Clinical trial NCT02158806: Low Dose Aspirin for Venous Leg Ulcers
Official title: Low Dose Aspirin for Venous Leg Ulcers: a Randomised Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Venous Leg Ulcer
Keywords: Venous ulcer, varicose ulcer, gravitational ulcer, aspirin
Lead sponsor: University of Auckland, New Zealand
Sponsor class: OTHER
Collaborators: name: Health Research Council, New Zealand
First posted: 2014-06-09
Enrollment: 251
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: Venous leg ulcers (VLU) are the most common leg ulcer, can be painful, and limit work, lifestyles and activity, especially in older patients. There are few effective treatments - compression therapy (tight bandaging or stockings) helps healing, but about half the people with a VLU remain unhealed even after 12 weeks of treatment. Research suggests taking aspirin as well as using compression may speed up healing for VLU, but the current evidence is not enough to change clinical practice. We will conduct a randomised controlled trial to test whether using low dose aspirin (150 mg daily or placebo) really does speed up healing.

Detailed description: A pragmatic, community based, double-blind, placebo-controlled, randomised trial to determine whether low dose aspirin accelerates venous leg ulcer healing at 24 weeks when used in addition to compression. 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. Low dose aspirin (150 mg) or placebo will be taken once daily as an oral capsule.

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.

Participants will receive three visits from the research nurse - visit 1 to screen for eligibility, visit 2 to consent and randomise the participant, visit 3 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 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 in the study centres will contact a central telephone answering service, provide information on inclusion criteria, exclusion criteria, and relevant clinical history on consented participants. Randomised participants will receive a bottle of 168 capsules of study medication identified only by unique code and will take the capsule until the reference ulcer heals or up to 24 weeks, whichever occurs sooner.

Participants will take the study medication for up to 24 weeks or until the reference ulcer heals. If the participant has a serious adverse event, needs to start taking aspirin, or must stop taking aspirin to use other medications, they will be withdrawn from treatment, although they will still be followed up at 24 weeks.

Eligibility criteria: Inclusion Criteria:

* Aged 18 years or older
* Determined to have a venous leg ulcer (clinical indications of venous ulceration, Ankle Brachial Index ≥ 0.8, and other causative aetiologies ruled out)
* Able to tolerate compression therapy
* Able to provide written informed consent
* Confirmation with participant's general practitioner that the participant can take low dose aspirin or placebo.

Exclusion Criteria:

* Pregnant or breast-feeding women
* History of myocardial infarction, stroke, transient ischaemic attack, angina or significant peripheral arterial disease
* History of adverse effects related to aspirin use
* Currently using aspirin, or other anti-platelet or anticoagulant therapy
* Opinion of screening medical practitioner at National Institute of Health Innovation that participant has an existing condition or treatment that is a contraindication to use of aspirin or to participation in the trial.

Primary outcomes:
measure: Time to Complete Healing of Reference Ulcer
timeFrame: 24 weeks
Secondary outcomes:
measure: Number of Participants With Healed Venous Leg Ulcers
timeFrame: 24 weeks
measure: Change in Estimated Ulcer Area
timeFrame: Baseline, 24 weeks
measure: Change in Health-related Quality of Life (Short Form 36)
timeFrame: Baseline, 24 weeks
measure: Change in Health-related Quality of Life (EuroQol-5D 3L)
timeFrame: Baseline, 24 weeks
measure: Change in Health-related Quality of Life (Charing Cross Venous Ulcer Questionnaire)
timeFrame: 24 weeks
measure: Number of Participants With Adherence to Treatment
timeFrame: 24 weeks
measure: Incidence of Adverse Events at 24 Weeks
timeFrame: 24 weeks
Other outcomes:
Locations:
Study officials:
affiliation: School of Nursing, University of Auckland
name: Andrew Jull, RN PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jull A, Wadham A, Bullen C, Parag V, Kerse N, Waters J. Low-dose aspirin as an adjuvant treatment for venous leg ulceration: study protocol for a randomized controlled trial (Aspirin4VLU). J Adv Nurs. 2016 Mar;72(3):669-79. doi: 10.1111/jan.12864. Epub 2015 Dec 28.
citation: Jull A, Wadham A, Bullen C, Parag V, Kerse N, Waters J. Low dose aspirin as adjuvant treatment for venous leg ulceration: pragmatic, randomised, double blind, placebo controlled trial (Aspirin4VLU). BMJ. 2017 Nov 24;359:j5157. doi: 10.1136/bmj.j5157.