Musculoskeletal Diseases

All Conditions

Neoplasms

Skin and Connective Tissue Diseases

Nervous System Diseases

Contracture

Dupuytren Contracture

Fibroma

Neoplasms, Fibrous Tissue

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Muscular Diseases

Connective Tissue Diseases

Central Nervous System Depressants

All Drugs and Chemicals

Anesthetics

Anesthetics, Local

Anesthetics, General

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.

collagenase injection

limited palmar fasciectomy

Achilleas Thoma, MD MSc FRCSC

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.

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.

Evaluation of Xiaflex: Trial of Effectivenss iN Dupuytren's

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

Michigan Hand Outcomes Questionnaire (MHQ). Converted to a score rated 0-100 (where higher scores represent better function).

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.

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.

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.

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.

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).

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)

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)

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)

The Physicians' Services Incorporated Foundation

McMaster University

Dr. Achllieas Thoma

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.

collagenase injection: injection

Collagenase Injection

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.

limited palmar fasciectomy: surgery

Limited Palmar Fasciectomy

Total

Age, Continuous

Sex: Female, Male

Race and Ethnicity were not collected from any participant.

Race and Ethnicity Not Collected

Canada

Region of Enrollment

Affected Hand

Affected Digit

One participant in the limited palmar fasciectomy (LPF) group dropped out immediately after randomization, before baseline outcomes were measured, thus the size of the LPF group is 13, not 14.

Limitations include small sample size, poor recruitment (due health insurance coverage, treatment preference, and the discontinuation of Xiaflex® in Canada), and poor response rate and outcome data collection due to onset and restriction associated with COVID-19 pandemic.

Dr. Achilles Thoma

Between groups analysis for PROMs, QALYs and ROM at 12-months were determined using one-way analysis of covariance (ANCOVA). Group was entered as the independent variable, the 12-month outcome of interest was entered as the dependent variable and the baseline value for the corresponding outcome measure was entered as the covariate. Statistical significance was considered at p \< .05; all analyses were performed using SPSS® version 26.0

Health-related Quality of Life (HRQL) Using the Michigan Hand Outcomes Questionnaire (MHQ)

Missing data addressed by using available case analysis. Difference from flow chart due to participant's loss to follow up. Number of participant's in limited palmar fasciectomy group includes 1 additional participant who completed this outcome, but did not complete the primary outcome as indicated in the participant flow chart.

HRQL Measured With the Health Utility Index Mark 3 (HUI3) of Health

Missing data addressed by using available case analysis. Difference from flow chart due to incomplete data collection for this outcome (i.e. loss to follow up).

HRQL Measured With the Unité Rhumatologique Des Affections de la Main (URAM)

Missing data addressed by using available case analysis. Difference from flow chart due to incomplete data collection for this outcome (i.e. loss to follow up). Number of participant's in limited palmar fasciectomy group includes 1 additional participant who completed this outcome, but did not complete the primary outcome as indicated in the participant flow chart.

HRQL Measured With the Southampton Dupuytren's Scoring Scheme (SDSS)

Quality Adjusted Life Years (QALY) Measured With the Health Utility Index Mark 3 (HUI3)

Recurrence Rates

Loss of Extension MCP

Loss of Extension PIP

Loss of Extension DIP

This procedure was 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 was a pragmatic study, if injection was required in more than one digit, this was done, as per standard of care.

The patient's affected hand was prepped with antiseptic solution. Using a hubless syringe with 0.01 mL graduations and a permanently fixed 26- or 27-gauge ½ inch needle the required amount of reconstituted collagenase clostridium histolyticum was withdrawn as follows:

1. Cord affecting an MP joint, withdraw 0.25 mL of the reconstituted solution;
2. Cord affecting a PIP joint: withdraw 0.20 mL of the reconstituted solution per published guidelines.

collagenase injection: injection

The Dupuytren's cord was excised 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. The procedure was performed according to the surgeon's preferred technique (i.e., zig-zag Brunner incision or straight incision with z-plasty closure of the skin). Loupe magnification was used in surgery to identify and protect the digital neurovascular bundles. The diseased Dupuytren's fascia (cords) causing the contracture was excised. Contracted ligaments at the PIP joints were released by passive stretching or with knife intraoperatively. A plaster splint was applied at the discretion of the surgeon.

limited palmar fasciectomy: surgery

Spots Global Cancer Trial Database for Evaluation of Xiaflex: Trial of Effectivenss iN Dupuytren's

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