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

Clostridium Difficile Clinical Trial

— EXTEND  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02254967
• Other study ID #: 2819-MA-1002
• Secondary ID: 2013-004619-31
• Status: Completed
• Phase: Phase 4
• Start date: November 6, 2014
• Est. completion date: May 5, 2016

Study information

• Verified date: November 2018
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 364
• Est. completion date: May 5, 2016
• Est. primary completion date: March 27, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Clostridium Difficile

Intervention

Drug:
• Fidaxomicin
oral tablets administered in an extended pulsed regimen
• Vancomycin
oral capsule

Locations

Country	Name	City	State
Austria	Site AT43002	Graz
Austria	Site AT43003	Linz
Austria	Site AT43001	Salzburg
Belgium	Site BE32007	Aalst
Belgium	Site BE32006	Brugge
Belgium	Site BE32001	Brussels
Belgium	Site BE32005	Brussels
Belgium	Site BE32008	Liege
Croatia	Site HR38506	Osijek
Croatia	Site HR38503	Rijeka
Croatia	Site HR38505	Zadar
Croatia	Site HR38501	Zagreb
Czechia	Site CZ42002	Brno-Bohunice
Czechia	Site CZ42005	Kyjov
Czechia	Site CZ42004	Opava
Czechia	Site CZ42003	Praha 5
Czechia	Site CZ42001	Praha 8 - Liben
Denmark	Site DK45001	Herlev
Denmark	Site DK45005	Hillerod
Denmark	Site DK45004	Nykøbing Falster
Finland	Site FI35801	Helsinki
Finland	Site FI35802	Turku
France	Site FR33003	Bordeaux
France	Site FR33008	Clermont- Ferrand Cedex 1
France	Site FR33006	Lille Cedex
France	Site FR33005	Nantes
France	Site FR33004	Nimes
France	Site FR33001	Paris
France	Site FR33007	Paris
France	Site FR33002	Rennes
France	Site FR33009	Saint-Priest en Jarez
Germany	Site DE49012	Hamburg
Germany	Site DE49001	Koeln
Germany	Site DE49011	Köln
Germany	Site DE49006	Leipzig
Germany	Site DE49016	Lübeck
Germany	Site DE49008	Marburg
Greece	Site GR30001	Athens
Greece	Site GR30004	Athens
Greece	Site GR30005	Athens
Greece	Site GR30007	Athens
Greece	Site GR30008	Athens
Greece	Site GR30009	Athens
Greece	Site GR30002	Herakleion, Crete
Greece	Site GR30006	Larisa
Greece	Site GR30010	Thessaloniki
Hungary	Site HU36004	Bekescsaba
Hungary	Site HU36009	Budapest
Hungary	Site HU36010	Budapest
Hungary	Site HU36001	Debrecen
Hungary	Site HU36006	Gyula
Hungary	Site HU36005	Mosonmagyarovar
Hungary	Site HU36008	Orosháza
Hungary	Site HU36007	Pecs
Ireland	Site IE35302	Dublin
Ireland	Site IE35304	Limerick
Italy	Site IT39009	Firenze
Italy	Site IT39005	Genova
Italy	Site IT39004	Milano
Italy	Site IT39003	Monza
Italy	Site IT39007	Napoli
Italy	Site IT39002	Padova
Italy	Site IT39001	Pisa
Italy	Site IT39006	Roma
Italy	Site IT39010	Torino
Poland	Site PL48004	Gdynia
Poland	Site PL48012	Lodz	PL
Poland	Site PL48011	Szczecin
Poland	Site PL48002	Warsaw
Poland	Site PL48008	Warsaw
Poland	Site PL48003	Zgierz
Portugal	Site PT35101	Almada
Portugal	Site PT35102	Amadora
Portugal	Site PT35106	Cotter
Portugal	Site PT35104	Vila Nova de Gaia
Portugal	Site PT35107	Vila Real
Romania	Site RO40001	Bucharest
Romania	Site RO40003	Cluj-Napoca
Romania	Site RO40002	Lasi
Russian Federation	Site RU70001	Moscow
Russian Federation	Site RU70003	Moscow
Slovenia	Site SI38601	Ljubljana
Slovenia	Site SI38605	Ljubljana
Slovenia	Site SI38602	Maribor
Slovenia	Site SI38603	Murska Sobota
Spain	Site ES34003	Barakaldo, Vizcaya
Spain	Site ES34004	Barcelona
Spain	Site ES34005	Madrid
Spain	Site ES34006	Valencia
Sweden	Site SE46002	Göteborg
Sweden	Site SE46004	Jönköping
Sweden	Site SE46001	Lund
Sweden	Site SE46005	Uppsala
Switzerland	Site CH41001	Lugano	Ticino
Switzerland	Site CH41002	St. Gallen
Switzerland	Site CH41004	Zürich
Turkey	Site TR90003	Adana
Turkey	Site TR90002	Ankara
Turkey	Site TR90007	Ankara
Turkey	Site TR90001	Antalya
Turkey	Site TR90006	Eskisehir
Turkey	Site TR90004	Istanbul
Turkey	Site TR90005	Istanbul
United Kingdom	Site GB44008	Blackpool
United Kingdom	Site GB44006	Bristol	UK
United Kingdom	Site GB44005	Cardiff
United Kingdom	Site GB44010	London
United Kingdom	Site GB44003	Sutton in Ashfield	Nottinghamshire
United Kingdom	Site GB44009	Truro

Sponsors (2)

Lead Sponsor	Collaborator
Astellas Pharma Europe Ltd.	Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

Austria,  Belgium,  Croatia,  Czechia,  Denmark,  Finland,  France,  Germany,  Greece,  Hungary,  Ireland,  Italy,  Poland,  Portugal,  Romania,  Russian Federation,  Slovenia,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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
Secondary	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
Secondary	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

External Links

•   Link to results on Astellas Clinical Study Results website