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
- Registration Number
- NCT02254967
- Lead Sponsor
- Astellas Pharma Europe Ltd.
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 364
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Fidaxomicin Extended Pulsed Regimen (EPFX) Fidaxomicin 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. Vancomycin Vancomycin Participants receive 125 mg vancomycin from day 1 to day 10, 4 times daily.
- Primary Outcome Measures
Name Time Method Percentage of Participants with a Sustained Clinical Cure of CDI at 30 Days after End of Treatment Day 40 (for vancomycin) and day 55 (for fidaxomicin extended pulsed regimen [EPFX]) 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.
- Secondary Outcome Measures
Name Time Method Disease-free Survival After Day 10 From day 10 up to day 90 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.
Percentage of Participants with a Clinical Response of CDI at Day 12 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.
Percentage of Participants with a Recurrence of CDI at Day 40, Day 55 and Day 90 Day 40, 55, 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.
Time to Recurrence of CDI after End of Active Treatment From day 10 up to day 90 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.
Number of Participants with a Relapse on Day 90 as Determined by Whole Genome Sequencing of C. Difficile Isolates Baseline through day 90 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).
Percentage of Participants with a Sustained Clinical Cure of CDI at Day 40, Day 55 and Day 90 Day 40, 55, 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.
Percentage of Participants with a Clinical Response of CDI at 2 Days after End of Treatment Day 12, 27 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.
Time to Resolution of Diarrhea (TTROD) Up to day 10 (for vancomycin) or up to day 25 (for EPFX) 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.
Trial Locations
- Locations (109)
Site HU36010
🇭🇺Budapest, Hungary
Site GR30007
🇬🇷Athens, Greece
Site GR30004
🇬🇷Athens, Greece
Site HU36004
🇭🇺Bekescsaba, Hungary
Site PL48004
🇵🇱Gdynia, Poland
Site PL48002
🇵🇱Warsaw, Poland
Site RO40003
🇷🇴Cluj-Napoca, Romania
Site RU70001
🇷🇺Moscow, Russian Federation
Site PT35102
🇵🇹Amadora, Portugal
Site TR90005
🇹🇷Istanbul, Turkey
Site HU36006
🇭🇺Gyula, Hungary
Site PL48003
🇵🇱Zgierz, Poland
Site GR30001
🇬🇷Athens, Greece
Site HR38505
🇭🇷Zadar, Croatia
Site DK45004
🇩🇰Nykøbing Falster, Denmark
Site CZ42004
🇨🇿Opava, Czechia
Site BE32006
🇧🇪Brugge, Belgium
Site BE32001
🇧🇪Brussels, Belgium
Site FR33003
🇫🇷Bordeaux, France
Site CZ42001
🇨🇿Praha 8 - Libeň, Czechia
Site DE49012
🇩🇪Hamburg, Germany
Site DE49008
🇩🇪Marburg, Germany
Site BE32007
🇧🇪Aalst, Belgium
Site HR38501
🇭🇷Zagreb, Croatia
Site DE49001
🇩🇪Koeln, Germany
