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Trial Comparing Treatment Strategies in Dupuytren's Contracture (DETECT)

Primary Purpose

Dupuytren Contracture

Status
Active
Phase
Phase 4
Locations
Finland
Study Type
Interventional
Intervention
Percutaneous needle fasciotomy (PNF)
Collagenase Clostridium Histolyticum (CCH) 2.9 MG/ML [Xiaflex]
Limited fasciectomy (LF)
Sponsored by
Tampere University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dupuytren Contracture focused on measuring Hand, Xiapex, Xiaflex, Clostridium histolyticum collagenase, Needle, Surgery, Aponeurectomy, Aponeurotomy, Fasciotomy, Fasciectomy, Dupuytren's disease, Dupuytren's contracture, Contracture, Connective tissue disease

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • patients with ≥20° passive extension deficit (PED) in metacarpophalangeal (MP) or proximal interphalangeal (PIP) joint, or TPED of ≥30° in MP and PIP joints 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
  • TPED > 135° (Tubiana stage 4) in finger to be treated
  • rheumatoid arthritis
  • previous fracture in finger to be treated, which affects range of motion of MP or PIP joint
  • age > 80 years

Sites / Locations

  • Central Hospital of Central Finland
  • Tampere University Hospital
  • Oulu University hospital
  • Kuopio University hospital
  • Helsinki University hospital
  • Turku University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Percutaneous needle fasciotomy (PNF)

Collagenase clostridium histolyticum (CCH)

Limited fasciectomy (LF)

Arm Description

PNF is a treatment in which the Dupuytren's contracture cord causing the contracture is not excised, but only divided with a hypodermic needle.

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.

In LF, the thickened part of the palmar fascia causing the contracture is excised through skin incision.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

QuickDASH
QuickDASH questionnaire is a validated upper extremity specific questionnaire consisting of 11 tasks/questions about the functional capacity and the pain.
Perceived hand function
Perceived hand function will be assessed pre- and postoperatively by VAS scale.
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.
EQ-5D-3L
EQ-5D-3L is a generic instrument for assessing quality of life comprising 5 dimensions and VAS for health level.
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.
Rate of patients achieving clinically significant improvement
Percentage of patients achieving clinically significant improvement (50% better PED) will be assessed.
Rate of patients achieving full contracture release
Percentage of patients achieving full contracture release (PED 0°-5°) will be assessed.
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?"
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.
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.
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.
Expenses
The costs are assessed by allocating previously estimated costs for interventions to each of the treatment arm.
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).
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.
Extension of the disease
Extension means that the disease will be activated in other rays than treated after the treatment.
Progression-free-survival
Progression-free-survival will be counted to each arm as mean time.
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?"
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.

Full Information

First Posted
June 8, 2017
Last Updated
March 10, 2023
Sponsor
Tampere University
Collaborators
Central Finland Hospital District, Helsinki University Central Hospital, Turku University Hospital, Tampere University Hospital, Kuopio University Hospital, Oulu University Hospital, Medcare Oy, Finnish Institute for Health and Welfare, Orton Orthopaedic Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT03192020
Brief Title
Trial Comparing Treatment Strategies in Dupuytren's Contracture
Acronym
DETECT
Official Title
DupuytrEn Treatment EffeCtiveness Trial (DETECT): Needle Fasciotomy, Surgery or Collagenase Injection for Dupuytren's Contracture
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 15, 2017 (Actual)
Primary Completion Date
May 31, 2026 (Anticipated)
Study Completion Date
May 31, 2031 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Tampere University
Collaborators
Central Finland Hospital District, Helsinki University Central Hospital, Turku University Hospital, Tampere University Hospital, Kuopio University Hospital, Oulu University Hospital, Medcare Oy, Finnish Institute for Health and Welfare, Orton Orthopaedic Hospital

