Clinical trial NCT02254967: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Clostridium Difficile
Keywords: Aged
Fidaxomicin
Clostridium Difficile
Vancomycin
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2014-10-02
Enrollment: 364
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants with a Sustained Clinical Cure of CDI at 30 Days after End of Treatment
timeFrame: Day 40 (for vancomycin) and day 55 (for fidaxomicin extended pulsed regimen [EPFX])
Secondary outcomes:
measure: Percentage of Participants with a Sustained Clinical Cure of CDI at Day 40, Day 55 and Day 90
timeFrame: Day 40, 55, 90
measure: Percentage of Participants with a Clinical Response of CDI at 2 Days after End of Treatment
timeFrame: Day 12, 27
measure: Percentage of Participants with a Clinical Response of CDI at Day 12
timeFrame: Day 12
measure: Number of Participants with a Relapse on Day 90 as Determined by Whole Genome Sequencing of C. Difficile Isolates
timeFrame: Baseline through day 90
measure: Time to Resolution of Diarrhea (TTROD)
timeFrame: Up to day 10 (for vancomycin) or up to day 25 (for EPFX)
measure: Percentage of Participants with a Recurrence of CDI at Day 40, Day 55 and Day 90
timeFrame: Day 40, 55, 90
measure: Time to Recurrence of CDI after End of Active Treatment
timeFrame: From day 10 up to day 90
measure: Disease-free Survival After Day 10
timeFrame: From day 10 up to day 90
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Site AT43002
city: Linz
country: Austria
facility: Site AT43003
city: Salzburg
country: Austria
facility: Site AT43001
city: Aalst
country: Belgium
facility: Site BE32007
city: Brugge
country: Belgium
facility: Site BE32006
city: Brussels
country: Belgium
facility: Site BE32001
city: Brussels
country: Belgium
facility: Site BE32005
city: Liege
country: Belgium
facility: Site BE32008
city: Osijek
country: Croatia
facility: Site HR38506
city: Rijeka
country: Croatia
facility: Site HR38503
city: Zadar
country: Croatia
facility: Site HR38505
city: Zagreb
country: Croatia
facility: Site HR38501
city: Brno-Bohunice
country: Czechia
facility: Site CZ42002
city: Kyjov
country: Czechia
facility: Site CZ42005
city: Opava
country: Czechia
facility: Site CZ42004
city: Praha 5
country: Czechia
facility: Site CZ42003
city: Praha 8 - Libeň
country: Czechia
facility: Site CZ42001
city: Herlev
country: Denmark
facility: Site DK45001
city: Hillerod
country: Denmark
facility: Site DK45005
city: Nykøbing Falster
country: Denmark
facility: Site DK45004
city: Helsinki
country: Finland
facility: Site FI35801
city: Turku
country: Finland
facility: Site FI35802
city: Bordeaux
country: France
facility: Site FR33003
city: Clermont- Ferrand Cedex 1
country: France
facility: Site FR33008
city: Lille Cedex
country: France
facility: Site FR33006
city: Nantes
country: France
facility: Site FR33005
city: Nimes
country: France
facility: Site FR33004
city: Paris
country: France
facility: Site FR33001
city: Paris
country: France
facility: Site FR33007
city: Rennes
country: France
facility: Site FR33002
city: Saint-Priest en Jarez
country: France
facility: Site FR33009
city: Hamburg
country: Germany
facility: Site DE49012
city: Koeln
country: Germany
facility: Site DE49001
city: Köln
country: Germany
facility: Site DE49011
city: Leipzig
country: Germany
facility: Site DE49006
city: Lübeck
country: Germany
facility: Site DE49016
city: Marburg
country: Germany
facility: Site DE49008
city: Athens
country: Greece
facility: Site GR30005
city: Athens
country: Greece
facility: Site GR30008
city: Athens
country: Greece
facility: Site GR30001
city: Athens
country: Greece
facility: Site GR30004
city: Athens
country: Greece
facility: Site GR30009
city: Athens
country: Greece
facility: Site GR30007
city: Herakleion, Crete
country: Greece
facility: Site GR30002
city: Larisa
country: Greece
facility: Site GR30006
city: Thessaloniki
country: Greece
facility: Site GR30010
city: Bekescsaba
country: Hungary
facility: Site HU36004
city: Budapest
country: Hungary
facility: Site HU36010
city: Budapest
country: Hungary
facility: Site HU36009
city: Debrecen
country: Hungary
facility: Site HU36001
city: Gyula
country: Hungary
