Clinical Trial Results:
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.
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Summary
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EudraCT number |
2016-004251-76 |
Trial protocol |
GB |
Global end of trial date |
31 Jul 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Jun 2025
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First version publication date |
12 Jun 2025
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
87230
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Additional study identifiers
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ISRCTN number |
ISRCTN18254597 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
University Hospitals of Leicester NHS Trust
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Sponsor organisation address |
Trust HQ, Level 3 Balmoral Building, Leicester Royal Infirmary, Leicester, United Kingdom, LS1 5WW
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Public contact |
Catherine Arundel, York Trials Unit, University of York, catherine.arundel@york.ac.uk
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Scientific contact |
Catherine Arundel , York Trials Unit, University of York, catherine.arundel@york.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
31 Jul 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Jul 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jul 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To investigate whether collagenase injection is as good as surgery (limited fasciectomy) in the correction of Dupuytren’s contracture of the hand
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Protection of trial subjects |
Treated in routine UK NHS Care
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Background therapy |
Not applicable | ||
Evidence for comparator |
Dupuytren’s disease affects over 2 million UK adults; cords pull the fingers down towards the palm. This interferes with hand function and dexterity, impacting on quality of life. Current treatments to remove, dissolve or break the cords include surgical correction (limited fasciectomy), collagenase injection (an enzyme injected into the cord), and percutaneous needle fasciotomy (a needle is used to puncture, weaken, and cut the cord). None of these treatments cure the tendency to develop DC and so the cords and contracture can recur over time. Collagenase has some benefits over limited fasciectomy (LF) surgery including shorter recovery and no dependence on operating theatre availability for delivery of the intervention. There is, however, limited robust evidence comparing surgical correction and collagenase injection in terms of clinical effectiveness, cost effectiveness and in terms of patient’s experiences and preferences. | ||
Actual start date of recruitment |
01 May 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 672
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Worldwide total number of subjects |
672
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
268
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From 65 to 84 years |
396
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85 years and over |
8
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Recruitment
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Recruitment details |
The DISC trial was a multicenter, open-label, pragmatic, parallel two-arm randomized controlled non-inferiority trial. The 31 recruiting sites were UK National Health Service hand units. Participants were recruited from 31st July 2017 to 28th September 2021. | |||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Patients aged 18 years and over with a discrete, palpable Dupuytren’s cord causing contracture of ≥30° and who were appropriate for both study treatments were eligible for inclusion. | |||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Intervention (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||||||||
Blinding implementation details |
Given the pragmatic nature of the trial, and the surgical and injection interventions used, it was not possible to blind clinicians or participants to study allocation. It was also not possible to blind the analysing statistician to trial allocation due to the way in which data were collected. To mitigate any impact of this, a statistical analysis plan (available at: https://www.isrctn.com/ISRCTN18254597) pre-specified all analyses and any changes made to the data set prior to analysis were docu
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Intervention - Collagenase Clostridium Histolyticum | |||||||||||||||||||||||||||
Arm description |
Collagenase clostridium histolyticum | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Collagenase Clostridium Histolyticum
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for injection
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Routes of administration |
Injection
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Dosage and administration details |
Depending on the cord affected 0.25ml or 0.20ml of reconstituted solution (0.58mg Collagenase Clostridium histolyticum) was injected as three aliquots: 0.25ml for cord in a metacarpophalangeal joint, 0.20ml for cord in a proximal interphalangeal joint.
The three aliquots were distributed via injection into an affected cord at set anatomical points through a single needle puncture at a single time point. If separate cords were to be injected at the same treatment visit, this was be permitted but a reference cord (i.e. predominant) must be identified.
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Arm title
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Control - Limited Fasciectomy | |||||||||||||||||||||||||||
Arm description |
Limited Fasciectomy | |||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||
Investigational medicinal product name |
Surgical Intervention
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Not assigned
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Routes of administration |
Unknown use
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Dosage and administration details |
The control treatment for the DISC trial was limited fasciectomy, a standard technique in Europe for treatment of Dupuytren’s contracture. This procedure involves the removal, under anaesthesia, of the diseased fascia, nodule and cord, or a part of it, to correct the contracture of the joint. Tourniquet control may be used if required.
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Baseline characteristics reporting groups
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Reporting group title |
Intervention - Collagenase Clostridium Histolyticum
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Reporting group description |
Collagenase clostridium histolyticum | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control - Limited Fasciectomy
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Reporting group description |
Limited Fasciectomy | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Primary Analysis - Intervention Group
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Primary analysis subject set 314 intervention participants who provided primary outcome data that contributed to the primary analysis
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Subject analysis set title |
Primary Analysis - Control Group
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Primary outcome analysis of 285 control participants who provided primary outcome data that contributed to the primary analysis,
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End points reporting groups
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Reporting group title |
Intervention - Collagenase Clostridium Histolyticum
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Reporting group description |
Collagenase clostridium histolyticum | ||
Reporting group title |
Control - Limited Fasciectomy
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Reporting group description |
Limited Fasciectomy | ||
Subject analysis set title |
Primary Analysis - Intervention Group
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Primary analysis subject set 314 intervention participants who provided primary outcome data that contributed to the primary analysis
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Subject analysis set title |
Primary Analysis - Control Group
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Primary outcome analysis of 285 control participants who provided primary outcome data that contributed to the primary analysis,
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End point title |
PRIMARY OUTCOME Change in PEM score between Baseline and 1 year post treatment | |||||||||||||||
End point description |
The primary endpoint was the score obtained for the 11 items in part two of the PEM at 1 year after treatment (0 – 100, with higher scores indicating worse outcome).
