Dupuytren's interventions surgery vs collagenase
| ISRCTN | ISRCTN18254597 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN18254597 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | 2016-004251-76 |
| Protocol serial number | Sponsor ID: 2087230; HTA 15/102/04 |
| Sponsor | University Hospitals of Leicester NHS Trust |
| Funder | Health Technology Assessment Programme |
- Submission date
- 04/04/2017
- Registration date
- 11/04/2017
- Last edited
- 06/11/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Musculoskeletal Diseases
Plain English summary of protocol
Current plain English summary as of 18/11/2020:
Background and study aims
Dupuytren’s contracture is a common problem affecting the hand. The condition is caused by fibrous tissue which forces the finger to bend down into the palm meaning patients cannot straighten their finger. The common treatment is surgery to remove the tissue and straighten the bent finger. A new treatment is a Collagenase injection, which softens the fibrous tissue. This is given in clinic, and is followed up in clinic a few days later where the finger is moved to help to straighten it. Both treatments have been offered on the NHS in England and in the USA and Europe, but it is not known if the injection is as good as surgery at correcting the bent finger, if the correction continues in the long term and if the complication rates are similar. The aim of this study is to find out whether collagenase injections are as good and as safe as surgery for treating this condition and to find out the cost of both treatments to see which is the best value for money. Participants are also asked what they think about the different treatments, to see if they prefer one treatment more than the other.
Who can participate?
Patients aged 18 and over who have Dupytren’s contracture
What does the study involve?
The participant’s hand is assessed and a photograph is taken, and the participant is asked some questions about their condition and their general health. Participants are then randomly allocated to receive either the injection or surgery. Before they receive their treatment, the hand is re-assessed and the participant completes a short questionnaire about their hand health. During the study participants will complete a further 4 visits (face to face in the hospital, via video call or via telephone call) where their hand is assessed, they are asked some questions about their hand function and general health, and a photograph is taken of their hand.
What are the possible benefits and risks of participating?
The information from this study may help doctors to treat people with Dupuytren’s contracture more effectively in the future. However, as with any treatment, there are always potential risks. Common side effects of Collagenase include injection site swelling, bruising and pain. These often subside within 1 – 2 weeks of the injection. The injection may also cause dizziness, headaches, a tingling sensation or a reduced sense of touch. Very rarely, allergic reactions and tendon rupture may occur. Common side effects of surgery may be experienced such as pain, bruising, swelling or infection, in addition to anaesthetic side effects such as dizziness, headaches and numbness.
Where is the study run from?
York Trials Unit, University of York (UK). The Chief Investigator is Professor Joe Dias (https://www2.le.ac.uk/colleges/medbiopsych/teaching/academic-champions/people/professor-joseph-dias)
When is the study starting and how long is it expected to run for?
May 2017 to July 2022
Who is funding the study?
National Institute for Health Research Health Technology Assessment Programme (UK)
Who is the main contact?
1. Catherine Arundel (public)
catherine.arundel@york.ac.uk
2. Puvan Tharmanathan (scientific)
puvan.nathan@york.ac.uk
_____
Previous plain English summary as of 31/10/2018:
Background and study aims
Dupuytren’s contracture is a common problem affecting the hand. The condition is caused by fibrous tissue which forces the finger to bend down into the palm meaning patients cannot straighten their finger. The common treatment is surgery to remove the tissue and straighten the bent finger. A new treatment is a Collagenase injection, which softens the fibrous tissue. This is given in clinic, and is followed up in clinic a few days later where the finger is moved to help to straighten it. Both treatments are offered on the NHS in England and are used in the USA and Europe, but it is not known if the injection is as good as surgery at correcting the bent finger, if the correction continues in the long term and if the complication rates are similar. The aim of this study is to find out whether collagenase injections are as good and as safe as surgery for treating this condition and to find out the cost of both treatments to see which is the best value for money. Participants are also asked what they think about the different treatments, to see if they prefer one treatment more than the other.
Who can participate?
Patients aged 18 and over who have Dupytren’s contracture
What does the study involve?
