Decellularised Dermis Allograft for the Treatment of Chronic Venous Leg Ulceration (DAVE)

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

Study Overview

• Status: Terminated
• Conditions: Venous Ulcer; Allograft
• Intervention / Treatment: Other: Compression bandaging therapy; Other: dCELL® Human Dermis (decellularised dermal skin allograft - DCD)

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.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Bristol, United Kingdom
    • North Bristol NHS Trust
  • Cardiff, United Kingdom
    • Cardiff and Vale University Health Board
  • Carlisle, United Kingdom
    • North Cumbria University Hospitals NHS Trust
  • Gloucester, United Kingdom
    • Gloucestershire Hospitals NHS Foundation Trust
  • London, United Kingdom
    • Imperial College Healthcare NHS Trust
  • London, United Kingdom
    • Guy's and St Thomas' NHS Foundation Trust
  • London, United Kingdom
    • London North West University Healthcare
  • London, United Kingdom
    • AT Medics
  • London, United Kingdom
    • St Charles Centre for Health and Welbeing, Central London Community Healthcare NHS Trust
  • Newport, United Kingdom
    • Aneurin Bevan University Health Board
  • Northampton, United Kingdom
    • Northampton General Hospital NHS Trust
  • Plymouth, United Kingdom
    • University Hospitals Plymouth NHS Trust
  • Plymouth, United Kingdom
    • Livewell
  • Swansea, United Kingdom
    • Swansea Bay University Health Board
  • Taunton, United Kingdom
    • Taunton and Somerset NHS Foundation Trust
  • Wakefield, United Kingdom
    • Mid Yorkshire Hospitals NHS Trust
  • Worcester, United Kingdom
    • Worcestershire Acute Hospitals NHS Trust

Participation Criteria

Eligibility Criteria

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

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard care arm; Compression bandaging therapy as per standard care	Other: Compression bandaging therapy; Compression therapy will be according to local practice and may include multilayer elastic compression bandaging or stockings delivering 20 to 40mm/Hg pressure.
Experimental: DCD Arm; DCD graft plus compression bandaging therapy as per standard care	Other: Compression bandaging therapy; Compression therapy will be according to local practice and may include multilayer elastic compression bandaging or stockings delivering 20 to 40mm/Hg pressure.; Other: dCELL® Human Dermis (decellularised dermal skin allograft - DCD); DCD is produced from split thickness skin grafts (which comprise the epidermis and upper part of the dermis), and is retrieved from deceased tissue donors. All epidermal and cellular components from the dermis are removed in a patented sequential decellularisation process. As a decellularised graft, dCELL® Human Dermis fully integrates into the wound bed after application, replacing lost dermal tissue. It provides a scaffold into which the recipient's cells can grow, becoming vascularised and supporting the generation of a new epidermis, ultimately regenerating into normal skin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion with a healed index ulcer at 12 weeks after randomisation.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to index ulcer healing from randomisation		12 months
The percentage change in index ulcer area in cm2 at 12 weeks from randomisation		12 weeks
The proportion of participants with a healed index ulcer at 12 months from randomisation		12 months
The proportion of participants whose index ulcer healed for whom an ulcer recurred at the index site within 12 months from randomisation		12 months
Generic quality of life using the EuroQol-5D (EQ-5D) questionnaire	A health index on a score of 0 to 1 and the participants' self-rated health on a vertical score of zero to 100. Higher scores indicate better quality of life	12 weeks, 6 months and 12 months from randomisation
Disease specific quality of life using the Charing Cross Venous Ulcer Questionnaire (CCVUQ)	Scale 0 to 100, with lower scores indicating better quality of life	12 weeks, 6 months and 12 months from randomisation
The cost for each patient, calculated from the healthcare resources used		12 months
Incremental cost-effectiveness ratio (ICER) from the EQ-5D questionnaire, with appropriate sensitivity analysis	An intervention may be considered cost-effective when its ICER is less than the threshold set by health policy decision-makers. In the UK, the cost-effectiveness threshold is currently in the range £20 000-30 000 per QALY	12 months

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Cambridge University Hospitals NHS Foundation Trust; University of Edinburgh; University of Manchester; University of Birmingham; Universidad de Granada; Gloucestershire Hospitals NHS Foundation Trust; NHS Blood and Transplant
• Investigators: Principal Investigator: Alun H Davies, Imperial College London

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2019
• Primary Completion (Actual): April 10, 2023
• Study Completion (Actual): April 10, 2023

Study Registration Dates

• First Submitted: July 9, 2019
• First Submitted That Met QC Criteria: July 15, 2019
• First Posted (Actual): July 16, 2019

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Ulcer; Compression therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Leg Ulcer; Skin Ulcer; Varicose Veins; Varicose Ulcer
• Other Study ID Numbers: 19CX5371

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: IPD sharing will be in line with Imperial College data sharing policy

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No