Dupuytren's Disease
Conditions
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.
Interventions
injection
PROCEDURElimited palmar fasciectomy
surgery
Sponsors
The Physicians' Services Incorporated Foundation
McMaster University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Health-related Quality of Life (HRQL) Using the Michigan Hand Outcomes Questionnaire (MHQ) | 1 year | Michigan Hand Outcomes Questionnaire (MHQ). Converted to a score rated 0-100 (where higher scores represent better function). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HRQL Measured With the Unité Rhumatologique Des Affections de la Main (URAM) | 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. |
| HRQL Measured With the Southampton Dupuytren's Scoring Scheme (SDSS) | 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. |
| Quality Adjusted Life Years (QALY) Measured With the Health Utility Index Mark 3 (HUI3) | 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. |
| HRQL Measured With the Health Utility Index Mark 3 (HUI3) of Health | 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. |
| Loss of Extension MCP | 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) |
| Loss of Extension PIP | 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) |
| Loss of Extension DIP | 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) |
| Recurrence Rates | 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). |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
collagenase injection: injection | 8 |
| 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.
limited palmar fasciectomy: surgery | 13 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 4 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Total | Collagenase Injection | Limited Palmar Fasciectomy |
|---|---|---|---|
| Affected Digit Little | 10 Participants | 2 Participants | 8 Participants |
| Affected Digit Little & Ring | 4 Participants | 4 Participants | 0 Participants |
| Affected Digit Little, Ring & Long | 1 Participants | 0 Participants | 1 Participants |
| Affected Digit Long | 1 Participants | 1 Participants | 0 Participants |
| Affected Digit Long & Little | 1 Participants | 0 Participants | 1 Participants |
| Affected Digit Ring | 4 Participants | 1 Participants | 3 Participants |
| Affected Hand Left | 6 Participants | 2 Participants | 4 Participants |
| Affected Hand Right | 15 Participants | 6 Participants | 9 Participants |
| Age, Continuous | 65.3 years STANDARD_DEVIATION 9.2 | 65.8 years STANDARD_DEVIATION 10.2 | 65 years STANDARD_DEVIATION 9 |
| Race and Ethnicity Not Collected | 0 Participants | — | — |
| Region of Enrollment Canada | 21 participants | 8 participants | 13 participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 18 Participants | 7 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 13 |
| other Total, other adverse events | 0 / 8 | 0 / 13 |
| serious Total, serious adverse events | 0 / 8 | 0 / 13 |
Outcome results
Primary
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).
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Collagenase Injection | Health-related Quality of Life (HRQL) Using the Michigan Hand Outcomes Questionnaire (MHQ) | 78.1 units on a scale | Standard Deviation 14.9 |
| Limited Palmar Fasciectomy | Health-related Quality of Life (HRQL) Using the Michigan Hand Outcomes Questionnaire (MHQ) | 68.3 units on a scale | Standard Deviation 15.7 |
Comparison: 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 26.0p-value: 0.05ANCOVA
Secondary
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.
Time frame: 1 year
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Collagenase Injection | HRQL Measured With the Health Utility Index Mark 3 (HUI3) of Health | 0.8 units on a scale | Standard Deviation 0.79 |
| Limited Palmar Fasciectomy | HRQL Measured With the Health Utility Index Mark 3 (HUI3) of Health | 0.79 units on a scale | Standard Deviation 0.14 |
Comparison: 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 26.0p-value: 0.05ANCOVA
Secondary
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.
Time frame: 1 year
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Collagenase Injection | HRQL Measured With the Southampton Dupuytren's Scoring Scheme (SDSS) | 6.5 units on a scale | Standard Deviation 3.2 |
| Limited Palmar Fasciectomy | HRQL Measured With the Southampton Dupuytren's Scoring Scheme (SDSS) | 7.2 units on a scale | Standard Deviation 3.7 |
Comparison: 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 26.0p-value: 0.05ANCOVA
Secondary
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.
Time frame: 1 year
Population: 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).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Collagenase Injection | HRQL Measured With the Unité Rhumatologique Des Affections de la Main (URAM) | 4.6 units on a scale | Standard Deviation 9.2 |
| Limited Palmar Fasciectomy | HRQL Measured With the Unité Rhumatologique Des Affections de la Main (URAM) | 5.2 units on a scale | Standard Deviation 7.6 |
Comparison: 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 26.0p-value: 0.05ANCOVA
Secondary
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)
Time frame: 1 year
Population: 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).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Collagenase Injection | Loss of Extension DIP | 8 Degrees | Standard Deviation 0 |
| Limited Palmar Fasciectomy | Loss of Extension DIP | 10 Degrees | Standard Deviation 14.14 |
Comparison: 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 26.0p-value: 0.05ANCOVA
Secondary
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)
Time frame: 1 year
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Collagenase Injection | Loss of Extension MCP | 20 Degrees | Standard Deviation 26.9 |
| Limited Palmar Fasciectomy | Loss of Extension MCP | 2.56 Degrees | Standard Deviation 3.97 |
Comparison: 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 26.0p-value: 0.05ANCOVA
Secondary
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)
Time frame: 1 year
Population: 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).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Collagenase Injection | Loss of Extension PIP | 23.2 Degrees | Standard Deviation 18.17 |
| Limited Palmar Fasciectomy | Loss of Extension PIP | 17.2 Degrees | Standard Deviation 21.81 |
Comparison: 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 26.0p-value: 0.05ANCOVA
Secondary
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.
Time frame: 1 year
Population: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Collagenase Injection | Quality Adjusted Life Years (QALY) Measured With the Health Utility Index Mark 3 (HUI3) | 0.83 quality-adjusted life years | Standard Deviation 1.7 |
| Limited Palmar Fasciectomy | Quality Adjusted Life Years (QALY) Measured With the Health Utility Index Mark 3 (HUI3) | 0.93 quality-adjusted life years | Standard Deviation 2.8 |
Comparison: 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 26.0p-value: 0.05ANCOVA
Secondary
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).
Time frame: 1-4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Collagenase Injection | Recurrence Rates | 3 Participants |
| Limited Palmar Fasciectomy | Recurrence Rates | 1 Participants |
Comparison: 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 26.0p-value: 0.05ANCOVA