The participant’s hand is assessed and a photograph is taken, and the participant is asked some questions about their condition and their general health. Participants are then randomly allocated to receive either the injection or surgery. Before they receive their treatment, the hand is re-assessed and the participant completes a short questionnaire about their hand health. During the study participants come to the hospital for another 4 visits where their hand is assessed, they are asked some questions about their hand function and general health, and a photograph of their hand is taken.
What are the possible benefits and risks of participating?
The information from this study may help doctors to treat people with Dupuytren’s contracture more effectively in the future. However, as with any treatment, there are always potential risks. Common side effects of Collagenase include injection site swelling, bruising and pain. These often subside within 1 – 2 weeks of the injection. The injection may also cause dizziness, headaches, a tingling sensation or a reduced sense of touch. Very rarely, allergic reactions and tendon rupture may occur. Common side effects of surgery may be experienced such as pain, bruising, swelling or infection, in addition to anaesthetic side effects such as dizziness, headaches and numbness.
Where is the study run from?
York Trials Unit, University of York (UK). The Chief Investigator is Professor Joe Dias (https://www2.le.ac.uk/colleges/medbiopsych/teaching/academic-champions/people/professor-joseph-dias)
When is the study starting and how long is it expected to run for?
May 2017 to October 2021
Who is funding the study?
National Institute for Health Research Health Technology Assessment Programme (UK)
Who is the main contact?
1. Catherine Arundel (public)
catherine.arundel@york.ac.uk
2. Puvan Tharmanathan (scientific)
puvan.nathan@york.ac.uk
_____
Previous plain English summary:
Background and study aims
Dupuytren’s contracture is a common problem affecting the hand. The condition is caused by fibrous tissue which forces the finger to bend down into the palm meaning patients cannot straighten their finger. The common treatment is surgery to remove the tissue and straighten the bent finger. A new treatment is a Collagenase injection, which softens the fibrous tissue. This is given in clinic, and is followed up in clinic a few days later where the finger is moved to help to straighten it. Both treatments are offered on the NHS in England and are used in the USA and Europe, but it is not known if the injection is as good as surgery at correcting the bent finger, if the correction continues in the long term and if the complication rates are similar. The aim of this study is to find out whether collagenase injections are as good and as safe as surgery for treating this condition and to find out the cost of both treatments to see which is the best value for money. Participants are also asked what they think about the different treatments, to see if they prefer one treatment more than the other.
Who can participate?
Patients aged 18 and over who have Dupytren’s contracture
What does the study involve?
The participant’s hand is assessed and a photograph is taken, and the participant is asked some questions about their condition and their general health. Participants are then randomly allocated to receive either the injection or surgery. Before they receive their treatment, the hand is re-assessed and the participant completes a short questionnaire about their hand health. During the study participants come to the hospital for another 4 visits where their hand is assessed, they are asked some questions about their hand function and general health, and a photograph of their hand is taken.
What are the possible benefits and risks of participating?
The information from this study may help doctors to treat people with Dupuytren’s contracture more effectively in the future. However, as with any treatment, there are always potential risks. Common side effects of Collagenase include injection site swelling, bruising and pain. These often subside within 1 – 2 weeks of the injection. The injection may also cause dizziness, headaches, a tingling sensation or a reduced sense of touch. Very rarely, allergic reactions and tendon rupture may occur. Common side effects of surgery may be experienced such as pain, bruising, swelling or infection, in addition to anaesthetic side effects such as dizziness, headaches and numbness.
Where is the study run from?
University of York (UK)
When is the study starting and how long is it expected to run for?
May 2017 to October 2021
Who is funding the study?
National Institute for Health Research Health Technology Assessment Programme (UK)
Who is the main contact?
