Trial Comparing Treatment Strategies in Dupuytren's Contracture

Study Overview
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Brief Summary
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Trial is a prospective, randomized, controlled, outcome assessor-blinded, three armed parallel 1:1:1, multicenter trial. The research objective is to determine, which treatment strategy 1) primary percutaneous needle fasciotomy (PNF) followed by surgical limited fasciectomy (LF) in patients who do not respond to PNF, 2) primary collagenase clostridium histolyticym (CCH) followed by LF in patients who do not respond to CCH or 3) LF as the primary (and secondary) treatment modality is the most cost-effective in treating Dupuytren´s contracture. Short- and long-term results will be published.

Detailed Description
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Dupuytren's contracture (DC) is a fibroproliferative disorder of the palmar fascia, which in time leads to flexion contracture in one or more fingers. Etiology of the disease is still unknown, but it strongly seems that genetic factors play a major role. DC is associated most commonly with Caucasian population groups from Northern Europe. The estimated global prevalence among whites is 3% to 6% and increases with age. Men women ratio is 7:1. There is no definitive cure for DC. The treatment aims at relieving the symptoms by releasing the contracture by percutaneous or operative techniques. The investigators planned a prospective, randomized, controlled, outcome assessor-blinded, three armed parallel 1:1:1, multicenter trial comparing the cost-effectiveness of 1) collagenase clostridium histolyticum followed by limited fasciectomy in non-responsive cases, 2) percutaneous needle fasciotomy followed by limited fasciectomy in non-responsive cases and 3) primary limited fasciectomy in short- and long-term follow-up in DC. Protocol is approved by Tampere university hospital institutional review board and Finnish Medicine Agency (Fimea). All patients will give written informed consent. The results of the trial will be disseminated as published articles in peer-reviewed journals. Treatment of Duputren's contracture aims at reducing the functional deficit caused by the contracture. Recurrence is almost inevitable if the follow-up is long enough. Therefore, the investigators aim to analyze the effectiveness of three different treatment strategies in long-term follow-up, in addition to short-term follow-up, which include multiple interventions rather than just single intervention. The investigators chose a pragmatic primary outcome, which comprises both objective and subjective standpoint and reflects the needs of the patients as well as goals of the healthcare system. Furthermore, our short-term results give good high quality level evidence of effectiveness of all the three treatments and long-term follow-up a good perspective to the cost-effectiveness of the strategies.

Official Title
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DupuytrEn Treatment EffeCtiveness Trial (DETECT): Needle Fasciotomy, Surgery or Collagenase Injection for Dupuytren's Contracture

Conditions
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Dupuytren Contracture

Intervention / Treatment
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* Procedure: Percutaneous needle fasciotomy (PNF)
* Drug: Collagenase Clostridium Histolyticum (CCH) 2.9 MG/ML [Xiaflex]
* Procedure: Limited fasciectomy (LF)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients with ≥20° passive extension deficit in metacarpophalangeal (MPJ) or proximal interphalangeal joint (PIPJ), or TPED ≥30° in MPJ and PIPJ of finger/fingers II-V age > 18 years palpable cord provision of informed consent ability to fill the Finnish versions of questionnaires. Exclusion Criteria: recurrent contracture in the finger to be treated neurologic condition causing the loss of function of the finger to be treated contraindication for collagenase clostridium histolyticym (Xiapex/Xiaflex ®) pregnant or breast feeding total passive extension deficit > 135° (Tubiana stage 4) in finger to be treated rheumatoid arthritis previous fracture in finger to be treated, which affects range of motion of MPJ or PIPJ age > 80 years