facility: Site HU36006
city: Mosonmagyarovar
country: Hungary
facility: Site HU36005
city: Orosháza
country: Hungary
facility: Site HU36008
city: Pecs
country: Hungary
facility: Site HU36007
city: Dublin
country: Ireland
facility: Site IE35302
city: Limerick
country: Ireland
facility: Site IE35304
city: Firenze
country: Italy
facility: Site IT39009
city: Genova
country: Italy
facility: Site IT39005
city: Milano
country: Italy
facility: Site IT39004
city: Monza
country: Italy
facility: Site IT39003
city: Napoli
country: Italy
facility: Site IT39007
city: Padova
country: Italy
facility: Site IT39002
city: Pisa
country: Italy
facility: Site IT39001
city: Roma
country: Italy
facility: Site IT39006
city: Torino
country: Italy
facility: Site IT39010
city: Lodz
country: Poland
facility: Site PL48012
state: PL
city: Gdynia
country: Poland
facility: Site PL48004
city: Szczecin
country: Poland
facility: Site PL48011
city: Warsaw
country: Poland
facility: Site PL48008
city: Warsaw
country: Poland
facility: Site PL48002
city: Zgierz
country: Poland
facility: Site PL48003
city: Almada
country: Portugal
facility: Site PT35101
city: Amadora
country: Portugal
facility: Site PT35102
city: Cotter
country: Portugal
facility: Site PT35106
city: Vila Nova de Gaia
country: Portugal
facility: Site PT35104
city: Vila Real
country: Portugal
facility: Site PT35107
city: Bucharest
country: Romania
facility: Site RO40001
city: Cluj-Napoca
country: Romania
facility: Site RO40003
city: Lasi
country: Romania
facility: Site RO40002
city: Moscow
country: Russian Federation
facility: Site RU70001
city: Moscow
country: Russian Federation
facility: Site RU70003
city: Ljubljana
country: Slovenia
facility: Site SI38601
city: Ljubljana
country: Slovenia
facility: Site SI38605
city: Maribor
country: Slovenia
facility: Site SI38602
city: Murska Sobota
country: Slovenia
facility: Site SI38603
city: Barakaldo, Vizcaya
country: Spain
facility: Site ES34003
city: Barcelona
country: Spain
facility: Site ES34004
city: Madrid
country: Spain
facility: Site ES34005
city: Valencia
country: Spain
facility: Site ES34006
city: Göteborg
country: Sweden
facility: Site SE46002
city: Jönköping
country: Sweden
facility: Site SE46004
city: Lund
country: Sweden
facility: Site SE46001
city: Uppsala
country: Sweden
facility: Site SE46005
city: Lugano
country: Switzerland
facility: Site CH41001
state: Ticino
city: St. Gallen
country: Switzerland
facility: Site CH41002
city: Zürich
country: Switzerland
facility: Site CH41004
city: Adana
country: Turkey
facility: Site TR90003
city: Ankara
country: Turkey
facility: Site TR90002
city: Ankara
country: Turkey
facility: Site TR90007
city: Antalya
country: Turkey
facility: Site TR90001
city: Eskisehir
country: Turkey
facility: Site TR90006
city: Istanbul
country: Turkey
facility: Site TR90005
city: Istanbul
country: Turkey
facility: Site TR90004
city: Sutton in Ashfield
country: United Kingdom
facility: Site GB44003
state: Nottinghamshire
city: Bristol
country: United Kingdom
facility: Site GB44006
state: UK
city: Blackpool
country: United Kingdom
facility: Site GB44008
city: Cardiff
country: United Kingdom
facility: Site GB44005
city: London
country: United Kingdom
facility: Site GB44010
city: Truro
country: United Kingdom
facility: Site GB44009
Study officials:
affiliation: Astellas Pharma Europe Ltd.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Cornely OA, Vehreschild MJGT, Adomakoh N, Georgopali A, Karas A, Kazeem G, Guery B. Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection: EXTEND study subgroup analyses. Eur J Clin Microbiol Infect Dis. 2019 Jun;38(6):1187-1194. doi: 10.1007/s10096-019-03525-y. Epub 2019 Mar 25.
citation: Guery B, Menichetti F, Anttila VJ, Adomakoh N, Aguado JM, Bisnauthsing K, Georgopali A, Goldenberg SD, Karas A, Kazeem G, Longshaw C, Palacios-Fabrega JA, Cornely OA, Vehreschild MJGT; EXTEND Clinical Study Group. Extended-pulsed fidaxomicin versus vancomycin for Clostridium difficile infection in patients 60 years and older (EXTEND): a randomised, controlled, open-label, phase 3b/4 trial. Lancet Infect Dis. 2018 Mar;18(3):296-307. doi: 10.1016/S1473-3099(17)30751-X. Epub 2017 Dec 19.