Clinical trial NCT04021316: Decellularised Dermis Allograft for the Treatment of Chronic Venous Leg Ulceration
Official title: Decellularised Dermis Allograft for the Treatment of Chronic Venous Leg Ulceration
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Venous Ulcer
Allograft
Keywords: Compression therapy
Ulcer
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: University of Edinburgh
name: Universidad de Granada
name: University of Manchester
name: Gloucestershire Hospitals NHS Foundation Trust
name: Cambridge University Hospitals NHS Foundation Trust
name: University of Birmingham
name: NHS Blood and Transplant
First posted: 2019-07-16
Enrollment: 71
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will undergo 1:1 web based randomisation to either standard care or the intervention via an automated system. A minimization algorithm using centre, index ulcer size and duration will be used, including a random component to lessen predictability. A separate Randomisation System Description document will contain full details of the cut-offs for index ulcer size and duration, and the probability that the allocation will be switched.
Primary purpose: TREATMENT

Brief summary: Does the use of decellularised dermis allograft in addition to compression therapy promote healing in chronic venous leg ulceration compared to compression therapy alone

Detailed description: Chronic venous ulceration are open wounds on the lower limbs which have been present for at least three months and are caused by a poorly functioning venous system. The affect about 1% of the general population and about 4% of those over 65. The wounds cause pain, reduced movement, and can smell - greatly affecting the quality of life of leg ulcer patients. The standard care for these patients is compression bandaging, which requires changing several times a week by community or district nurses; this drives the high cost of leg ulcer care, which can amount to £2.5 billion per annum.

Skin grafting can be used alongside compression bandaging and can help the ulcers heal faster than compression alone. Grafts can be taken from the patient's own skin, from a donor or from tissue engineered skin. An autograft (using own skin) can cause scarring and the need for a formal surgical procedure in theatre so are not suitable for all ulcer patients. Allografts (donor skin) and xenografts (animal skin) have been used successfully, but present similar drawbacks to autografts, plus the potential for the body to reject the graft and disease transmission. Tissue engineered skin has several advantages as it has been processed to remove the cells, and therefore is won't be rejected via the immune response. Human decellularised dermis (DCD) is generated from donated skin from deceased people and processed to remove the cells. It can be glued or sewn onto the skin under local anesthetic, in an out patient setting. DCD has mainly been studied in patients with diabetic foot ulceration and has shown improved healing rates and quality of life.

This study will investigate the use of DCD in addition to compression therapy versus compression therapy alone in patients with chronic venous leg ulceration.

Eligibility criteria: Inclusion Criteria:

* ≥18 years or older (no upper age limit)
* The ability to consent to participation
* A diagnosis of venous leg ulceration\* (defined as 'colour duplex confirmation of superficial and or deep venous reflux with any break in the skin that has either: a) been present for more than 2 weeks, or b) occurred in a person with a history of venous leg ulceration)
* Documented venous incompetence on duplex ultrasound
* Index ulcer wound duration of greater than 3 months
* Index ulcer wound size ≥ 2 cm2.
* ABPI ≥ 0.8

  * in light of the Covd-19 pandemic, the use of handheld continuous wave Dopplers will be allowed to diagnose venous disease to allow participants to be recruited from clinic without the need for an imaging appointment

Exclusion Criteria:

* A diagnosis of sickle cell
* Unable to receive one or more of the randomised treatment strategies for any reason at the discretion of the attending clinical team (e.g. known allergies to dCELL dermis preparation components)
* A clinically infected ulcer defined as evidence of erythema, cellulitis or systemically unwell
* Treatment with biomedical/topical growth factors within previous 30 days
* Previous history of an inability to tolerate compression therapy
* Foot ulcer (i.e. below the ankle)

Primary outcomes:
measure: Proportion with a healed index ulcer at 12 weeks after randomisation.
timeFrame: 12 weeks
Secondary outcomes:
measure: Time to index ulcer healing from randomisation
timeFrame: 12 months
measure: The percentage change in index ulcer area in cm2 at 12 weeks from randomisation
timeFrame: 12 weeks
measure: The proportion of participants with a healed index ulcer at 12 months from randomisation
timeFrame: 12 months
measure: The proportion of participants whose index ulcer healed for whom an ulcer recurred at the index site within 12 months from randomisation
timeFrame: 12 months
measure: Generic quality of life using the EuroQol-5D (EQ-5D) questionnaire
timeFrame: 12 weeks, 6 months and 12 months from randomisation
measure: Disease specific quality of life using the Charing Cross Venous Ulcer Questionnaire (CCVUQ)
timeFrame: 12 weeks, 6 months and 12 months from randomisation
measure: The cost for each patient, calculated from the healthcare resources used
timeFrame: 12 months
measure: Incremental cost-effectiveness ratio (ICER) from the EQ-5D questionnaire, with appropriate sensitivity analysis
timeFrame: 12 months
Other outcomes:
Locations:
city: Bristol
country: United Kingdom
facility: North Bristol NHS Trust
city: Cardiff
country: United Kingdom
facility: Cardiff and Vale University Health Board
city: Carlisle
country: United Kingdom
facility: North Cumbria University Hospitals NHS Trust
city: Gloucester
country: United Kingdom
facility: Gloucestershire Hospitals NHS Foundation Trust
city: London
country: United Kingdom
facility: AT Medics
city: London
country: United Kingdom
facility: Guy's and St Thomas' NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: London
country: United Kingdom
facility: London North West University Healthcare
city: London
country: United Kingdom
facility: St Charles Centre for Health and Welbeing, Central London Community Healthcare NHS Trust
city: Newport
country: United Kingdom
facility: Aneurin Bevan University Health Board
city: Northampton
country: United Kingdom
facility: Northampton General Hospital NHS Trust
city: Plymouth
country: United Kingdom
facility: Livewell
city: Plymouth
country: United Kingdom
facility: University Hospitals Plymouth NHS Trust
city: Swansea
country: United Kingdom
facility: Swansea Bay University Health Board
city: Taunton
country: United Kingdom
facility: Taunton and Somerset NHS Foundation Trust
city: Wakefield
country: United Kingdom
facility: Mid Yorkshire Hospitals NHS Trust
city: Worcester
country: United Kingdom
facility: Worcestershire Acute Hospitals NHS Trust
Study officials:
affiliation: Imperial College London
name: Alun H Davies
role: PRINCIPAL_INVESTIGATOR
References: