MIST Ultrasound Therapy Compared to United Kingdom Standard Care for the Treatment of Non-healing Venous Leg Ulcers

Study Overview
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Brief Summary
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Chronic venous leg ulcers (VLUs) impact negatively on patients' quality of life. Standard treatment in the UK for patients with VLUs is compression bandaging or stockings. The MIST ultrasound system is a noncontact device which delivers low frequency ultrasound through a gentle saline mist directed at a patient's wound. This study aims to determine whether the use of the MIST device used in combination with standard treatments can improve healing of VLUs compared to UK standard practice. This will be assessed by measuring any reduction in wound size in the two groups after receiving 8 weeks of either Standard Care once a week or MIST combined with Standard Care three times a week.

Detailed Description
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Venous leg ulcers (VLUs) are wounds which are often chronic and difficult to heal. VLUs affect between 1 and 3.2 people per 1000; they cause pain, reduced mobility and impact negatively on patients' quality of life (QoL). Standard treatment for patients with VLUs is the application of strong, sustained compression with bandages or stockings. This pragmatically-designed study aims to determine whether the use of a device called MIST used in combination with standard treatments can improve healing of VLUs compared to UK standard practice. It will also show whether the MIST regimen improves participants' QoL and reduces the incidence of infection. The MIST ultrasound system is a non-contact device which delivers low-frequency ultrasound through a gentle saline mist directed at a patient's wound. Patients (over 18 years old) will be invited to take part in this study if they have had a VLU for 6 weeks or more, which measures between 5 and 100 cm^2, and is not infected. Participants with diabetes must show good blood glucose control, and those with underlying chronic disorders which may affect wound healing will be excluded. All study participants will receive four weeks of standard treatment once a week at a single clinic at the Wound Healing Research Unit (WHRU), University Hospital of Wales. Patients whose wounds reduce by more than 40% during this time will be withdrawn from the study. Remaining patients will be randomly allocated to either the active group or the control group to receive a further eight weeks of treatment. Participants in the active group will receive treatment with the MIST device three times a week, as well as standard care (change of compression bandage and dressings) three times a week. The control group will receive UK standard care (which is dressing and compression bandage change at least once a week). The participants' ulcers will be measured and photographed once a week, and the wound characteristics will be assessed. Changes in participants' health related QoL will be assessed using a questionnaire at the beginning and end of the trial. Wound recurrence rates 90 days after the end of the treatment will be assessed by telephoning patients.

Official Title
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Pragmatic Randomised Controlled Trial of MIST Ultrasound Therapy Compared to UK Standard Care for the Treatment of Non-healing Venous Leg Ulcers.

Conditions
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Varicose Ulcer

Intervention / Treatment
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* Device: MIST ultrasound therapy
* Other: Standard Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Venous leg ulcers (as diagnosed by the clinician) Ankle Brachial Pressure Index (ABPI) >0.8 If multiple ulcers are present treat largest ulcer only (index ulcer) with minimum distance of 1 cm between index ulcer and any other ulcer 18 years or older Ulcer size of 5 cm^2 - 100 cm^2 (with no longest length being greater than 10 cm) at randomisation point (week 5) Mobile enough to attend clinic Index ulcer between 6 weeks and 5 years duration prior to screening date Exclusion Criteria: Uncontrolled diabetes (Hba1c ≥12%) as tested within the past 3 months Index ulcer has active infection on day of inclusion requiring use or oral or IV antibiotics Renal failure Index ulcer has exposed tendons, ligaments, muscle, or bone Osteomyelitis or cellulitis or gangrene in study limb Subjects with amputation above a trans metatarsal amputation (TMA) in the study limb Subjects with active malignancy on the study limb Index ulcer that is of arterial disease aetiology Females of child bearing potential who are not willing to use a method of highly effective contraception during the entire study Planned vascular surgery, angioplasty, or thrombolysis procedures within the study period, or 6 weeks post-operatively Planned surgical procedure during the study period for the index wound Prior skin replacement, negative pressure therapy, ultrasound therapy applied to the index wound 2 weeks before screening Oral or IV antibiotics within 48 hours of baseline measurements Growth factor therapy within previous 14 days of screening date Currently receiving or has received radiation or chemotherapy within 3 months of randomisation Pregnant or breast feeding women Subject is currently enrolled or has been enrolled in the last 30 days in another investigational device or drug trial Subject's wound would require ultrasound near an electronic implant or prosthesis Subjects lacking capacity to provide informed consent.

