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 (EXTEND)

October 29, 2024 updated by: Astellas Pharma Europe Ltd.

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

364

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Graz, Austria, 8020
        • Site AT43002
      • Linz, Austria, 4010
        • Site AT43003
      • Salzburg, Austria, 5020
        • Site AT43001
  • Belgium
      • Aalst, Belgium, 9300
        • Site BE32007
      • Brugge, Belgium, B-8000
        • Site BE32006
      • Brussels, Belgium, 1000
        • Site BE32001
      • Brussels, Belgium, B-1020
        • Site BE32005
      • Liege, Belgium, 4000
        • Site BE32008
  • Croatia
      • Osijek, Croatia, 31000
        • Site HR38506
      • Rijeka, Croatia, 51000
        • Site HR38503
      • Zadar, Croatia, 23 000
        • Site HR38505
      • Zagreb, Croatia, 10000
        • Site HR38501
  • Czechia
      • Brno-Bohunice, Czechia, 62500
        • Site CZ42002
      • Kyjov, Czechia, 69733
        • Site CZ42005
      • Opava, Czechia, 74601
        • Site CZ42004
      • Praha 5, Czechia, 15006
        • Site CZ42003
      • Praha 8 - Libeň, Czechia, 18081
        • Site CZ42001
  • Denmark
      • Herlev, Denmark, 2730
        • Site DK45001
      • Hillerod, Denmark, 3400
        • Site DK45005
      • Nykøbing Falster, Denmark, 4800
        • Site DK45004
  • Finland
      • Helsinki, Finland, 00029
        • Site FI35801
      • Turku, Finland, 20521
        • Site FI35802
  • France
      • Bordeaux, France, 33000
        • Site FR33003
      • Clermont- Ferrand Cedex 1, France, 63003
        • Site FR33008
      • Lille Cedex, France, 59037
        • Site FR33006
      • Nantes, France, 44000
        • Site FR33005
      • Nimes, France, 30000
        • Site FR33004
      • Paris, France, 75010
        • Site FR33001
      • Paris, France, 75012
        • Site FR33007
      • Rennes, France, 35037
        • Site FR33002
      • Saint-Priest en Jarez, France, 42270
        • Site FR33009
  • Germany
      • Hamburg, Germany, 25599
        • Site DE49012
      • Koeln, Germany, 50937
        • Site DE49001
      • Köln, Germany, 51067
        • Site DE49011
      • Leipzig, Germany, 04103
        • Site DE49006
      • Lübeck, Germany, 23538
        • Site DE49016
      • Marburg, Germany, 35043
        • Site DE49008
  • Greece
      • Athens, Greece, 11527
        • Site GR30004
      • Athens, Greece, 10675
        • Site GR30005
      • Athens, Greece, 115 25
        • Site GR30008
      • Athens, Greece, 11527
        • Site GR30001
      • Athens, Greece, 12461
        • Site GR30009
      • Athens, Greece, 14561
        • Site GR30007
      • Herakleion, Crete, Greece, 70013
        • Site GR30002
      • Larisa, Greece, 41221
        • Site GR30006
      • Thessaloniki, Greece, 546 36
        • Site GR30010
  • Hungary
      • Bekescsaba, Hungary, H-5600
        • Site HU36004
      • Budapest, Hungary, 1082
        • Site HU36010
      • Budapest, Hungary, 1088
        • Site HU36009
      • Debrecen, Hungary, H-4043
        • Site HU36001
      • Gyula, Hungary, H-5700
        • Site HU36006
      • Mosonmagyarovar, Hungary, H-9200
        • Site HU36005
      • Orosháza, Hungary, H-5900
        • Site HU36008
      • Pecs, Hungary, H-7624
        • Site HU36007
  • Ireland
      • Dublin, Ireland, 8
        • Site IE35302
      • Limerick, Ireland, V94 F858
        • Site IE35304
  • Italy
      • Firenze, Italy, 50134
        • Site IT39009
      • Genova, Italy, 16132
        • Site IT39005
      • Milano, Italy, 20122
        • Site IT39004
      • Monza, Italy, 20900
        • Site IT39003
      • Napoli, Italy, 80131
        • Site IT39007
      • Padova, Italy, 35128
        • Site IT39002
      • Pisa, Italy, 56124
        • Site IT39001
      • Roma, Italy, 00168
        • Site IT39006
      • Torino, Italy, 10154
        • Site IT39010
  • Poland
      • Gdynia, Poland, 81-348
        • Site PL48004
      • Szczecin, Poland, 71-899
        • Site PL48011
      • Warsaw, Poland, 02-507
        • Site PL48008
      • Warsaw, Poland, 02-781
        • Site PL48002
      • Zgierz, Poland, 95-100
        • Site PL48003
    • PL
      • Lodz, PL, Poland, 91-347
        • Site PL48012
  • Portugal
      • Almada, Portugal, 2800-525
        • Site PT35101
      • Amadora, Portugal, 2720-276
        • Site PT35102
      • Cotter, Portugal, 4835-044
        • Site PT35106
      • Vila Nova de Gaia, Portugal, 4434-502
        • Site PT35104
      • Vila Real, Portugal, 5000-508
        • Site PT35107
  • Romania
      • Bucharest, Romania, 21105
        • Site RO40001
      • Cluj-Napoca, Romania, 400348
        • Site RO40003
      • Lasi, Romania, 700116
        • Site RO40002
  • Russian Federation
      • Moscow, Russian Federation, 115478
        • Site RU70001
      • Moscow, Russian Federation, 123423
        • Site RU70003
  • Slovenia
      • Ljubljana, Slovenia, 1000
        • Site SI38601
      • Ljubljana, Slovenia, 1000
        • Site SI38605
      • Maribor, Slovenia, 2000
        • Site SI38602
      • Murska Sobota, Slovenia, 9000
        • Site SI38603
  • Spain
      • Barakaldo, Vizcaya, Spain, 48903
        • Site ES34003
      • Barcelona, Spain, 08035
        • Site ES34004
      • Madrid, Spain, 28040
        • Site ES34005
      • Valencia, Spain, 46026
        • Site ES34006
  • Sweden
      • Göteborg, Sweden, 41685
        • Site SE46002
      • Jönköping, Sweden, 55185
        • Site SE46004
      • Lund, Sweden, 22185
        • Site SE46001
      • Uppsala, Sweden, 75185
        • Site SE46005
  • Switzerland
      • St. Gallen, Switzerland, 9007
        • Site CH41002
      • Zürich, Switzerland, 8006
        • Site CH41004
    • Ticino
      • Lugano, Ticino, Switzerland, CH-6903
        • Site CH41001
  • Turkey
      • Adana, Turkey, 01330
        • Site TR90003
      • Ankara, Turkey, 06100
        • Site TR90002
      • Ankara, Turkey, 06100
        • Site TR90007
      • Antalya, Turkey, 07059
        • Site TR90001
      • Eskisehir, Turkey, 26480
        • Site TR90006
      • Istanbul, Turkey, 34662
        • Site TR90005
      • Istanbul, Turkey, 34890
        • Site TR90004
  • United Kingdom
      • Blackpool, United Kingdom, FY3 8NR
        • Site GB44008
      • Cardiff, United Kingdom, CF14 4XW
        • Site GB44005
      • London, United Kingdom, E1 1BB
        • Site GB44010
      • Truro, United Kingdom, TR1 3LJ
        • Site GB44009
    • Nottinghamshire
      • Sutton in Ashfield, Nottinghamshire, United Kingdom, NG17 4JL
        • Site GB44003
    • UK
      • Bristol, UK, United Kingdom, BS2 8HW
        • Site GB44006

