Evaluation of Xiaflex: Trial of Effectivenss iN Dupuytren's (EXTEND)

June 23, 2023 updated by: Achilleas Thoma, McMaster University

A Multi-Center, Randomized Controlled Trial Comparing The Clinical Effectiveness and Cost-Effectiveness of Collagenase Injection (Xiaflex) and Palmar Fasciectomy in the Management of Dupuytren's Disease

This is a prospective, multi-centre, pragmatic randomized controlled trial to compare both the clinical effectiveness and cost-effectiveness of collagenase injections (CI) versus limited palmar fasciectomy (LPF) to determine if collagenase is a superior treatment in terms of improved quality of life and reducing recurrence of the disease without serious complications. Since collagenase injections are costly it is also important to know if this novel intervention is cost-effective from the patient, Ministry of Health and societal perspectives.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Limited palmar fasciectomy (LPF) and collagenase injection (CI) are the most common procedures to manage symptoms of Dupuytren's Disease. This randomized controlled trial (RCT) aimed to directly compare patient outcomes 12 months following CI and LPF. Twenty-two patients with Dupuytren's Disease were randomized to either LPF or CI. The primary outcome was health state measured by the Michigan Hand Questionnaire. Secondary outcomes were health status (The Health Utility Index-3), function (The Unité Rhumatologique des Affections de la Main and The Southampton Dupuytren's Scoring Scheme), and range of motion (ROM) of treated digits. Measurements were collected at baseline and 1-, 3-, 6-, and 12-months post-procedure.

Study Type

Interventional

Enrollment (Actual)

22

Phase

  • Phase 3

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

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8N 3Z5
        • Hamilton Health Sciences
      • Hamilton, Ontario, Canada, L8N 4A6
        • St. Joseph's Healthcare / McMaster University
      • Hamilton, Ontario, Canada
        • St. Joseph's Hospital
      • London, Ontario, Canada, N6A 4V2
        • St. Joseph's Healthcare
      • Markham, Ontario, Canada, L6B 0T1
        • Markham Stouffville Hospital
      • Newmarket, Ontario, Canada, L3Y 5G8
        • 679 Davis St. Suite 209
      • Oakville, Ontario, Canada, L6J 0B2
        • Halton Healthcare Services
      • Oakville, Ontario, Canada
        • Oakville Trafalgar Hospital
      • Ottawa, Ontario, Canada, K1Y 4E9
        • The Ottawa Hospital
      • Toronto, Ontario, Canada, M2J 1V1
        • North York General Hospital

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Canadian Citizen
  2. 18 years of age or older
  3. Dupuytren's contracture of the metacarpophalangeal (MCP) joint or of the proximal interphalangeal (PIP) joint with a fixed flexion contracture of 20º or greater in at least 1 finger (not the thumb)
  4. Demonstrated inability to simultaneously place the affected finger and palm flat on a table
  5. Able to understand and communicate in English

Exclusion Criteria:

  1. Previous treatment of the primary joint within 90 days of study inclusion
  2. Patients undergoing any concomitant procedure on the same hand (e.g. carpal tunnel release, stenosing tenosynovitis release)
  3. Persistent extension deficit from a previous surgery of the same digit
  4. Any chronic muscular or neuromuscular disorder affecting wrist or hand
  5. Patient generally unfit for surgery
  6. Patient with specific treatment preference
  7. Bleeding disorder or recent stroke
  8. Allergy to collagenase
  9. Collagenase treatment or treatment with any investigational drug within 30 days of study inclusion
  10. Use of a tetracycline derivative within 14 days of first dose of study drug (because tetracycline derivatives may inhibit the collagenolytic activity of mammalian collagenase homologs [i.e., matrix metalloproteinases])
  11. Pregnant or breast feeding patients
  12. Patients who do not have insurance coverage for collagenase injections
  13. Patients who are unable to provide informed consent or are unable to complete quality of life questionnaires due to mental capacity or neuro-psychological problems.

