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

Primary Purpose

Dupuytren's Disease

Status
Completed
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
collagenase injection
limited palmar fasciectomy
Sponsored by
McMaster University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dupuytren's Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Hamilton Health Sciences
  • St. Joseph's Healthcare / McMaster University
  • St. Joseph's Hospital
  • St. Joseph's Healthcare
  • Markham Stouffville Hospital
  • 679 Davis St. Suite 209
  • Halton Healthcare Services
  • Oakville Trafalgar Hospital
  • The Ottawa Hospital
  • North York General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

collagenase injection

limited palmar fasciectomy

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Health-related Quality of Life (HRQL) Using the Michigan Hand Outcomes Questionnaire (MHQ)
Michigan Hand Outcomes Questionnaire (MHQ). Converted to a score rated 0-100 (where higher scores represent better function).

Secondary Outcome Measures

HRQL Measured With the Health Utility Index Mark 3 (HUI3) of Health
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.
HRQL Measured With the Unité Rhumatologique Des Affections de la Main (URAM)
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.
HRQL Measured With the Southampton Dupuytren's Scoring Scheme (SDSS)
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.
Quality Adjusted Life Years (QALY) Measured With the Health Utility Index Mark 3 (HUI3)
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.
Recurrence Rates
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).
Loss of Extension MCP
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)
Loss of Extension PIP
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)
Loss of Extension DIP
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)

Full Information

First Posted
March 22, 2016
Last Updated
June 23, 2023
Sponsor
McMaster University
Collaborators
The Physicians' Services Incorporated Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT02725528
Brief Title
Evaluation of Xiaflex: Trial of Effectivenss iN Dupuytren's
Acronym
EXTEND
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
July 8, 2017 (Actual)
Primary Completion Date
December 17, 2021 (Actual)
Study Completion Date
December 17, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
McMaster University
Collaborators
The Physicians' Services Incorporated Foundation

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dupuytren's Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
22 (Actual)

8. Arms, Groups, and Interventions

Arm Title
collagenase injection
Arm Type
Active Comparator
Arm Description
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.
Arm Title
limited palmar fasciectomy
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
collagenase injection
Other Intervention Name(s)
enzyme, collagenase clostridium histolyticum, xiaflex
Intervention Description
injection
Intervention Type
Procedure
Intervention Name(s)
limited palmar fasciectomy
Intervention Description
surgery
Primary Outcome Measure Information:
Title
Health-related Quality of Life (HRQL) Using the Michigan Hand Outcomes Questionnaire (MHQ)
Description
Michigan Hand Outcomes Questionnaire (MHQ). Converted to a score rated 0-100 (where higher scores represent better function).
Time Frame
1 year
Secondary Outcome Measure Information:
Title
HRQL Measured With the Health Utility Index Mark 3 (HUI3) of Health
Description
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.
Time Frame
1 year
Title
HRQL Measured With the Unité Rhumatologique Des Affections de la Main (URAM)
Description
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.
Time Frame
1 year
Title
HRQL Measured With the Southampton Dupuytren's Scoring Scheme (SDSS)
Description
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.
Time Frame
1 year
Title
Quality Adjusted Life Years (QALY) Measured With the Health Utility Index Mark 3 (HUI3)
Description
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.
Time Frame
1 year
Title
Recurrence Rates
Description
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).
Time Frame
1-4 years
Title
Loss of Extension MCP
Description
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)
Time Frame
1 year
Title
Loss of Extension PIP
Description
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)
Time Frame
1 year
Title
Loss of Extension DIP
Description
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)
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Canadian Citizen 18 years of age or older 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) Demonstrated inability to simultaneously place the affected finger and palm flat on a table Able to understand and communicate in English Exclusion Criteria: Previous treatment of the primary joint within 90 days of study inclusion Patients undergoing any concomitant procedure on the same hand (e.g. carpal tunnel release, stenosing tenosynovitis release) Persistent extension deficit from a previous surgery of the same digit Any chronic muscular or neuromuscular disorder affecting wrist or hand Patient generally unfit for surgery Patient with specific treatment preference Bleeding disorder or recent stroke Allergy to collagenase Collagenase treatment or treatment with any investigational drug within 30 days of study inclusion 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]) Pregnant or breast feeding patients Patients who do not have insurance coverage for collagenase injections 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Achilleas Thoma, MD MSc FRCSC
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hamilton Health Sciences
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 3Z5
Country
Canada
Facility Name
St. Joseph's Healthcare / McMaster University
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 4A6
Country
Canada
Facility Name
St. Joseph's Hospital
City
Hamilton
State/Province
Ontario
Country
Canada
Facility Name
St. Joseph's Healthcare
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 4V2
Country
Canada
Facility Name
Markham Stouffville Hospital
City
Markham
State/Province
Ontario
ZIP/Postal Code
L6B 0T1
Country
Canada
Facility Name
679 Davis St. Suite 209
City
Newmarket
State/Province
Ontario
ZIP/Postal Code
L3Y 5G8
Country
Canada
Facility Name
Halton Healthcare Services
City
Oakville
State/Province
Ontario
ZIP/Postal Code
L6J 0B2
Country
Canada
Facility Name
Oakville Trafalgar Hospital
City
Oakville
State/Province
Ontario
Country
Canada
Facility Name
The Ottawa Hospital
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Y 4E9
Country
Canada
Facility Name
North York General Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M2J 1V1
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Evaluation of Xiaflex: Trial of Effectivenss iN Dupuytren's

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