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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
Interventional Model Description: This is a multicenter, randomized, outcome assessor blinded, three parallel armed (1:1:1), superiority trial comparing needle fasciotomy, collagenase injection and surgery as primary intervention for people with treatment-naïve Dupuytren's contracture with a five-year follow-up.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Limited fasciectomy (LF)<br>In LF, the thickened part of the palmar fascia causing the contracture is excised through skin incision. | Procedure: Limited fasciectomy (LF)<br>* LF is performed in general or regional anesthesia in operating room. Constricting cords will be excised under direct vision. LF has been the dominant technique of surgical treatment. If patient seeks for a treatment the recurrence of the disease will be treated with LF as long as needed.<br>* Other names: Limited aponeurectomy;|
| Experimental: Percutaneous needle fasciotomy (PNF)<br>PNF is a treatment in which the Dupuytren's contracture cord causing the contracture is not excised, but only divided with a hypodermic needle. | Procedure: Percutaneous needle fasciotomy (PNF)<br>* The division of the cord can be made under local anesthesia in the clinic and takes only a few minutes to perform. It can be performed whenever the cord is palpable. There are only puncture wounds left, and hence, the patient can start normal use of the hand the day after the procedure. If patient seeks for a treatment and the recurrence of the disease can not be treated by the PNF or patient is not willing to new PNF patient will be treated with LF.<br>* Other names: Percutaneous needle aponeurotomy;Procedure: Limited fasciectomy (LF)<br>* LF is performed in general or regional anesthesia in operating room. Constricting cords will be excised under direct vision. LF has been the dominant technique of surgical treatment. If patient seeks for a treatment the recurrence of the disease will be treated with LF as long as needed.<br>* Other names: Limited aponeurectomy;|
| Experimental: Collagenase clostridium histolyticum (CCH)<br>Generic name of the drug is collagenase clostridium histolyticum. Dosage form is injectable powder, dosage 0.58 mg and frequency is one injection in four weeks up to three times. One injection is performed normally at least to three different places in the cord. | Drug: Collagenase Clostridium Histolyticum (CCH) 2.9 MG/ML [Xiaflex]<br>* CCH chemically dissolves type I collagen of which the cord is composed of. It is injected inside the cord at least three different places in the outpatient clinic and the cord can be ruptured by gently force after one to three days. If patient seeks for a treatment and the recurrence of the disease can not be treated by the CCH or patient is not willing to new CCH patient will be treated with LF.<br>* Other names: [Xiapex];Procedure: Limited fasciectomy (LF)<br>* LF is performed in general or regional anesthesia in operating room. Constricting cords will be excised under direct vision. LF has been the dominant technique of surgical treatment. If patient seeks for a treatment the recurrence of the disease will be treated with LF as long as needed.<br>* Other names: Limited aponeurectomy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of success | Success is a composite outcome comprising of 1) at least 50% contracture release from the recruitment and 2) patient is in patient accepted symptom state (PASS). PASS is defined by question: Would you be satisfied and not in need for any other treatment if the functional impairment caused by the contracture would remain the same as it is today for the rest of your life?. Primary time point is five years' follow-up visit. | 5 year follow-ups | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| QuickDASH | QuickDASH questionnaire is a validated upper extremity specific questionnaire consisting of 11 tasks/questions about the functional capacity and the pain. | 3 months, 2, 5 and 10 year follow-ups | 
| Perceived hand function | Perceived hand function will be assessed pre- and postoperatively by VAS scale. | 3 months, 2, 5 and 10 year follow-ups | 
| Global rating | Global rating to treatment effect will be evaluated by question: How would you rate the function of your hand compared to the situation before the treatment?. The options are in 5-step Likert scale from (-2) Much worse to (+2) Much better: This question is also used as anchor question in the MCII analysis in which +1 and +2 are considered to present meaningful improvement to the patient. | 3 months, 2, 5 and 10 year follow-ups | 
| EQ-5D-3L | EQ-5D-3L is a generic instrument for assessing quality of life comprising 5 dimensions and VAS for health level. | 3 months, 2, 5 and 10 year follow-ups | 
| Rate of Patient Accepted Symptom State | PASS is a relevant patient-centered outcome measurement, which reflects the overall state in which patients consider themselves as being well. It is a state of the symptoms between complete remission and subjective dissatisfaction with the symptoms. | 3 months, 2, 5 and 10 year follow-ups | 
| Rate of patients achieving clinically significant improvement | Percentage of patients achieving clinically significant improvement (50% better PED) will be assessed. | 10 year follow-up | 
| Rate of patients achieving full contracture release | Percentage of patients achieving full contracture release (PED 0°-5°) will be assessed. | 3 months, 2, 5 and 10 year follow-ups | 
| Willingness to undergo same treatment | Patient satisfaction with the treatment will be assessed by a simple yes or no question: Would you prefer the same treatment again, if the result would be the same as it is now? | 3 months and 2 year follow-ups | 
| Major adverse events | In the trial will be reported major adverse events, which include: tendon rupture, nerve injury, arterial injury, CRPS and infection, skin rupture or hematoma that needs hospitalization/revision surgery. | 3 months, 2, 5 and 10 year follow-ups | 
| Extension deficits | The total passive extension deficit (TPED) and passive extension deficit (PED) of metacarpophalangeal (MPJ) and proximal interphalangeal (PIPJ) joints are used in almost all of the DC studies. Most of the studies used the PED as their primary outcome. In this trial, the TPED and PED of MPJ and PIPJ are used as secondary outcomes. | 3 months, 2, 5 and 10 year follow-ups | 
| Total maximum flexion | Patients are seeking help for their extension deficit in DC but in the end flexion of the fingers is more important for the hand function. Our treatments should not jeopardize finger flexion in an effort to reduce the extension deficit. | 3 months, 2, 5 and 10 year follow-ups | 
| Expenses | The costs are assessed by allocating previously estimated costs for interventions to each of the treatment arm. | 2, 5 and 10 year follow-ups | 
| Progression of the disease | Recurrence or extension is treated if the patient contacts the study center and requires new treatment (ie, patient is not in the PASS anymore) and at least 20° flexion contracture is observed in one of the joints. Progression of disease is measured and reported in three levels: (1) rate of reinterventions in the arm due to recurrence or extension of the disease (clinically relevant progression); (2) costs of reinterventions (impact of progression); and (3) change in TPED in those patients who do not require further treatments (clinically irrelevant progression). | 2, 5 and 10 year follow-ups | 
| Recurrence of the disease | In this study recurrence is defined when patient considers not being in PASS anymore and seeks for further treatment, and has at least 20° contracture. | 2, 5 and 10 year follow-ups | 
| Extension of the disease | Extension means that the disease will be activated in other rays than treated after the treatment. | 2, 5 and 10 year follow-ups | 
| Progression-free-survival | Progression-free-survival will be counted to each arm as mean time. | 2, 5 and 10 year follow-ups | 
| Favored treatment modality questionnaire | Favored treatment modality will be asked from patients who undergo several treatment modalities (i.e. LF after CCH or PNF). Outcome will be assessed by question: If you presented with a contracture for the first time now, would you prefer needle fasciotomy/injectable drug as the primary treatment or would prefer having surgery at first place? | 2, 5 and 10 year follow-ups | 
| Rate of success | Success is a composite outcome comprising of 1) at least 50% contracture release from the recruitment and 2) patient is in patient accepted symptom state (PASS). PASS is defined by question: Would you be satisfied and not in need for any other treatment if the functional impairment caused by the contracture would remain the same as it is today for the rest of your life?. Primary time point is five years' follow-up visit. | 3 months, 2 and 10 year follow-ups | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hand, Xiapex, Xiaflex, Clostridium histolyticum collagenase, Needle, Surgery, Aponeurectomy, Aponeurotomy, Fasciotomy, Fasciectomy, Dupuytren's disease, Dupuytren's contracture, Contracture, Connective tissue disease