Low Dose Aspirin for Venous Leg Ulcers

Study Overview
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Brief Summary
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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
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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.

Official Title
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Low Dose Aspirin for Venous Leg Ulcers: a Randomised Trial

Conditions
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Venous Leg Ulcer

Intervention / Treatment
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* Drug: Aspirin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aspirin<br>150 mg capsule once daily for up to 24 weeks | Drug: Aspirin<br>* 150 mg aspirin in capsule form once daily for up to 24 weeks<br>|
| Placebo Comparator: Inert capsule<br>Matching capsule once daily for up to 24 weeks | Drug: Placebo<br>* Matching placebo capsule containing inert bulking agent<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Complete Healing of Reference Ulcer | Time to event (complete healing defined as intact skin with absence of scab) | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Healed Venous Leg Ulcers | Number of participants in each arm with completely healed reference ulcers at 24 weeks | 24 weeks | 
| Change in Estimated Ulcer Area | Change in estimated ulcer area from baseline to 24 weeks | Baseline, 24 weeks | 
| Change in Health-related Quality of Life (Short Form 36) | Mean difference in change in Short Form 36 (SF36) from baseline to 24 weeks. Crude subscale scores for each group are not shown (each crude subscale is scored 0 to 100 at baseline and 24 weeks); higher mean differences in change from baseline to 24 weeks within groups indicate greater change on the subscales for that group. | Baseline, 24 weeks | 
| Change in Health-related Quality of Life (EuroQol-5D 3L) | Mean difference in change measured by EuroQol 5D (EQ5D 3L) from baseline to 24 weeks. Crude health state scores for each group are not shown (health state is scored 0 to 100 at baseline and 24 weeks); higher mean differences in change from baseline to 24 weeks within groups indicate greater change on health state for that group. | Baseline, 24 weeks | 
| Change in Health-related Quality of Life (Charing Cross Venous Ulcer Questionnaire) | Mean difference in change in Charing Cross Venous Ulcer Questionnaire (CXVUQ)) from baseline to 24 weeks. Crude subscale scores for each group are not shown (each crude subscale is scored 0 to 100 at baseline and 24 weeks); higher mean differences in change from baseline to 24 weeks within groups indicate greater change on the subscales for that group. | 24 weeks | 
| Number of Participants With Adherence to Treatment | Adherence to study medication as measured by pill counts (agreement between expected number of tablets remaining after healing and days to healing) | 24 weeks | 
| Incidence of Adverse Events at 24 Weeks | Total number of different types of adverse events in participants who reported with any untoward medical event | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Venous ulcer, varicose ulcer, gravitational ulcer, aspirin