1. Catherine Arundel (scientific)
catherine.arundel@york.ac.uk
2. Michelle Watson (public)
michelle.watson@york.ac.uk
Contact information
Scientific
York Trials Unit
Lower Ground Floor
ARRC Building
Department of Health Science
University of York
Heslington
York
YO10 5DD
United Kingdom
 ORCID ID |
0000-0003-0512-4339 |
|---|---|
| Phone | +44 1904 321 116 |
| catherine.arundel@york.ac.uk |
Public
York Trials Unit
Lower Ground Floor
ARRC Building
Department of Health Science
University of York
Heslington
York
YO10 5DD
United Kingdom
| Phone | +44 1904 321 844 |
|---|---|
| Puvan.nathan@york.ac.uk |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Multi-centre randomized controlled non-inferiority pragmatic trial |
| Secondary study design | Randomised controlled trial |
| Study type | Participant information sheet |
| Scientific title | A pragmatic multi-centre randomised controlled non-inferiority, cost effectiveness trial comparing injections of collagenase into the cord to surgical correction in the treatment of moderate Dupuytren’s contracture in adult patients |
| Study acronym | DISC |
| Study objectives | Collagenase injection is not inferior to limited fasciectomy in the correction of Dupuytren’s contracture of the hand. |
| Ethics approval(s) | Yorkshire and Humber Leeds West Research Ethics Committee, 22/05/2017, ref: 17/YH/0120 |
| Health condition(s) or problem(s) studied | Dupuytren's contracture |
| Intervention | Current interventions as of 18/11/2020: The participant's hand is assessed, a photograph is taken and they are asked some questions about their condition and their general health. Participants are randomised to either the intervention or the control group. Before they receive their treatment, their hand is re-assessed and they are asked to complete a short questionnaire about their hand health. 1. Intervention: Collagenase Clostridium histolyticum injections Depending on the cord affected 0.25ml or 0.20ml of reconstituted solution (0.58mg Collagenase Clostridium histolyticum) is injected as three aliquots: 0.25ml for cord in a metacarpophalangeal (MCP) joint, 0.20ml for cord in a proximal interphalangeal (PIP) joint. The three aliquots are distributed via injection into an affected cord at set anatomical points through a single needle puncture at a single time point. Patients will be scheduled for Collagenase injection within 18 weeks following randomisation (as per referral to treatment time RTT), however where possible sites should complete this procedure within 12 weeks post randomisation. After an interval of one to seven days, the patient then returns to clinic and, under local anaesthetic, the cord is snapped using a four-step process. Two additional visits by the patient may therefore be required for the intervention to be delivered; one for injection and one for manipulation. Separate cords may be injected at the same treatment, in line with the SmPC, following the injection procedure and using separate vials for each cord. If multiple cords are injected, only the reference cord injection will be deemed to be part of the trial treatment. Given the pragmatic nature of DISC, follow-up Collagenase injections will be at clinician discretion this includes the timing of manipulation and of further injections to the same cord. 2. Control: limited fasciectomy surgery Limited fasciectomy involves the removal, under anaesthesia and tourniquet control, of the diseased fascia, nodule and cord, or a part of it, to correct the contracture of the joint. As deemed clinically appropriate, the skin may then be left to heal by secondary intention, closed directly, or closed with a Z plasty or closed using a full thickness skin graft. Patients will be scheduled for the limited fasciectomy surgery to be completed within 18 weeks following randomisation (as per referral to treatment time-RTT), however where possible sites should complete this procedure within 12 weeks post randomisation. During the study participants will complete a further 4 visits (face to face in the hospital, via video call or via telephone call) where their hand is assessed, they are asked some questions about their hand function and general health, and a photograph is taken of their hand. _____ Previous interventions: The participant's hand is assessed, a photograph is taken and they are asked some questions about their condition and their general health. Participants are randomised to either the intervention or the control group. Before they receive their treatment, their hand is re-assessed and they are asked to complete a short questionnaire about their hand health. 