Trial Outcomes & Findings for MIST Ultrasound Therapy Compared to United Kingdom Standard Care for the Treatment of Non-healing Venous Leg Ulcers (NCT NCT01671748)

NCT ID: NCT01671748

Last Updated: 2015-08-26

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

47 participants

Primary outcome timeframe

Week 5 to 13

Results posted on

2015-08-26

Participant Flow

Study procedures took place in a single dedicated unit specialising in wound healing research, between August 2012 and November 2013.

All enrolled patients received 4 weeks of SOC prior to random allocation (run-in phase). Patients whose wounds reduced by \>40% in the first 4 weeks were withdrawn and did not progress to random allocation.

Participant milestones

Participant milestones
Measure
Standard of Care
Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.
NLFU and Standard of Care
Non-contact low frequency ultrasound (NLFU) using 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.
4 Week run-in Phase
STARTED
47
0
4 Week run-in Phase
COMPLETED
36
0
4 Week run-in Phase
NOT COMPLETED
11
0
12 Week Treatment Phase
STARTED
19
17
12 Week Treatment Phase
COMPLETED
19
17
12 Week Treatment Phase
NOT COMPLETED
0
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Standard of Care
Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.
NLFU and Standard of Care
Non-contact low frequency ultrasound (NLFU) using 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.
4 Week run-in Phase
Withdrawal by Subject
1
0
4 Week run-in Phase
Adverse Event
1
0
4 Week run-in Phase
Not eligible
9
0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Standard of Care
n=19 Participants
Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.
NLFU and Standard of Care
n=17 Participants
Non-contact low frequency ultrasound (NLFU) using 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.
Total
n=36 Participants
Total of all reporting groups
Age, Continuous
68.2 years
STANDARD_DEVIATION 12.2 • n=5 Participants
70.5 years
STANDARD_DEVIATION 12.7 • n=7 Participants
69 years
STANDARD_DEVIATION 12.0 • n=5 Participants
Sex: Female, Male
Female
12 Participants
n=5 Participants
9 Participants
n=7 Participants
21 Participants
n=5 Participants
Sex: Female, Male
Male
7 Participants
n=5 Participants
8 Participants
n=7 Participants
15 Participants
n=5 Participants
Region of Enrollment
United Kingdom
19 participants
n=5 Participants
17 participants
n=7 Participants
36 participants
n=5 Participants
History of leg ulceration (months)
94.7 months
STANDARD_DEVIATION 83.2 • n=5 Participants
109.7 months
STANDARD_DEVIATION 112.2 • n=7 Participants
101.8 months
STANDARD_DEVIATION 96.8 • n=5 Participants
Index ulcer duration (months)
22.3 months
STANDARD_DEVIATION 18.5 • n=5 Participants
15.7 months
STANDARD_DEVIATION 12.0 • n=7 Participants
19 months
STANDARD_DEVIATION 16 • n=5 Participants
Wound size at enrolment (cm^2)
19.4 cm^2
STANDARD_DEVIATION 14.9 • n=5 Participants
15.9 cm^2
STANDARD_DEVIATION 9.9 • n=7 Participants
17.8 cm^2
STANDARD_DEVIATION 12.7 • n=5 Participants
Change in wound size during run-in phase (%)
-13.0 percentage change in wound area
STANDARD_DEVIATION 25.2 • n=5 Participants
-10.9 percentage change in wound area
STANDARD_DEVIATION 23.9 • n=7 Participants
-12.0 percentage change in wound area
STANDARD_DEVIATION 24.3 • n=5 Participants

PRIMARY outcome

Timeframe: Week 5 to 13

Population: All patients included in the analysis; Intention to treat (ITT); Values have been adjusted for the influence of the covariate (wound area at the start of treatment)

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.

Outcome measures

Outcome measures
Measure
Standard of Care
n=19 Participants
Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.
NLFU and Standard of Care
n=17 Participants
Non-contact low frequency ultrasound (NLFU) using 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.
Percentage Change in Wound Area
-39.2 percentage change in wound area
Standard Deviation 38.0
-46.6 percentage change in wound area
Standard Deviation 38.1

PRIMARY outcome

Timeframe: Week 5 to 13

Population: As previous

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.

