Fasciectomy vs Collagenase Injection in Recurrent Dupuytren Disease

Surgical Fasciectomy Versus Collagenase Injection in Treating Recurrent Dupuytren Disease: a Randomized Controlled Trial

This randomized controlled trial will compare the outcome of surgery (fasciectomy) with that of local injection of Collagenase Clostridium Histolyticum in patients with recurrent finger joint contracture after previous treatment with Surgery, collagenase injection or needle fasciotomy. Half of the participants will be treated with surgery while the other half will receive collagenase injection.

Study Overview

• Status: Active, not recruiting
• Conditions: Dupuytren Disease of Finger
• Intervention / Treatment: Procedure: Fasciectomy; Drug: Collagenase Clostridium Histolyticum

Detailed Description

No definitive cure for Dupuytren disease (DD) currently exists and recurrence of finger contractures after treatment is common. Surgical fasciectomy is considered the standard treatment method for patients with recurrence. However, the procedure is associated with a high incidence of complications. Injection of Collagenase Clostridium Histolyticum into Dypuytren cords causing the contracture is a non-surgical treatment for DD and has been shown to be a safe and effective method. Most studies regarding collagenase injection have involved first-time treatment. Efficacy of collagenase injection in patients with recurrent DD, beyond the immediate effect, has not yet been determined. This randomized trial will compare the outcome of surgical fasciectomy and collagenase injection in treating patients with finger joints contracture due to recurrent DD. The study is a single-center randomized controlled trial. Patients referred to an orthopedic department are screened for eligibility. The inclusion criteria are recurrence of DD in one or more fingers after previous treatment with fasciectomy, collagenase injection or needle fasciotomy, a passive extension deficit ≥30 degrees in the metacarpophalangeal (MCP) and/or proximal interphalangeal (PIP) joint in a previously treated finger, and a palpable cord believed to cause the recurrent contracture. A total of 56 patients will be randomized (computer-generated randomization list, stratified according to type of previous treatment and affected finger), to either surgical fasciectomy or collagenase injection. A blinded hand therapist will measure range of motion (including active and passive extension deficit) at baseline and 3 months, 12 months, 24 months and 60 months after treatment. The primary outcomes are the total active extension deficit (MCP plus PIP) at 3 months and the proportion of patients with contracture worsening ≥20 degrees in the treated finger joint at 2 years compared to 3 months. The secondary outcomes include total passive extension deficit, the 11-item disabilities of the arm, shoulder and hand (QuickDASH) score, EuroQol 5-dimensions (EQ-5D) index, cold intolerance symptom severity score, palmar pain score, pain visual analog scale (VAS) score, satisfaction VAS score, adverse events and costs.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• Sweden
  • Hässleholm, Sweden, SE 28125
    • Department of Orthopedics Hässleholm-Kristianstad

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Seeking treatment for recurrence of Dupuytren´s contracture in at least one finger.
• Passive extension deficit of 30 degrees or greater in the metacarpophalangeal and/or proximal interphalangeal joint in a finger previously treated with surgical fasciectomy, collagenase injections, or needle fasciotomy.
• Palpable cord in the palm and/or affected finger causing the recurrent contracture.
• No Surgery, collagenase injection or needle fasciotomy in the finger with recurrent contracture in the past 12 months.

Exclusion Criteria:

• Medical comorbidities that constitute a contraindication for surgical fasciectomy or collagenase injection.
• Signs of nerve or vascular injury in the affected finger.
• Osteoarthritis in the metacarpophalangeal and/or proximal interphalangeal joint joint in the affected finger
• Complications after the previous treatment, such as infection or complex regional pain syndrome (CRPS).
• Previous trauma or other surgery involving the affected finger.
• More than 2 previous surgeries, collagenase injections or needle fasciotomies in the affected finger.
• Examining surgeon deems further fasciectomy inappropriate or potentially associated with very high complication risk, for example in severe contracture and/or severe scarring after the previous surgeries and considers salvage procedures (such as amputation) as the more appropriate treatment.
• Patient refusal to participate