1. Intervention: Collagenase Clostridium histolyticum injections Depending on the cord affected 0.25ml or 0.20ml of reconstituted solution (0.58mg Collagenase Clostridium histolyticum) is injected as three aliquots: 0.25ml for cord in a metacarpophalangeal (MCP) joint, 0.20ml for cord in a proximal interphalangeal (PIP) joint. The three aliquots are distributed via injection into an affected cord at set anatomical points through a single needle puncture at a single time point. Patients will be scheduled for Collagenase injection within 18 weeks following randomisation (as per referral to treatment time RTT), however where possible sites should complete this procedure within 12 weeks post randomisation. After an interval of one to seven days, the patient then returns to clinic and, under local anaesthetic, the cord is snapped using a four-step process. Two additional visits by the patient may therefore be required for the intervention to be delivered; one for injection and one for manipulation. Separate cords may be injected at the same treatment, in line with the SmPC, following the injection procedure and using separate vials for each cord. If multiple cords are injected, only the reference cord injection will be deemed to be part of the trial treatment. Given the pragmatic nature of DISC, follow-up Collagenase injections will be at clinician discretion this includes the timing of manipulation and of further injections to the same cord. 2. Control: limited fasciectomy surgery Limited fasciectomy involves the removal, under anaesthesia and tourniquet control, of the diseased fascia, nodule and cord, or a part of it, to correct the contracture of the joint. As deemed clinically appropriate, the skin may then be left to heal by secondary intention, closed directly, or closed with a Z plasty or closed using a full thickness skin graft. Patients will be scheduled for the limited fasciectomy surgery to be completed within 18 weeks following randomisation (as per referral to treatment time-RTT), however where possible sites should complete this procedure within 12 weeks post randomisation. During the study participants need to come to the hospital for another 4 visits where their hand is assessed, they are asked some questions about their hand function and general health, and a photograph is taken of their hand. |
| Intervention type | Drug |
| Phase | Phase IV |
| Drug / device / biological / vaccine name(s) | Collagenase Clostridium histolyticum (CCH) |
| Primary outcome measure(s) |
Hand health and overall hand assessment, measured using the Patient Evaluation Measure at baseline, pre treatment, 3 months, 6 months, 1 year and 2 years post treatment |
| Key secondary outcome measure(s) |
Current secondary outcome measures as of 31/10/2018: |
| Completion date | 31/07/2022 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | All |
| Target sample size at registration | 710 |
| Total final enrolment | 673 |
| Key inclusion criteria | 1. Male or female and aged 18 years or over 2. Presence of discrete, palpable, contracted cord involving the metacarpophalangeal joint and/or proximal interphalangeal joint of a finger 3. Degree of contracture ≥30 degrees in either joint i.e. patient cannot put the palm of the hand flat on a table (Hueston’s Table top test) 4. Able to identify a predominant cord for treatment which would not require more than one Collagenase injection as treatment 5. Appropriate for limited fasciectomy surgery and Collagenase injection for Dupuytren’s contracture (i.e. cords suitable for CCH and limited fasciectomy and not requiring skin grafting or PNF (e.g. discrete MCP cords in elderly)) 6. Patient is willing and able to give informed consent for participation in the study |
| Key exclusion criteria | Current exclusion criteria as of 31/10/2018: 1. Severe contractures of both metacarpophalangeal joint and/or proximal interphalangeal joints (Tubiana Grade 4) 2. History of previous intervention for Dupuytren’s contracture (e.g. surgery, Collagenase injection or needle fasciectomy) to the study reference digit 3. History of any other pre-existing disorder of the hand causing significant restriction of movement and/or pain and affecting hand function e.g. post traumatic stiffness, stiffness due to other causes, infection, arthritis 4. Non-English speaking because of the need to complete multiple questionnaires which have not been validated in multiple languages 5. Resident in a location where attendance for follow up at one of the study recruiting centres will not be possible 6. Contraindicated for use of Collagenase including hypersensitivity to: Collagenase, Sucrose, Ketorolac Trometamol, hydrochloric acid, calcium chloride dehydrate, sodium chloride 7. Diagnosis of a coagulation disorder 8. Any other significant disease or disorder (including autoimmune disorders) which, in the