laboratory, radiological) improves and no new signs of severe disease develops. | Day 40, 55, 90 | 
| Percentage of Participants with a Clinical Response of CDI at 2 Days after End of Treatment | Clinical response is determined by the investigator based on the ESCMID criteria (i.e., Treatment response is present when either stool frequency decreases or stool consistency improves and parameters of disease severity [clinical, laboratory, radiological] improves and no new signs of severe disease develops. Treatment response should be daily observed and evaluated after at least three days, assuming that the patient is not worsening on treatment) at TOC. | Day 12, 27 | 
| Percentage of Participants with a Clinical Response of CDI at Day 12 | Clinical response is determined by the investigator based on the ESCMID criteria (i.e., Treatment response is present when either stool frequency decreases or stool consistency improves and parameters of disease severity [clinical, laboratory, radiological] improves and no new signs of severe disease develops. Treatment response should be daily observed and evaluated after at least three days, assuming that the participant is not worsening on treatment) at TOC. | Day 12 | 
| Number of Participants with a Relapse on Day 90 as Determined by Whole Genome Sequencing of C. Difficile Isolates | For participants with a recurrence after TOC, whole genome sequencing of isolates is performed on paired samples from day 1 and the day of the confirmed recurrence. Relapse is defined as paired isolates from a single recurrent participant with ≤ 2 single nucleotide variations (SNVs). | Baseline through day 90 | 
| Time to Resolution of Diarrhea (TTROD) | Time to resolution of diarrhea is defined as the time elapsing (in hours rounded up from minutes > 30) from the start of treatment (time of first dose of study drug) to resolution of diarrhea (time of the last unformed bowel movement [UBM] the day prior to the first of 2 consecutive days of ≤ 3 UBMs, > 50% reduction in number of stools or > 75% reduction in volume of liquid stool) that are sustained through to TOC. | Up to day 10 (for vancomycin) or up to day 25 (for EPFX) | 
| Percentage of Participants with a Recurrence of CDI at Day 40, Day 55 and Day 90 | For participants with clinical response at TOC, recurrence of CDI is defined as re-establishment of diarrhea after TOC to an extent (judged by the frequency of passed UBMs) that is greater than the frequency recorded on day 10 for vancomycin arm or day 25 for EPFX arm (2 days prior to TOC), confirmed by a CDI test positive for Toxin A/B and requiring further CDI therapy. | Day 40, 55, 90 | 
| Time to Recurrence of CDI after End of Active Treatment | Time to recurrence of CDI is defined as the time in days from clinical response until onset of recurrence of CDI for participants who respond at TOC. | From day 10 up to day 90 | 
| Disease-free Survival After Day 10 | Disease-free survival is defined as the time in days a participant does not have symptoms of diarrhea from day 10 up to day 90 for participants who respond at TOC. | From day 10 up to day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aged, Fidaxomicin, Clostridium Difficile, Vancomycin