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

Not Applicable

Completed

Conditions: Varicose Ulcer

Interventions: Other: Standard Care
Device: MIST ultrasound therapy

Registration Number: NCT01671748

Lead Sponsor: Cardiff and Vale University Health Board

Brief Summary: 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: 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 Patients whose wounds reduce by more than 40% during this time will be withdrawn from the study.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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 47

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard Care	Standard Care	Standard treatment for VLUs is administered once a week, i.e. compression bandaging and non-adherent dressing, with debridement if required.
MIST and Standard Care	MIST ultrasound therapy	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.
MIST and Standard Care	Standard Care	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.

Primary Outcome Measures

Name	Time	Method
Percentage Change in Wound Area	Week 5 to 13	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.
Actual Change in Wound Area	Week 5 to 13	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.

Secondary Outcome Measures

Name	Time	Method
Incidence of Wound Infection	Weeks 5 to 13	Median number of wound infections per patient (as demonstrated by clinical symptoms) from beginning of treatment (week 5) and end of treatment (week 13).
Change in Overall Health Related Quality of Life (HRQoL) From Week 1 (Start) and Week 13 (Exit)	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
Change in Ulcer Pain Between Week 5 (Randomisation) and Week 13 (Exit)	Weeks 5 to 13	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.
Number of Non-serious Adverse Events in Each Group	Week 5 to 13	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.
Wound Recurrence Rate	90 days after time of healing	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.