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End point type |
Primary
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End point timeframe |
Change in score between Baseline and 1 year post treatment
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Statistical analysis title |
Primary outcome analysis - Analysis Sets | |||||||||||||||
Statistical analysis description |
A covariance pattern model, with all PEM measurements taken after treatment included as outcomes, was used to estimate the between group differences (Collagenase – LF) in expected PEM score at each time point after treatment. Treatment group and time point and their interaction were included as fixed effects. This model also included fixed effects for study reference joint (stratification factor) and baseline PEM score and a random intercept of recruiting site
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Comparison groups |
Primary Analysis - Intervention Group v Primary Analysis - Control Group
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Number of subjects included in analysis |
599
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | |||||||||||||||
P-value |
= 0.49 | |||||||||||||||
Method |
t-test, 1-sided | |||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||
Point estimate |
5.9
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
3.1 | |||||||||||||||
upper limit |
8.8 | |||||||||||||||
Statistical analysis title |
Primary outcome analysis - Reporting Groups | |||||||||||||||
Statistical analysis description |
A covariance pattern model, with all PEM measurements taken after treatment included as outcomes, was used to estimate the between group differences (Collagenase – LF) in expected PEM score at each time point after treatment. Treatment group and time point and their interaction were included as fixed effects. This model also included fixed effects for study reference joint (stratification factor) and baseline PEM score and a random intercept of recruiting site
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Comparison groups |
Intervention - Collagenase Clostridium Histolyticum v Control - Limited Fasciectomy
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Number of subjects included in analysis |
599
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | |||||||||||||||
P-value |
= 0.49 | |||||||||||||||
Method |
t-test, 1-sided | |||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||
Point estimate |
5.9
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Confidence interval |
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level |
95% | |||||||||||||||
sides |
2-sided
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lower limit |
3.1 | |||||||||||||||
upper limit |
8.8 | |||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
24 months
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10
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Reporting groups
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Reporting group title |
Intervention - Collagenase Clostridium Histolyticum
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Reporting group description |
Collagenase clostridium histolyticum | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control - Limited Fasciectomy
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Reporting group description |
Limited Fasciectomy | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Date |
Amendment |
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02 Jul 2018 |
Amendment to study to implement revised (updated) Simplified Product Characteristics (SmPC) document for the associated IMP (Xiapex).
The changes made to the SmPC were as follows:
- Addition of a further uncommon event to the list of adverse reactions for Dupuytren’s Contracture (General disorders and administration site conditions - Cold intolerance to treated fingers)
- Reformatting of Annex 1 - Section 6.6 to separate information relating to reconstitution of the IMP for Peyronies disease and Dupuytren’s contracture (This amendment did not impact on the DISC Trial) |
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16 Oct 2018 |
Amendments made to study protocol requiring regulatory authority approval.
This substantial amendment included changes to the protocol, to improve recruitment conversion rates and pathways and to reduce the activity burden on study sites, and to the PIS to reflect amendments made to the protocol and to include GDPR transparency information. |
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14 Jul 2020 |
This substantial amendment included revisions to monitoring plan for the study (as originally detailed in the DISC MHRA Risk Assessment and Safety Monitoring) and a revised (updated) Simplified Product Characteristics (SPC) for the study IMP (Xiapex).
Changes to the SPC, relevant to Dupuytren’s Contracture inclued:
- Addition of further precautions, for use in treatment of Dupuytren’s contracture (i.e. reported cases of finger necrosis linked to pre-existing reduced peripheral circulation; cases of digital phalangeal fractures following finger manipulation in patients with bone fragility) and Peyronie’s disease (i.e. to reduce risk of Corporal rupture) (Annex 1 - Section 4.4)
- Addition of a further two events to the list of adverse reactions for Dupuytren’s contracture of an unknown incidence (i.e. digital necrosis and digital fracture).
- Combining of information relating to treatment area selection for Peyronie’s disease and Dupuytren’s contracture (Annex 1 – Section 6.6)
- Addition of information to the patient leaflet warning of the risk of finger necrosis or fracture and advising patients to inform their doctor if they have a condition affecting their bones. Addition of side effects for Dupuytren’s contracture where frequency is not known (i.e. fractures finger and loss of finger or finger parts) (Annex III – Section B)
- Reformatting of the order of information for healthcare professionals (Annex III – Section B) |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| None reported | |||||||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/39383454 http://www.ncbi.nlm.nih.gov/pubmed/39644138 |
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