Clinical trial NCT02333123: Aspirin for Venous Ulcers: Randomised Trial (AVURT)
Official title: Aspirin for Venous Ulcers: Randomised Trial (AVURT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Venous Leg Ulcer
Lead sponsor: St George's, University of London
Sponsor class: OTHER
Collaborators: name: University of York
name: University of Manchester
name: Bradford Teaching Hospitals NHS Foundation Trust
name: Harrogate & District NHS Foundation Trust
name: Hull University Teaching Hospitals NHS Trust
name: University of Nottingham
name: Cardiff University
name: University of Newcastle Upon-Tyne
First posted: 2015-01-07
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This efficacy study evaluates the safety and effectiveness of aspirin for venous leg ulcer healing. The study also examines whether patients can be recruited to a larger study. Patients with chronic venous leg ulceration presenting and undergoing care in leg ulcer community clinics or hospital out-patient clinics, or registered with a clinic but are receiving care at home will be recruited. All patients will receive standard compression bandaging. Half of the participants will be randomised to receive aspirin, while the other half will receive a placebo.

Detailed description: The mainstay of treatment of leg ulcers is graded compression therapy to squeeze the fluid out of the leg and venous system. This has been shown to be effective in many clinical trials. However, despite this treatment patients take many months to heal (with median healing times of approximately 12 weeks in previous trials) and for some patients compression therapy does not result in resolution of their leg ulcers. The use of compression (as well as dressings largely to manage the wound exudate) can be expensive as nurse time is required to change bandages which can be required weekly or more frequently. Furthermore, for many patients the compression therapy is uncomfortable (sometimes painful) and inconvenient for everyday life (compression is bulky and dressings have to be changed several times weekly). If other treatments were able to reduce the time to healing then this would be a significant breakthrough.

Results from two earlier small trials suggest aspirin may be of benefit. However this trials were poorly designed and reported. The present study will evaluate whether the addition of 300mg of daily aspirin to standard evidence based therapies reduces the time to healing of chronic venous leg ulceration using a more rigorous design. The study will also establish the feasibility of satisfactory participant recruitment for a bigger trial, and whether participants are compliant with their aspirin therapy. The safety of aspirin in this patient population will also be monitored.

Eligibility criteria: Inclusion Criteria:

* Those with at least one chronic venous leg ulcer - where chronic venous leg ulceration is defined as any break in the skin which has either: a) been present for more than six weeks, or b) occurred in a person with a history of venous leg ulceration. Ulcers will be considered purely venous if clinically no other etiology was suspected. For this the ulcer must be venous in appearance (i.e. moist, shallow, of an irregular shape) and lie wholly or partially within the gaiter region of the leg. If the patient has more than one ulcer we will choose the largest ulcer as the 'index' lesion for purposes of the analysis.
* Ulcer area \> 1 square cm
* Participants must have had an ankle brachial pressure index (ABPI) ≥ 0.8 taken within the previous three months. When the ABPI is incompressible other forms of assessment including peripheral pulse examination / toe pressure / duplex ultrasound in combination with clinical judgement to be used to exclude PAD
* Aged ≥ 18 years (no upper age limit)
* Able and willing to provide informed consent
* Ulcer duration \> 6 weeks or prior history of venous ulceration.

Exclusion Criteria:

* Unable to provide consent
* Unwilling to provide consent
* Foot (below the ankle) ulcer
* A leg ulcer of non-venous aetiology (i.e. arterial)
* Ankle-brachial pressure index (ABPI) \<0.8
* Current regular use of aspirin (as may be randomised to placebo)
* Previous intolerance of aspirin / contraindication to aspirin (decision made according to the prescribers' clinical judgement)
* Prohibited medication: Probenecid
* Known lactose intolerance (as placebo contains lactose)
* Pregnant/lactating women
* Currently participating in another study evaluating leg ulcer therapies.
* Another reason that excluded them from participating within this trial (decision made according to the nurses' or prescribers' clinical judgment )\*
* Previously been recruited in to this trial.

Primary outcomes:
measure: Time to healing of the reference ulcer (the largest eligible ulcer)
timeFrame: 25 weeks
Secondary outcomes:
measure: Ulcer size (area) measured in square cm
timeFrame: 25 weeks
measure: Recurrence of reference ulcer
timeFrame: 25 weeks
measure: Ulcer related pain using the VAS Score
timeFrame: 5 weeks
measure: Treatment concordance: number of participants completing the course of treatment
timeFrame: 24 weeks
measure: Resource use
timeFrame: 27 weeks
measure: Number of adverse events
timeFrame: 27 weeks
Other outcomes:
Locations:
city: Cottingham
country: United Kingdom
facility: Hull & East Yorkshire Hospital NHS Trust
state: Castle hill hosp
city: Tooting
country: United Kingdom
facility: St George's University Hospitals NHS Foundation Trust
state: London
city: Harrogate
country: United Kingdom
facility: Harrogate & district NHS Trust
state: N.Yorkshire
city: Brighton
country: United Kingdom
facility: Brighton General Hosp
state: Sussex
city: Newcastle Upon Tyne
country: United Kingdom
facility: Freeman Hospital
Study officials:
affiliation: St George's Healthcare NHS Trust
name: Robert J Hinchliffe, MD, FRCS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Helen T, Liz C, Laura C, Illary S, Martin B, Hannah B, Ian C, Jo D, Chris F, Rachael F, Rhian G, Keith H, Alison L, Ellie L, Catriona MD, Christine M, Debbie R, Gerard S, David T, Peter V, Laurie W, Robert H. Aspirin versus placebo for the treatment of venous leg ulcers-a phase II, pilot, randomised trial (AVURT). Trials. 2019 Jul 26;20(1):459. doi: 10.1186/s13063-019-3480-7.
citation: Tilbrook H, Clark L, Cook L, Bland M, Buckley H, Chetter I, Dumville J, Fenner C, Forsythe R, Gabe R, Harding K, Layton A, Lindsay E, McDaid C, Moffatt C, Rolfe D, Sbizzera I, Stansby G, Torgerson D, Vowden P, Williams L, Hinchliffe R. AVURT: aspirin versus placebo for the treatment of venous leg ulcers - a Phase II pilot randomised controlled trial. Health Technol Assess. 2018 Oct;22(55):1-138. doi: 10.3310/hta22550.
citation: Tilbrook H, Forsythe RO, Rolfe D, Clark L, Bland M, Buckley H, Chetter I, Cook L, Dumville J, Gabe R, Harding K, Layton A, Lindsay E, McDaid C, Moffatt C, Phillips C, Stansby G, Vowden P, Williams L, Torgerson D, Hinchliffe RJ. Aspirin for Venous Ulcers: Randomised Trial (AVURT): study protocol for a randomised controlled trial. Trials. 2015 Nov 10;16:513. doi: 10.1186/s13063-015-1039-9.