Larval therapy for leg ulcers (VenUS II): randomised controlled trialBMJ 2009; 338 doi: http://dx.doi.org/10.1136/bmj.b773 (Published 20 March 2009) Cite this as: BMJ 2009;338:b773
- Jo C Dumville, research fellow1,
- Gill Worthy, trial statistician1,
- J Martin Bland, professor of health statistics1,
- Nicky Cullum, professor, deputy head of department1,
- Christopher Dowson, professor2,
- Cynthia Iglesias, senior research fellow1,
- Joanne L Mitchell, research scientist3,
- E Andrea Nelson, reader in wound healing and director of research4,
- Marta O Soares, research fellow1,
- David J Torgerson, professor, director of York trials unit1
- on behalf of the VenUS II team
- 1Department of Health Sciences, University of York, York YO10 5DD
- 2Biological Sciences, University of Warwick
- 3Micropathology Ltd, Coventry
- 4School of Healthcare, University of Leeds
- Correspondence to: Jo C Dumville
- Accepted 14 January 2009
Objective To compare the clinical effectiveness of larval therapy with a standard debridement technique (hydrogel) for sloughy or necrotic leg ulcers.
Design Pragmatic, three armed randomised controlled trial.
Setting Community nurse led services, hospital wards, and hospital outpatient leg ulcer clinics in urban and rural settings, United Kingdom.
Participants 267 patients with at least one venous or mixed venous and arterial ulcer with at least 25% coverage of slough or necrotic tissue, and an ankle brachial pressure index of 0.6 or more.
Interventions Loose larvae, bagged larvae, and hydrogel.
Main outcome measures The primary outcome was time to healing of the largest eligible ulcer. Secondary outcomes were time to debridement, health related quality of life (SF-12), bacterial load, presence of meticillin resistant Staphylococcus aureus, adverse events, and ulcer related pain (visual analogue scale, from 0 mm for no pain to 150 mm for worst pain imaginable).
Results Time to healing was not significantly different between the loose or bagged larvae group and the hydrogel group (hazard ratio for healing using larvae v hydrogel 1.13, 95% confidence interval 0.76 to 1.68; P=0.54). Larval therapy significantly reduced the time to debridement (2.31, 1.65 to 3.2; P<0.001). Health related quality of life and change in bacterial load over time were not significantly different between the groups. 6.7% of participants had MRSA at baseline. No difference was found between larval therapy and hydrogel in their ability to eradicate MRSA by the end of the debridement phase (75% (9/12) v 50% (3/6); P=0.34), although this comparison was underpowered. Mean ulcer related pain scores were higher in either larvae group compared with hydrogel (mean difference in pain score: loose larvae v hydrogel 46.74 (95% confidence interval 32.44 to 61.04), P<0.001; bagged larvae v hydrogel 38.58 (23.46 to 53.70), P<0.001).
Conclusions Larval therapy did not improve the rate of healing of sloughy or necrotic leg ulcers or reduce bacterial load compared with hydrogel but did significantly reduce the time to debridement and increase ulcer pain.
Trial registration Current Controlled Trials ISRCTN55114812 and National Research Register N0484123692.
We thank the participants for taking part in the trial; the research nurses, tissue viability teams, district nurses, and hospital outpatient staff for recruiting participants and completing the trial documentation; the principal investigators at each site for coordinating recruitment of the participants; members of the trial steering committee (Su Mason (independent chair), Mike Campbell, and Francine Cheater); and members of the data monitoring and ethics committee (Keith Abrams (chair), Michelle Briggs, and Alun Davies) for overseeing the study.
The VenUS II collaborators (current and past) are: Una Adderley, Jacqui Ashton, Gill Bennett, JMB, Anne Marie Brown, Sue Collins, Ben Cross, NC, Val Douglas, CD, JCD, Andrea Ellis, Caroline Graham, Christine Hodgson, Gemma Hancock, Shervanthi Homer-Vanniasinkam, CI, June Jones, Nicky Kimpton, Dorothy McCaughan, Elizabeth McGinnis, Jeremy Miles, JLM, Veronica Morton, EAN, Sue O’Meara, Angie Oswald, Emily Petherick, Ann Potter, Pauline Raynor, Linda Russell, Jane Stevens, MS, Nikki Stubbs, DJT, Kath Vowden, Peter Vowden, Michael Walker, Shernaz Walton, Val Wadsworth, Margaret Wallace Judith Watson, Anne Witherow, and GW.
Contributors: JCD was trial manager between 2005 and 2008. GW and JMB designed and carried out the statistical analyses. MS and CI designed and carried out the economic analyses and contributed to the analysis of the trial. CI contributed to the design of the trial. NC was the chief investigator, led the design of the trial, chaired the Trial Management Group, and edited and approved the final draft of the report. She is guarantor. CD advised on the collection and analysis of microbiological data. JLM carried out the microbiological analysis. EAN and DJT contributed to the design and coordination of the study.
Funding: This project was funded by the UK National Institute for Health Research Health Technology Assessment Programme (project No 01/41/04). The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Department of Health. Zoobiotic supplied and distributed the loose larvae at no cost and Biomonde supplied the bagged larvae at no cost. These manufacturers had no role in the design of the trial or in the collection, analysis, and interpretation of the data.
Competing interests: None declared.
Ethical approval: This study was approved by the West Midlands multicentre research ethics committee and local ethics committees.
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