Wool-derived Keratin Dressings for Venous Leg Ulcers (Keratin4VLU)

Keratin4VLU: A Randomised Controlled Trial of Wool-derived Keratin Dressings for Venous Leg Ulcers

Venous leg ulcers (VLU) are the most common leg ulcer, can be painful, and limit work, lifestyles and activity, especially in older patients. Compression bandaging is the main treatment but there are few added treatments for patients with slow healing VLU. About 50% of patients with VLU may be slow healing. Research suggests using keratin dressings as well as using compression may help healing in patients with show healing VLU, but the current evidence is not enough to change clinical practice. The investigators will conduct a randomised controlled trial to test whether using keratin dressings is better than usual care for slow healing VLU.

Study Overview

• Status: Completed
• Conditions: Varicose Ulcer
• Intervention / Treatment: Device: Keratin dressings; Device: Usual care dressings

Detailed Description

A pragmatic, community based, single-blind, usual care-controlled, randomised trial to determine whether keratin dressings increase the proportion of patients with venous leg ulcers healed at 24 weeks when used in addition to compression in patients with slow healing venous leg ulcers. Participants in have compression therapy (system of choice guided by patient and/or clinical preference) as delivered through district nursing services at the study centres as a background treatment. Keratin dressings will be applied when the compression bandage is changed (approximately weekly). Usual care dressings will consist of the usual formulary of moist wound dressings available at each study centre.

Participants will be district nursing service patients in five study centres in New Zealand with prevalent or incident venous leg ulcers. A venous leg ulcer will be defined as a wound on the lower leg that has remained unhealed for 4 or more weeks, appears to be primarily venous in aetiology with other causative diseases ruled out. If the participant has two or more venous leg ulcers, the largest ulcer will be the reference ulcer. A participant will be considered to have a slow healing venous leg ulcer if the ulcer area is larger than 5 cm2 and/or the ulcer has been present for more than six months.

Participants will receive up to four visits from the research nurse - visit 1 to screen for eligibility, visit 2 to consent and randomise the participant, visits 3 and 4 to collect outcome data. District nurses will continue to visit the participant (about weekly or more frequently if required) to provide routine care between research nurse visits.

Block randomisation will be used, stratified by study centre and prognostic index (ulcer size greater than 5cm2 and/or ulcer duration greater than 6 months) to ensure a balance of participants within study centres and for participants likely to be slow healers. Research nurses will input information on inclusion criteria, exclusion criteria, and relevant clinical history on consented participants via a tablet computer. The allocation will be generated after this information has been entered. Randomised participants will receive the allocated treatment until the reference ulcer heals or data collection is completed, whichever occurs sooner.

• Study Type: Interventional
• Enrollment (Actual): 143
• Phase: Not Applicable

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand
    • University of Auckland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical indications of venous leg ulceration
• Ankle Brachial Index ≥ 0.7
• Able to tolerate compression therapy
• Ulcer area > 5cm2 and/or ulcer duration > 6 months
• Able to provide informed consent.

Exclusion Criteria:

• Hypersensitivity to wool or wool alcohols
• Venous leg ulceration with exposed tendon or bone
• Infected venous leg ulcer at trial inception (eligible after infection resolved)
• Venous leg ulcer with critical bioburden at trial inception (eligible if resolved)
• History of rheumatoid arthritis or vasculitis
• Uncontrolled diabetes
• Severe liver, heart, or renal failure
• Severe peripheral arterial disease
• Suspected or diagnosed skin malignancy
• Other threat to safe participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Keratin dressings; Wool-derived keratin matrix dressing applied with each change of the compression bandage until healing	Device: Keratin dressings; Wool-derived keratin matrix dressings applied with each change of the compression bandage until healing or the trial ends
Active Comparator: Usual care dressings; Dressing chosen from study centres' formulary of non-medicated moist wound dressings applied with each change of the compression bandage until healing	Device: Usual care dressings; Dressings chosen from study centres' formulary of non-medicated moist wound dressings (non-adherent dressings, hydrogel, alginate, hydrofibre or polyurethane foam dressings) applied with each change of the compression bandage until healing or the trial ends

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients with complete healing of reference ulcer	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Agreement between blinded and unblinded assessors on healing		24 week outcome
Time to complete healing of reference ulcer		Until data collection completed two years after first participant is recruited
Change in estimated reference ulcer area	Estimated ulcer area will be derived measuring maximum width and length to determine area using formula for area of an ellipse. Such an approach is highly co-related (r=0.92) with more sophisticated measurement methods.	24 weeks
Change in health-related quality of life (generic)	The RAND-36 questionnaire will be used for measurement of generic health-related quality of life	24 weeks
Change in health-related quality of life (generic)	The EuroQuol-5D questionnaire will be used to generate utility values for cost-effectiveness modelling should that be undertaken	24 weeks
Change in health-related quality of life (disease-specific)	The Charing Cross Venous Ulcer Questionnaire will be used for measurement of disease-specific health-related quality of life	24 weeks
Incidence of adverse events		Until data collection completed two years after first participant is recruited

Collaborators and Investigators

• Sponsor: University of Auckland, New Zealand
• Collaborators: Health Research Council, New Zealand
• Investigators: Principal Investigator: Andrew Jull, RN PhD, National Institute for Health Innovation, University of Auckland

Publications and helpful links

General Publications

• Jull A, Wadham A, Bullen C, Parag V, Waters J. Wool-derived keratin dressings versus usual care dressings for treatment of slow-healing venous leg ulceration: study protocol for a randomised controlled trial (Keratin4VLU). BMJ Open. 2018 Feb 13;8(2):e020319. doi: 10.1136/bmjopen-2017-020319.
• Jull A, Wadham A, Bullen C, Parag V, Weller C, Waters J. Wool-derived keratin dressings versus usual care dressings for treatment of slow healing venous leg ulceration: a randomised controlled trial (Keratin4VLU). BMJ Open. 2020 Jul 20;10(7):e036476. doi: 10.1136/bmjopen-2019-036476.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2017
• Primary Completion (Actual): February 28, 2019
• Study Completion (Actual): September 30, 2019

Study Registration Dates

• First Submitted: August 29, 2016
• First Submitted That Met QC Criteria: September 6, 2016
• First Posted (Estimate): September 12, 2016

Study Record Updates

• Last Update Posted (Actual): July 24, 2020
• Last Update Submitted That Met QC Criteria: July 22, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Venous leg ulcer; Acellular skin substitutes; Keratin dressings
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Skin Ulcer; Varicose Veins; Ulcer; Leg Ulcer; Varicose Ulcer
• Other Study ID Numbers: Keratin4VLU; U1111-1186-5202 (Other Identifier: World Health Organisation Universal Trial Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Anonymised individual participant data may be made available on request to the Principal Investigator

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No