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fidaxomicin Extended Pulsed Regimen (EPFX)
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
oral tablets administered in an extended pulsed regimen
Other Names:
  • Dificid
  • ASP2819
  • Dificlir
  • OPT-80
Experimental: Vancomycin
Participants receive 125 mg vancomycin from day 1 to day 10, 4 times daily.
Drug: Vancomycin
oral capsule
Other Names:
  • Vancocin

What is the study measuring?

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
Time Frame: 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.
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
Time Frame: 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.
Day 40, 55, 90
Percentage of Participants with a Clinical Response of CDI at 2 Days after End of Treatment
Time Frame: 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.
Day 12, 27
Percentage of Participants with a Clinical Response of CDI at Day 12
Time Frame: 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
Time Frame: 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).
Baseline through day 90
Time to Resolution of Diarrhea (TTROD)
Time Frame: 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.
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
Time Frame: 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.
Day 40, 55, 90
Time to Recurrence of CDI after End of Active Treatment
Time Frame: 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.
From day 10 up to day 90
Disease-free Survival After Day 10
Time Frame: 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.
From day 10 up to day 90

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Astellas Pharma Europe Ltd.

Collaborators

Merck Sharp & Dohme LLC

Investigators

  • Study Director: Medical Director, Astellas Pharma Europe Ltd.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 6, 2014

Primary Completion (Actual)

March 27, 2016

Study Completion (Actual)

May 5, 2016

Study Registration Dates

First Submitted

September 25, 2014

First Submitted That Met QC Criteria

September 30, 2014

First Posted (Estimated)

October 2, 2014

Study Record Updates

Last Update Posted (Actual)

October 31, 2024

Last Update Submitted That Met QC Criteria

October 29, 2024

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2819-MA-1002
  • 2013-004619-31 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as products terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Further details on Astellas' data sharing policy can be found at https://www.clinicaltrials.astellas.com/transparency/.

IPD Sharing Time Frame

Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.

IPD Sharing Access Criteria

Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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