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Use of weekly, low dose, high frequency ultrasound for hard to heal venous leg ulcers: the VenUS III randomised controlled trial

BMJ 2011; 342 doi: https://doi.org/10.1136/bmj.d1092 (Published 08 March 2011) Cite this as: BMJ 2011;342:d1092
  1. Judith M Watson, research fellow1,
  2. Arthur R Kang’ombe, trial statistician1,
  3. Marta O Soares, research fellow1,
  4. Ling-Hsiang Chuang, trial health economist1,
  5. Gill Worthy, statistician2,
  6. J Martin Bland, professor of health statistics1,
  7. Cynthia Iglesias, senior research fellow1,
  8. Nicky Cullum, professor, deputy head of department 1,
  9. David Torgerson, professor, director of York Trials Unit1,
  10. E Andrea Nelson, professor of wound healing, director of research3
  11. on behalf of the VenUS III Team
  1. 1Department of Health Sciences, University of York, UK
  2. 2Kleijnen Systematic Reviews, Escrick, York, UK
  3. 3School of Healthcare, University of Leeds, Leeds LS2 9JT, UK
  1. Correspondence to: E A Nelson e.a.nelson{at}leeds.ac.uk
  • Accepted 6 January 2011

Abstract

Objective To assess the clinical effectiveness of weekly delivery of low dose, high frequency therapeutic ultrasound in conjunction with standard care for hard to heal venous leg ulcers.

Design Multicentre, pragmatic, two arm randomised controlled trial.

Setting Community and district nurse led services, community leg ulcer clinics, and hospital outpatient leg ulcer clinics in 12 urban and rural settings (11 in the United Kingdom and one in the Republic of Ireland).

Participants 337 patients with at least one venous leg ulcer of >6 months’ duration or >5 cm2 area and an ankle brachial pressure index of ≥0.8.

Interventions Weekly administration of low dose, high frequency ultrasound therapy (0.5 W/cm2, 1 MHz, pulsed pattern of 1:4) for up to 12 weeks plus standard care compared with standard care alone.

Main outcome measures Primary outcome was time to healing of the largest eligible leg ulcer. Secondary outcomes were proportion of patients healed by 12 months, percentage and absolute change in ulcer size, proportion of time participants were ulcer-free, health related quality of life, and adverse events.

Results The two groups showed no significant difference in the time to healing of the reference leg ulcer (log rank test, P=0.61). After adjustment for baseline ulcer area, baseline ulcer duration, use of compression bandaging, and study centre, there was still no evidence of a difference in time to healing (hazard ratio 0.99 (95% confidence interval 0.70 to 1.40), P=0.97). The median time to healing of the reference leg ulcer was inestimable. There was no significant difference between groups in the proportion of participants with all ulcers healed by 12 months (72/168 in ultrasound group v 78/169 in standard care group, P=0.39 for Fisher’s exact test) nor in the change in ulcer size at four weeks by treatment group (model estimate 0.05 (95% CI –0.09 to 0.19)). There was no difference in time to complete healing of all ulcers (log rank test, P=0.61), with median time to healing of 328 days (95% CI 235 to inestimable) with standard care and 365 days (224 days to inestimable) with ultrasound. There was no evidence of a difference in rates of recurrence of healed ulcers (17/31 with ultrasound v 14/31 with standard care, P=0.68 for Fisher’s exact test). There was no difference between the two groups in health related quality of life, both for the physical component score (model estimate 0.69 (–1.79 to 3.08)) and the mental component score (model estimate –0.93 (–3.30 to 1.44)), but there were significantly more adverse events in the ultrasound group (model estimate 0.30 (0.01 to 0.60)). There was a significant relation between time to ulcer healing and baseline ulcer area (hazard ratio 0.64 (0.55 to 0.75)) and baseline ulcer duration (hazard ratio 0.59 (0.50 to 0.71)), with larger and older ulcers taking longer to heal. In addition, those centres with high recruitment rates had the highest healing rates.

Conclusions Low dose, high frequency ultrasound administered weekly for 12 weeks during dressing changes in addition to standard care did not increase ulcer healing rates, affect quality of life, or reduce ulcer recurrence.

Trial registration ISRCTN21175670 and National Research Register N0484162339

Footnotes

  • We thank the patients who took part in this trial; the research nurses, tissue viability teams, district nurses, and hospital outpatient staff who recruited patients and completed the trial documentation; principal investigators at each site; members of the trial steering committee (S Homer-Vanniasinkam (chair 2006), Su Mason (member 2006, then chair 2007–8), Kevin Burnand, Denise Howell, Timothy Rowlands, Nikki Stubbs); and members of the data monitoring and ethics committee (Robin Prescott (chair), Andrew Bradbury, Brenda King) who oversaw the study. We also thank Bernie Boyle, Susan Bradley, Melanie Burrows, Margaret Crookes, Joanne Dakin, Patricia Davies, Erica Denton, Mary Doherty, Sarah Fiori, Gemma Hancock, June Jones, Peter Jones, Denise Nightingale, Lesley Marland, Jeanette Marshall, Jane Mayes, Jane Megson, Sue Merryweather, Carol Muir, Pam Ross, Rebecca Stubbs, Debra Vickery, Victoria Warner, Shirley Williams, and Lindsey Worstenholme for recruiting participants into the study; Una Adderley, Gemma Hancock, and Susan O’Meara, who undertook the blinded outcomes assessment of ulcer photographs; and Mei-See Man, who carried out the ulcer tracing measurements.

  • The VenUS III collaborators (current and past) are Una Adderley, Paul Allcoat, Jacqui Ashton, JMB, Annemarie Brown, Sue Collins, L-HC, Ben Cross, NC, Carol Dealey, Jo Dumville, Kate Flemming, Liz Holey, CI, ARK, Linda McDermott-Scales, Janet McGowan, EAN, Angie Oswald, Sarah Pankhurst, Stephen Pye, Elizabeth McGinnis, MOS, Gerben ter Riet, DT, Kath Vowden, Peter Vowden, Michael Walker, Shernaz Walton, Val Wadsworth, JMW, GW, and Anne Witherow.

  • Contributors: EAN was the chief investigator, chaired the trial management group, and edited and approved the final draft of the paper. JMW was the trial coordinator and drafted the paper. GW and JMB designed the clinical analysis. JMB oversaw the conduct of the analysis. ARK conducted the clinical analysis. MOS contributed to the trial management group, designed the economic analyses, and oversaw the conduct of the analysis. L-HC undertook the economic analysis. CI participated in the design and conduct of the study. NC and DT contributed to the study design and coordination and commented on drafts of the paper. EAN is the guarantor of the paper.

  • Funding: This project was funded by the UK National Institute for Health Research (NIHR) Health Technology Assessment Programme (project No 02/37/03), and it will be published in full in the journal Health Technology Assessment. The NIHR had no role in the data collection, statistical analysis, or writing of this article or the decision to submit for publication. The views and opinions expressed herein are those of the authors and do not necessarily reflect those of the Department of Health. EMS Physio supplied the SoLo Therasonic 355 ultrasound machines at a discounted price, but had no role in the design of the trial or in the collection, analysis, and interpretation of the data.

  • Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: JW, AK, L-HC and EAN all received proportions of their salaries from this grant in order to conduct the study. All other authors declare no support from any organisation for the submitted work.

  • Ethical approval: The study was approved by York Multicentre Research Ethics Committee (MREC), local research ethics committees, and research and development departments.

  • Data sharing: No additional data available

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