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard Care<br>Standard treatment for VLUs is administered once a week, i.e. compression bandaging and non-adherent dressing, with debridement if required. | Other: Standard Care<br>* Compression bandaging, non-adherent dressing, and debridement if required.<br>|
| Experimental: MIST and Standard Care<br>MIST ultrasound therapy is applied for between 3 and 12 minutes (depending on wound size) 3 times a week in combination with standard treatment for VLUs of compression bandaging and non-adherent dressing change 3 times a week, with debridement as required. | Device: MIST ultrasound therapy<br>* Low frequency, non-contact ultrasound system delivering therapeutic ultrasound via a fine saline mist to the wound bed.<br>* Other names: MIST;Other: Standard Care<br>* Compression bandaging, non-adherent dressing, and debridement if required.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change in Wound Area | Wound area is measured weekly using a digital wound imaging device. The wound boundary is digitally traced by a blinded assessor. Percentage and actual change in wound area between start of treatment (week 5) and end of treatment (week 13) is evaluated. | Week 5 to 13 | 
| Actual Change in Wound Area | Wound area is measured weekly using a digital wound imaging device. The wound boundary is digitally traced by a blinded assessor. Percentage and actual change in wound area between start of treatment (week 5) and end of treatment (week 13) is evaluated. | Week 5 to 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Overall Health Related Quality of Life (HRQoL) From Week 1 (Start) and Week 13 (Exit) | On the first and final visit participants were invited to complete a Cardiff Wound Impact Schedule (CWIS) a validated questionnaire designed to measure the impact of chronic wounds on patient health-related quality of life (HRQoL). The overall HRQoL question asks patients to rate their overall quality of life over the past week by circling a number between 0 and 10. Low scores indicate poor quality of life, and high score indicate good quality of life. Change in HRQoL was calculated by subtracting week 1 values from week 13 values. CWIS has been validated in the following paper: Price and Harding (2004) The Cardiff Wound Impact Schedule: the development of a condition specific questionnaire to assess health-related quality of life in patients with chronic wounds. International Wound Journal 1(1):10-17 | Week 1 (start) and week 13 (exit) | 
| Change in Ulcer Pain Between Week 5 (Randomisation) and Week 13 (Exit) | Pain was scored by each patient on a visual analogue score (VAS) from 0 to 100. A VAS score of 0 indicated no pain whilst a VAS score of 100 indicated worst possible pain. Change in pain scores were calculated by subtracting week 5 values from week 13 values. | Weeks 5 to 13 | 
| Incidence of Wound Infection | Median number of wound infections per patient (as demonstrated by clinical symptoms) from beginning of treatment (week 5) and end of treatment (week 13). | Weeks 5 to 13 | 
| Number of Non-serious Adverse Events in Each Group | Adverse events (AEs) were defined as any undesirable clinical occurrence in a subject whether it is thought to be related to the investigational device or not. | Week 5 to 13 | 
| Wound Recurrence Rate | Patients whose wound has healed (defined as 100% epithelialisation with no scab present) before or at the end of treatment will be asked 90 days after date of healing if their wound has remained closed. | 90 days after time of healing | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Venous Leg Ulcer, Varicose Ulcer, Chronic ulcer, Chronic wound, Ultrasound therapy, MIST device, Wound healing, Low frequency non contact ultrasound