Site CZ42003
🇨🇿Praha 5, Czechia
Site HU36001
🇭🇺Debrecen, Hungary
Site HR38503
🇭🇷Rijeka, Croatia
Site IT39006
🇮🇹Roma, Italy
Site IT39009
🇮🇹Firenze, Italy
Site HU36005
🇭🇺Mosonmagyarovar, Hungary
Site PT35106
🇵🇹Cotter, Portugal
Site RO40001
🇷🇴Bucharest, Romania
Site SI38603
🇸🇮Murska Sobota, Slovenia
Site DE49011
🇩🇪Köln, Germany
Site IT39003
🇮🇹Monza, Italy
Site FR33005
🇫🇷Nantes, France
Site CH41004
🇨🇭Zürich, Switzerland
Site TR90002
🇹🇷Ankara, Turkey
Site FI35801
🇫🇮Helsinki, Finland
Site FI35802
🇫🇮Turku, Finland
Site GR30008
🇬🇷Athens, Greece
Site GR30002
🇬🇷Herakleion, Crete, Greece
Site GR30006
🇬🇷Larisa, Greece
Site PL48012
🇵🇱Lodz, PL, Poland
Site FR33004
🇫🇷Nimes, France
Site HU36009
🇭🇺Budapest, Hungary
Site CZ42005
🇨🇿Kyjov, Czechia
Site DE49016
🇩🇪Lübeck, Germany
Site ES34004
🇪🇸Barcelona, Spain
Site ES34006
🇪🇸Valencia, Spain
Site GR30009
🇬🇷Athens, Greece
Site HU36008
🇭🇺Orosháza, Hungary
Site HU36007
🇭🇺Pecs, Hungary
Site TR90006
🇹🇷Eskisehir, Turkey
Site IT39007
🇮🇹Napoli, Italy
Site IT39002
🇮🇹Padova, Italy
Site FR33009
🇫🇷Saint-Priest en Jarez, France
Site FR33001
🇫🇷Paris, France
Site IT39001
🇮🇹Pisa, Italy
Site IE35302
🇮🇪Dublin, Ireland
Site IE35304
🇮🇪Limerick, Ireland
Site PL48008
🇵🇱Warsaw, Poland
Site PT35101
🇵🇹Almada, Portugal
Site PT35107
🇵🇹Vila Real, Portugal
Site RO40002
🇷🇴Lasi, Romania
Site SI38602
🇸🇮Maribor, Slovenia
Site CH41001
🇨🇭Lugano, Ticino, Switzerland
Site PL48011
🇵🇱Szczecin, Poland
Site SI38601
🇸🇮Ljubljana, Slovenia
Site TR90007
🇹🇷Ankara, Turkey
Site IT39010
🇮🇹Torino, Italy
Site SE46002
🇸🇪Göteborg, Sweden
Site SE46004
🇸🇪Jönköping, Sweden
Site GB44006
🇬🇧Bristol, UK, United Kingdom
Site SI38605
🇸🇮Ljubljana, Slovenia
Site TR90003
🇹🇷Adana, Turkey
Site GB44010
🇬🇧London, United Kingdom
Site SE46001
🇸🇪Lund, Sweden
Site SE46005
🇸🇪Uppsala, Sweden
Site ES34003
🇪🇸Barakaldo, Vizcaya, Spain
Site ES34005
🇪🇸Madrid, Spain
Site CH41002
🇨🇭St. Gallen, Switzerland
Site TR90004
🇹🇷Istanbul, Turkey
Site TR90001
🇹🇷Antalya, Turkey
Site FR33002
🇫🇷Rennes, France
Site GB44005
🇬🇧Cardiff, United Kingdom
Site GB44009
🇬🇧Truro, United Kingdom
Site DE49006
🇩🇪Leipzig, Germany
Site FR33007
🇫🇷Paris, France
Site AT43002
🇦🇹Graz, Austria
Site AT43003
🇦🇹Linz, Austria
Site AT43001
🇦🇹Salzburg, Austria
Site BE32005
🇧🇪Brussels, Belgium
Site BE32008
🇧🇪Liege, Belgium
Site HR38506
🇭🇷Osijek, Croatia
Site CZ42002
🇨🇿Brno-Bohunice, Czechia
Site DK45001
🇩🇰Herlev, Denmark
Site DK45005
🇩🇰Hillerod, Denmark
Site FR33008
🇫🇷Clermont- Ferrand Cedex 1, France
Site FR33006
🇫🇷Lille Cedex, France
Site GR30005
🇬🇷Athens, Greece
Site GR30010
🇬🇷Thessaloniki, Greece
Site IT39004
🇮🇹Milano, Italy
Site IT39005
🇮🇹Genova, Italy
Site PT35104
🇵🇹Vila Nova de Gaia, Portugal
Site RU70003
🇷🇺Moscow, Russian Federation
Site GB44008
🇬🇧Blackpool, United Kingdom
Site GB44003
🇬🇧Sutton in Ashfield, Nottinghamshire, United Kingdom