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Surgical fasciectomy; Fasciectomy according to usual care (surgery), implying excision of Dupuytren's cords and tissues to release the finger joint contractures	Procedure: Fasciectomy; Surgical excision of Dupuytren cords causing finger joint contractures. Surgery done under regional or general anesthesia. Additional procedures (such as capsulotomy or skin graft) done if surgeon deemed necessary.; Other Names: Surgery
Experimental: Collagenase Clostridium Histolyticum; Injection of 0.8 mg collagenase clostridium histolyticum into multiple spots in the Dupuytren cords followed by finger manipulation 1-2 days later to release the finger joint contractures	Drug: Collagenase Clostridium Histolyticum; Injection of Collagenase into the Dupuytren cord after local anesthesia (nerve block) followed 24-48 hours later by finger manipulation after local anesthesia; Other Names: Non-surgical treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total active extension deficit (metacarpophalangeal plus proximal interphalangeal joints)	Extension deficit of the metacarpophalangeal and interphalangeal joints of the treated finger measured with hand-held goniometer (0 degrees indicates no extension deficit)	Change from baseline to 3 months
Proportion of patients with worsening in total active extension deficit ≥20 degrees	Extension deficit of the metacarpophalangeal and interphalangeal joints of the treated finger measured with hand-held goniometer (0 degrees indicates no extension deficit)	24 months compared to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
11-item disabilities of the arm, shoulder and hand (QuickDASH) score	A patient-reported outcome measure of activity limitations related to upper extremity disorders, with total score range from 0 (best) to 100 (worst)	Change over time from from baseline, 3 weeks, 6 weeks, 3 months, 12 months, 24 months and 60 months
EuroQoL 5-dimensions (EQ-5D) Index	Health-status and quality-of-life patient-reported measure, consists of 5 items, a single weighted score, the EQ-5D index, is calculated from the 5 dimensions, ranging from -0.594 (worst) to 1.0 (perfect health)	Change over time from from baseline, 3 weeks, 6 weeks, 3 months, 12 months, 24 months and 60 months
Pain score	Visual analog scale of pain in the treated hand, score range from 0 (best) to 100 (worst)	Change over time from from baseline, 3 weeks, 6 weeks, 3 months, 12 months, 24 months and 60 months
Satisfaction score	Visual analog scale of patient satisfaction with treatment outcome, score range from 0 (best) to 100 (worst)	3 weeks, 6 weeks, 3 months, 12 months, 24 months and 60 months
Adverse events	All observed and reported adverse events will be recorded on a standard form. Serious adverse events include nerve, artery or tendon damage, deep infection, complex regional pain syndrome and any complications requiring surgery or hospital admission.	Anytime during 24 months after treatment
Costs	Total treatment cost, direct (medications, surgery, materials, visits etc) and indirect (sick leave related to the treatment)	From baseline through 24 months
Total active motion	Sum of active range of motion of metacarpophalangeal, proximal intephalangeal and distal interphalangeal joints of the treated finger	Change from baseline to 3 months, 12 months, 24 months and 60 months
Total active extension deficit (metacarpophalangeal plus proximal interphalangeal joints)	Active extension deficit of the metacarpophalangeal and interphalangeal joints of the treated finger measured with hand-held goniometer (0 degrees indicates no extension deficit)	Change from baseline to 12 months, 24 months and 60 months
Proportion of patients with worsening in total active extension deficit ≥20 degrees	Extension deficit of the metacarpophalangeal and interphalangeal joints of the treated finger measured with hand-held goniometer (0 degrees indicates no extension deficit)	60 months compared to 3 months
Palmar pain score	2-item scale inquiring about pain in the palm and related activity limitations, total score range 0 (best) to 100 (worst)	Change over time from baseline to 3 weeks, 6 weeks, 3 months, 12 months, 24 months and 60 months.
Cold intolerance symptom severity score	6-item scale inquiring about symptoms of cold intolerance, total score range 4 (best) to 100 (worst)	Change from baseline to 3 weeks, 6 weeks, 3 months, 12 months, 24 months and 60 months.
Total passive extension deficit (metacarpophalangeal plus proximal interphalangeal joints)	Passive extension deficit of the metacarpophalangeal and interphalangeal joints of the treated finger measured with hand-held goniometer (0 degrees indicates no extension deficit)	Change from baseline to 24 months and 60 months

Collaborators and Investigators

• Sponsor: Region Skane
• Investigators: Principal Investigator: Isam Atroshi, MD, PhD, Lund University

Publications and helpful links

General Publications

• Nordenskjold J, Lauritzson A, Walden M, Kopylov P, Atroshi I. Surgical fasciectomy versus collagenase injection in treating recurrent Dupuytren disease: study protocol of a randomised controlled trial. BMJ Open. 2019 Feb 25;9(2):e024424. doi: 10.1136/bmjopen-2018-024424.

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2018
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: January 14, 2018
• First Submitted That Met QC Criteria: January 14, 2018
• First Posted (Actual): January 23, 2018

Study Record Updates

• Last Update Posted (Estimated): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 7, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Musculoskeletal Diseases; Connective Tissue Diseases; Muscular Diseases; Neoplasms, Connective Tissue; Neoplasms, Fibrous Tissue; Fibroma; Contracture; Dupuytren Contracture
• Other Study ID Numbers: Hlm_DC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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