opinion of the Investigator, may put the participant at risk because of participation in the study, or may influence the result of the study, or the participant’s ability to participate in the study 9. Participation in another research study involving an investigational product in the past 12 weeks 10. Female participants who report to be pregnant or breastfeeding Previous exclusion criteria: 1. Severe contractures of both metacarpophalangeal joint and/or proximal interphalangeal joints (Tubiana Grade 4) 2. History of previous intervention for Dupuytren’s contracture (e.g. surgery, Collagenase injection or needle fasciectomy) on the same hand 3. History of any other pre-existing disorder of the hand causing significant restriction of movement and/or pain and affecting hand function e.g. post traumatic stiffness, stiffness due to other causes, infection, arthritis 4. Non-English speaking because of the need to complete multiple questionnaires which have not been validated in multiple languages 5. Resident in a location where attendance for follow up at one of the study recruiting centres will not be possible 6. Contraindicated for use of Collagenase including hypersensitivity to: Collagenase, Sucrose, Ketorolac Trometamol, hydrochloric acid, calcium chloride dehydrate, sodium chloride 7. Diagnosis of a coagulation disorder 8. Any other significant disease or disorder (including autoimmune disorders) which, in the opinion of the Investigator, may put the participant at risk because of participation in the study, or may influence the result of the study, or the participant’s ability to participate in the study 9. Participation in another research study involving an investigational product in the past 12 weeks 10. Female participants who report to be pregnant or breastfeeding |
| Date of first enrolment | 01/05/2017 |
| Date of final enrolment | 31/03/2021 |
Locations
Countries of recruitment
- United Kingdom
- England
Study participating centres
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
United Kingdom
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| IPD sharing plan | The current data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Results article | 09/10/2024 | 10/10/2024 | Yes | No | |
| Protocol article | 30/09/2021 | 19/10/2021 | Yes | No | |
| HRA research summary | 28/06/2023 | No | No | ||
| Other files | Health economics analysis plan version 1.0 |
29/09/2021 | 03/02/2023 | No | No |
| Other files | Results Infographic version 1.0 |
19/06/2023 | 06/11/2024 | No | No |
| Other unpublished results | End of Study Report version 1.0 |
15/06/2023 | 06/11/2024 | No | No |
| Participant information sheet | Participant information sheet | 11/11/2025 | 11/11/2025 | No | Yes |
| Statistical Analysis Plan | version 1.0 | 29/09/2021 | 03/02/2023 | No | No |
| Study website | Study website | 11/11/2025 | 11/11/2025 | No | Yes |
Additional files
- ISRCTN18254597_SAP_V1.0_29Sep21.pdf
- Statistical Analysis Plan
- ISRCTN18254597_HealthEconomicsAnalysisPlan_V1.0_29Sep21.pdf
- Health economics analysis plan
- ISRCTN18254597 17YH0120_DISC Trial End of Study Report v1.0 15.06.2023.pdf
- End of Study Report
- ISRCTN18254597 DISC Results Infographic v1.0 19.06.2023.pdf
- Results Infographic
Editorial Notes
06/11/2024: Unpublished results files were uploaded.
10/10/2024: Publication reference added.
03/02/2023: Statistical analysis plan and health economics analysis plan uploaded.
18/07/2022: The intention to publish date was changed from 30/11/2022 to 30/06/2024.
19/10/2021: The following changes have been made:
1. The overall trial end date has been changed from 31/10/2021 to 31/07/2022 and the plain English summary has been updated to reflect this change.
2. The intention to publish date has been changed from 30/04/2022 to 30/11/2022.
3. The total final enrolment number has been added.
4. Publication reference added.
18/11/2020: The following changes were made to the trial record:
1. The interventions were updated.
2. The plain English summary was updated.
27/08/2020: Recruitment to this study is no longer paused. The recruitment end date has been changed from 30/09/2020 to 31/03/2021.
16/04/2020: Due to current public health guidance, recruitment for this study has been paused.
04/11/2019: The recruitment end date has been changed from 31/10/2019 to 30/09/2020.
31/10/2018: The following changes have been made:
1. The plain English summary has been changed.
2. The participant exclusion criteria have been changed.
3. The secondary outcome measures have been changed.
19/09/2017: Mrs Michelle Watson (michelle.watson@york.ac.uk) has been removed as a study contact. Puvan Tharmanathan has been added (Puvan.nathan@york.ac.uk).
31/08/2017: Ethics information has been added.