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
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dupuytren Contracture
Keywords
Hand, Xiapex, Xiaflex, Clostridium histolyticum collagenase, Needle, Surgery, Aponeurectomy, Aponeurotomy, Fasciotomy, Fasciectomy, Dupuytren's disease, Dupuytren's contracture, Contracture, Connective tissue disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
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
InvestigatorOutcomes Assessor
Masking Description
Outcome assessors who measured index, middle, ring and small fingers' flexion and extension degrees were blinded. Patients had opaque gloves in their hand when visiting the blinded outcome assessor. Due to the nature of the treatments it was not possible to blind patients, leading investigators or research assistants. To minimize any bias in interpreting the findings, we blinded treatment allocation in the draft results manuscript with groups labelled as A, B and C. The writing committee reached consensus on the interpretation of the findings prior to being unblinded to group assignments.
Allocation
Randomized
Enrollment
302 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Percutaneous needle fasciotomy (PNF)
Arm Type
Experimental
Arm Description
PNF is a treatment in which the Dupuytren's contracture cord causing the contracture is not excised, but only divided with a hypodermic needle.
Arm Title
Collagenase clostridium histolyticum (CCH)
Arm Type
Experimental
Arm Description
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.
Arm Title
Limited fasciectomy (LF)
Arm Type
Active Comparator
Arm Description
In LF, the thickened part of the palmar fascia causing the contracture is excised through skin incision.
Intervention Type
Procedure
Intervention Name(s)
Percutaneous needle fasciotomy (PNF)
Other Intervention Name(s)
Percutaneous needle aponeurotomy
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Collagenase Clostridium Histolyticum (CCH) 2.9 MG/ML [Xiaflex]
Other Intervention Name(s)
[Xiapex]
Intervention Description
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.
Intervention Type
Procedure
Intervention Name(s)
Limited fasciectomy (LF)
Other Intervention Name(s)
Limited aponeurectomy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Rate of success
Description
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.
Time Frame
5 year follow-ups
Secondary Outcome Measure Information:
Title
QuickDASH
Description
QuickDASH questionnaire is a validated upper extremity specific questionnaire consisting of 11 tasks/questions about the functional capacity and the pain.
Time Frame
3 months, 2, 5 and 10 year follow-ups
Title
Perceived hand function
Description
Perceived hand function will be assessed pre- and postoperatively by VAS scale.
Time Frame
3 months, 2, 5 and 10 year follow-ups
Title
Global rating
Description
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.
Time Frame
3 months, 2, 5 and 10 year follow-ups
Title
EQ-5D-3L
Description
EQ-5D-3L is a generic instrument for assessing quality of life comprising 5 dimensions and VAS for health level.
Time Frame
3 months, 2, 5 and 10 year follow-ups
Title
Rate of Patient Accepted Symptom State
Description
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.
Time Frame
3 months, 2, 5 and 10 year follow-ups
Title
Rate of patients achieving clinically significant improvement
Description
Percentage of patients achieving clinically significant improvement (50% better PED) will be assessed.
Time Frame
10 year follow-up
Title
Rate of patients achieving full contracture release
Description
Percentage of patients achieving full contracture release (PED 0°-5°) will be assessed.
Time Frame
3 months, 2, 5 and 10 year follow-ups
Title
Willingness to undergo same treatment
Description
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?"
Time Frame
3 months and 2 year follow-ups
Title
Major adverse events
Description
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.
Time Frame
3 months, 2, 5 and 10 year follow-ups
Title
Extension deficits
Description
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.
Time Frame
3 months, 2, 5 and 10 year follow-ups
Title
Total maximum flexion
Description
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.
Time Frame
3 months, 2, 5 and 10 year follow-ups
Title
Expenses
Description
The costs are assessed by allocating previously estimated costs for interventions to each of the treatment arm.
Time Frame
2, 5 and 10 year follow-ups
Title
Progression of the disease
Description
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).
Time Frame
2, 5 and 10 year follow-ups
Title
Recurrence of the disease
Description
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.
Time Frame
2, 5 and 10 year follow-ups
Title
Extension of the disease
Description
Extension means that the disease will be activated in other rays than treated after the treatment.
Time Frame
2, 5 and 10 year follow-ups
Title
Progression-free-survival
Description
Progression-free-survival will be counted to each arm as mean time.
Time Frame
2, 5 and 10 year follow-ups
Title
Favored treatment modality questionnaire
Description
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?"
Time Frame
2, 5 and 10 year follow-ups
Title
Rate of success
Description
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.
Time Frame
3 months, 2 and 10 year follow-ups

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mikko P Räisänen, M.D.
Organizational Affiliation
Tampere University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Harry J Göransson, M.D., Ph.D., adjunct professor
Organizational Affiliation
Tampere University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Aleksi RP Reito, M.D., Ph.D., adjunct professor
Organizational Affiliation
Central Finland Central Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Hannu Kautiainen, MSc
Organizational Affiliation
Medcare Ltd
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Antti OV Malmivaara, M.D., Ph.D., adjunct professor
Organizational Affiliation
Finnish Institute for Health and Welfare
Official's Role
Principal Investigator
Facility Information:
Facility Name
Central Hospital of Central Finland
City
Jyväskylä
State/Province
Keski-Suomi
ZIP/Postal Code
40620
Country
Finland
Facility Name
Tampere University Hospital
City
Tampere
State/Province
Pirkanmaa
ZIP/Postal Code
33521
Country
Finland
Facility Name
Oulu University hospital
City
Oulu
State/Province
Pohjois-Pohjanmaa
ZIP/Postal Code
90220
Country
Finland
Facility Name
Kuopio University hospital
City
Kuopio
State/Province
Pohjois-Savo
ZIP/Postal Code
70029
Country
Finland
Facility Name
Helsinki University hospital
City
Helsinki
State/Province
Uusimaa
ZIP/Postal Code
00029
Country
Finland
Facility Name
Turku University Hospital
City
Turku
State/Province
Varsinais-Suomi
ZIP/Postal Code
20521
Country
Finland

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
All the IPD will be shared with other researchers by request.
IPD Sharing Time Frame
Data will be available after the publication and it will be available for 15 years.
IPD Sharing Access Criteria
Request.
Citations:
PubMed Identifier
29599391
Citation
Raisanen MP, Karjalainen T, Goransson H, Reito A, Kautiainen H, Malmivaara A, Leppanen OV. DupuytrEn Treatment EffeCtiveness Trial (DETECT): a protocol for prospective, randomised, controlled, outcome assessor-blinded, three-armed parallel 1:1:1, multicentre trial comparing the effectiveness and cost of collagenase clostridium histolyticum, percutaneous needle fasciotomy and limited fasciectomy as short-term and long-term treatment strategies in Dupuytren's contracture. BMJ Open. 2018 Mar 28;8(3):e019054. doi: 10.1136/bmjopen-2017-019054.
Results Reference
background
Available IPD and Supporting Information:
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
http://bmjopen.bmj.com/content/8/3/e019054
Available IPD/Information Comments
Protocol in BMJ Open access

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Trial Comparing Treatment Strategies in Dupuytren's Contracture

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