Outcome measures

Outcome measures
Measure
Standard of Care
n=19 Participants
Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.
NLFU and Standard of Care
n=17 Participants
Non-contact low frequency ultrasound (NLFU) using 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.
Actual Change in Wound Area
-5.3 cm2
Standard Deviation 5.5
-6.2 cm2
Standard Deviation 5.5

SECONDARY outcome

Timeframe: Week 1 (start) and week 13 (exit)

Population: All patients were analysed by ITT

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

Outcome measures

Outcome measures
Measure
Standard of Care
n=19 Participants
Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.
NLFU and Standard of Care
n=17 Participants
Non-contact low frequency ultrasound (NLFU) using 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.
Change in Overall Health Related Quality of Life (HRQoL) From Week 1 (Start) and Week 13 (Exit)
0 units on a scale
Interval -1.0 to 1.0
-1 units on a scale
Interval -2.0 to 2.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Standard of Care
n=19 Participants
Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.
NLFU and Standard of Care
n=17 Participants
Non-contact low frequency ultrasound (NLFU) using 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.
Change in Ulcer Pain Between Week 5 (Randomisation) and Week 13 (Exit)
-5.27 scores on a scale
Standard Deviation 14.84
-14.35 scores on a scale
Standard Deviation 14.85

SECONDARY outcome

Timeframe: Weeks 5 to 13

Population: All patients included; ITT.

Median number of wound infections per patient (as demonstrated by clinical symptoms) from beginning of treatment (week 5) and end of treatment (week 13).

Outcome measures

Outcome measures
Measure
Standard of Care
n=19 Participants
Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.
NLFU and Standard of Care
n=17 Participants
Non-contact low frequency ultrasound (NLFU) using 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.
Incidence of Wound Infection
2 Number of infections per patient
Interval 1.0 to 3.0
2 Number of infections per patient
Interval 0.0 to 3.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
Standard of Care
n=19 Participants
Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.
NLFU and Standard of Care
n=17 Participants
Non-contact low frequency ultrasound (NLFU) using 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.
Number of Non-serious Adverse Events in Each Group
70 Number of non-serious AEs
59 Number of non-serious AEs

SECONDARY outcome

Timeframe: 90 days after time of healing

Population: Three patients healed during the study period (one NLFU+SOC patient healed after 7 weeks and one after 8 weeks of NLFU+SOC treatment, and one patient who received standard care alone healed after 4 weeks). All three of these patients remained healed 90 days after the end of their study treatment.

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.

Outcome measures

Outcome measures
Measure
Standard of Care
n=1 Participants
Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.
NLFU and Standard of Care
n=2 Participants
Non-contact low frequency ultrasound (NLFU) using 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.
Wound Recurrence Rate
1 Number of wounds remained healed
2 Number of wounds remained healed

Adverse Events

Standard of Care

Serious events: 0 serious events
Other events: 19 other events
Deaths: 0 deaths

NLFU and Standard of Care

Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Standard of Care
n=19 participants at risk
Standard of Care (SOC) was compression bandaging and non-adherent dressing at least once a week (more frequent visits if clinically necessary). Debridement was performed as required.
NLFU and Standard of Care
n=17 participants at risk
Non-contact low frequency ultrasound (NLFU) using 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.
General disorders
All adverse events
100.0%
19/19 • Study period of 13 weeks
Any undesirable clinical occurrence in a subject whether it is thought to be related to the NLFU or not. All subjects experiencing AEs were monitored until symptoms subside or until there is a satisfactory explanation for the changes observed. The nature of venous leg ulcers meant that AEs were common in both the SOC and NLFU groups
88.2%
15/17 • Study period of 13 weeks
Any undesirable clinical occurrence in a subject whether it is thought to be related to the NLFU or not. All subjects experiencing AEs were monitored until symptoms subside or until there is a satisfactory explanation for the changes observed. The nature of venous leg ulcers meant that AEs were common in both the SOC and NLFU groups

Additional Information

Dr Judith White

Cardiff and Vale University Health Board

Phone: 02920744771

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place