Evaluation of Xiaflex: Trial of Effectivenss iN Dupuytren's

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Dupuytren's Disease

Intervention / Treatment
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* Drug: collagenase injection
* Procedure: limited palmar fasciectomy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: collagenase injection<br>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<br>* injection<br>* Other names: enzyme, collagenase clostridium histolyticum, xiaflex;|
| Active Comparator: limited palmar fasciectomy<br>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<br>* surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 1 year | 
| 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. | 1 year | 
| 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. | 1 year | 
| 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. | 1 year | 
| 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). | 1-4 years | 
| 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) | 1 year | 
| 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) | 1 year | 
| 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) | 1 year |