Evaluation of Xiaflex: Trial of Effectivenss iN Dupuytren's

NCT02725528 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: PSI 2016-03
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 10

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.

Conditions

Dupuytren's Disease

Outcome Measures

Primary Outcomes (1)

• 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).

  1 year

Secondary Outcomes (8)

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

  1 year

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

  1 year

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

  1 year

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

  1 year

• Recurrence Rates

  1-4 years

Study Arms (2)

collagenase injection

ACTIVE COMPARATOR

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.

Drug: collagenase injection

limited palmar fasciectomy

ACTIVE COMPARATOR

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.

Procedure: limited palmar fasciectomy

Interventions

collagenase injection DRUG

injection

Also known as: enzyme, collagenase clostridium histolyticum, xiaflex

collagenase injection

limited palmar fasciectomy PROCEDURE

surgery

limited palmar fasciectomy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Canadian Citizen
• years of age or older
• 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)
• Demonstrated inability to simultaneously place the affected finger and palm flat on a table
• Able to understand and communicate in English

You may not qualify if:

• Patients undergoing any concomitant procedure on the same hand (e.g. carpal tunnel release, stenosing tenosynovitis release)
• Persistent extension deficit from a previous surgery of the same digit
• Any chronic muscular or neuromuscular disorder affecting wrist or hand
• Patient generally unfit for surgery
• Patient with specific treatment preference
• Bleeding disorder or recent stroke
• Allergy to collagenase
• 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 \[i.e., matrix metalloproteinases\])
• Pregnant or breast feeding patients
• Patients who do not have insurance coverage for collagenase injections
• 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.

Sponsors & Collaborators

• McMaster University: lead
• The Physicians' Services Incorporated Foundation: collaborator

Study Sites (10)

Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

Location

St. Joseph's Healthcare / McMaster University

Hamilton, Ontario, L8N 4A6, Canada

Location

St. Joseph's Hospital

Hamilton, Ontario, Canada

Location

St. Joseph's Healthcare

London, Ontario, N6A 4V2, Canada

Location

Markham Stouffville Hospital

Markham, Ontario, L6B 0T1, Canada

Location

679 Davis St. Suite 209

Newmarket, Ontario, L3Y 5G8, Canada

Location

Halton Healthcare Services

Oakville, Ontario, L6J 0B2, Canada

Location

Oakville Trafalgar Hospital

Oakville, Ontario, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1Y 4E9, Canada

Location

North York General Hospital

Toronto, Ontario, M2J 1V1, Canada

Location

MeSH Terms

Conditions

Dupuytren Contracture

Interventions

Collagenases; Enzymes; Microbial Collagenase

Condition Hierarchy (Ancestors)

Fibroma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Contracture; Muscular Diseases; Musculoskeletal Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes and Coenzymes; Metalloproteases

Limitations and Caveats

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.

Results Point of Contact

• Title: Dr. Achilles Thoma
• Organization: McMaster University

athoma@mcmaster.ca

905-523-0019

Study Officials

• Achilleas Thoma, MD MSc FRCSC

  McMaster University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Achllieas Thoma

Study Record Dates

• First Submitted: March 22, 2016
• First Posted: April 1, 2016
• Study Start: July 8, 2017
• Primary Completion: December 17, 2021
• Study Completion: December 17, 2021
• Last Updated: July 18, 2023
• Results First Posted: July 18, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (10)