Non-contact low-frequency ultrasound therapy compared with UK standard of care for venous leg ulcers: a single-centre, assessor-blinded, randomised controlled trial.

"The authors would like to acknowledge Ruth Poole (Cedar), Kathleen Withers (Cedar) and Andrew Cleves (Cedar) for their contribution to the management of this study; Jacqueline Fletcher (Cardiff University) and Mark Kelson (Research Design and Conduct Service, Cardiff University) for their input to the design of the study protocol; and Neal Walkley (Cardiff University) and Wendy Davies (Cardiff University) for their technical assistance. This study was sponsored by Cardiff and Vale University Health Board (NHS). This study was funded through an unrestricted research grant and equipment loan from Celleration (device manufacturer); Celleration played no role in the conduct of this study or analysis and reporting of the results. Cedar is a department within the UK NHS, and it receives funding from the National Institute for Health and Care Excellence (NICE) to act as an external assessment centre. NICE was involved in initial discussions about trial design but played no further role in the conduct or analysis of the study. This is the first randomised trial on NLFU conducted in the UK and has several strengths. While the study was funded by the device manufacturer, the design, conduct and analysis has been entirely independent. Wound area measurements were performed by a single blinded assessor using a Silhouette digital wound planimetry device to reduce subjectivity and bias. Broad inclusion criteria were set to maximise generalisability, no patients withdrew following randomisation, no patients were lost to follow‐up, and best available standard treatment was applied. Patient‐reported pain and QoL data were collected using a validated tool (CWIS) to explore outcomes important to patients. Excellent patient compliance to the three times a week NLFU regime was shown with few missed visits recorded. To improve homogeneity amongst the wounds, a 4‐week run‐in period was used to standardise pre‐randomisation ulcer treatment and to remove wounds which were not deemed hard‐to‐heal. In addition, the use of ANCOVA enabled the influence of patients' baseline wound measurement of area reduction to be controlled, thus improving the statistical power. Important prognostic factors of wound size and duration were balanced between the arms by a minimisation procedure (adaptive randomisation)."