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: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: collagenase injection
This procedure will be performed either in a minor procedure room or the hand clinic as per surgeon's routine practice. Collagenase will be administered with or without local anesthesia. As this is a pragmatic study there may be more than one digit injected at a time just as surgery occurs on more than one digit at a time. A recently published study by Gaston et al confirmed that two concurrent injections of collagenase to 2 affected joints in the same hand are generally well tolerated and the frequency of most adverse events (AEs) is similar to those reported in studies that use single sequential injections.
Drug: collagenase injection
injection
Other Names:
  • enzyme, collagenase clostridium histolyticum, xiaflex
Active Comparator: limited palmar fasciectomy
The Dupuytren's cord will be excised under local anesthesia in a minor procedure room setting or main operating room under local or general anesthetic depending on the complexity of the disease and the surgeon's routine. As this is a pragmatic study comparison of collagenase injections (novel intervention) to limited palmar fasciectomy as it is actually presently performed in all settings academic or community (local in minor room or general/local anesthetic in the main operating room) will be examined. Surgery will be performed according to the operating surgeon's preferred technique i.e. zig-zag Brunner incision or straight incision with z-plasty closure of the skin.
Procedure: limited palmar fasciectomy
surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Health-related Quality of Life (HRQL) Using the Michigan Hand Outcomes Questionnaire (MHQ)
Time Frame: 1 year
Michigan Hand Outcomes Questionnaire (MHQ). Converted to a score rated 0-100 (where higher scores represent better function).
1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
HRQL Measured With the Health Utility Index Mark 3 (HUI3) of Health
Time Frame: 1 year
Health Utility Index Mark 3 (HUI3) of Health. The HUI3 is a generic multi-attribute health-status classification instrument composed of eight attributes or dimensions: vision, hearing, speech, ambulation, dexterity, emotion, cognition, and pain with five or six levels per attribute. Dimensions are combined to produce one health utility score. The HUI3 produces health utilities anchored at 0 (minimum) for equal to being dead and 1 (maximum) for perfect health.
1 year
HRQL Measured With the Unité Rhumatologique Des Affections de la Main (URAM)
Time Frame: 1 year
Unité Rhumatologique des Affections de la Main (URAM). The URAM is a disease-specific HRQL measure developed for Dupuytren's Disease (DD) and is composed of a 9-item patient-reported questionnaire. Each item is scored between 0 and 5 depending on the difficulty in performing that particular function with total scores for DD-associated disability ranging from 0 (best) to 45 (worst). High scores suggest high levels of disability and disturbance. The URAM scale is a 1-domain outcome measure postulated to be related to disability associated with DD.
1 year
HRQL Measured With the Southampton Dupuytren's Scoring Scheme (SDSS)
Time Frame: 1 year
The SDSS is disease-specific scoring system developed for Dupuytren's Disease (DD) with 5 domains, each relevant to DD and scored on a five-point scale (no problem, mild inconvenience, modest inconvenience, definitely troublesome, severe problem). The minimum score is 0 and maximum score is 20 with higher scores suggesting higher levels of disability.
1 year
Quality Adjusted Life Years (QALY) Measured With the Health Utility Index Mark 3 (HUI3)
Time Frame: 1 year
QALY was calculated by multiplying the difference between quality of life, as measured by the HUI-3 score before and after the intervention by the remaining years of life of the average patient (i.e., life expectancy - patient's age). Life expectancy was set at 79 years for males, and 84 years for females. Higher QALYs represent improved (better) patient outcomes.
1 year
Recurrence Rates
Time Frame: 1-4 years
Reccurence was measured as whether or not participants received a repeat diagnosis of Dupuytren's disease with loss of finger extension at the site of prior intervention and underwent palmar fasciectomy (following the collagenase injection or as a revision operation) after initial study treatment. The time horizon for recurrence was between 1-4 years post initial study treatment. Outcome was dichotomous (i.e., recurrence; yes or no).
1-4 years
Loss of Extension MCP
Time Frame: 1 year
Passive range of motion degree of extension was measured using a goniometer. Difference in degree, as measured by a goniometer, between the participant's resting maximum extension of the metacarpal-phalangeal joint, relative to a metacarpal-phalangeal joint at full extension (i.e., 0 degrees)
1 year
Loss of Extension PIP
Time Frame: 1 year
Passive range of motion degree of extension was measured using a goniometer. Difference in degree, as measured by a goniometer, between the participant's resting maximum extension of the proximal inter-phalangeal joint, relative to a proximal inter-phalangeal joint at full extension (i.e., 0 degrees)
1 year
Loss of Extension DIP
Time Frame: 1 year
Passive range of motion degree of extension was measured using a goniometer. Difference in degree, as measured by a goniometer, between the participant's resting maximum extension of the distal inter-phalangeal joint, relative to a distal inter-phalangeal joint at full extension (i.e., 0 degrees)
1 year

Collaborators and Investigators

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

Sponsor

McMaster University

Collaborators

The Physicians' Services Incorporated Foundation

Investigators

  • Principal Investigator: Achilleas Thoma, MD MSc FRCSC, McMaster University

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)

July 8, 2017

Primary Completion (Actual)

December 17, 2021

Study Completion (Actual)

December 17, 2021

Study Registration Dates

First Submitted

March 22, 2016

First Submitted That Met QC Criteria

March 29, 2016

First Posted (Estimated)

April 1, 2016

Study Record Updates

Last Update Posted (Actual)

July 18, 2023

Last Update Submitted That Met QC Criteria

June 23, 2023

Last Verified

June 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PSI 2016-03

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

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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