Intended for healthcare professionals

CCBYNC Open access

Cryotherapy versus salicylic acid for the treatment of plantar warts (verrucae): a randomised controlled trial

BMJ 2011; 342 doi: (Published 07 June 2011) Cite this as: BMJ 2011;342:d3271
  1. Sarah Cockayne, research fellow1,
  2. Catherine Hewitt, statistician1,
  3. Kate Hicks, research fellow1,
  4. Shalmini Jayakody, trial statistician1,
  5. Arthur Ricky Kang’ombe, trial statistician1,
  6. Eugena Stamuli, trial health economist1,
  7. Gwen Turner, trials support officer1,
  8. Kim Thomas, associate professor2,
  9. Mike Curran, senior lecturer podiatry3,
  10. Gary Denby, research assistant3,
  11. Farina Hashmi, senior lecturer4,
  12. Caroline McIntosh, senior lecturer5,
  13. Nichola McLarnon, senior lecturer6,
  14. David Torgerson, professor, director of York Trials Unit1,
  15. Ian Watt, professor, primary care17
  16. on behalf of the EVerT Team
  1. 1Department of Health Sciences, York Trials Unit, University of York, York YO10 5DD, UK
  2. 2Centre of Evidence Based Dermatology, University of Nottingham, UK
  3. 3School of Health, University of Northampton, UK
  4. 4University of Brighton, School of Health Professions, UK
  5. 5The National University of Ireland, Galway, Discipline of Podiatry, Galway, Ireland
  6. 6Glasgow Caledonian University, School of Health and Social Care, UK
  7. 7Hull York Medical School, UK
  1. Corresponding to: S Cockayne sarah.cockayne{at}
  • Accepted 20 April 2011


Objective To compare the clinical effectiveness of cryotherapy versus salicylic acid for the treatment of plantar warts.

Design A multicentre, open, two arm randomised controlled trial.

Setting University podiatry school clinics, NHS podiatry clinics, and primary care in England, Scotland, and Ireland.

Participants 240 patients aged 12 years and over, with a plantar wart that in the opinion of the healthcare professional was suitable for treatment with both cryotherapy and salicylic acid.

Interventions Cryotherapy with liquid nitrogen delivered by a healthcare professional, up to four treatments two to three weeks apart. Patient self treatment with 50% salicylic acid (Verrugon) daily up to a maximum of eight weeks.

Main outcome measures Complete clearance of all plantar warts at 12 weeks. Secondary outcomes were (a) complete clearance of all plantar warts at 12 weeks controlling for age, whether the wart had been treated previously, and type of wart, (b) patient self reported clearance of plantar warts at six months, (c) time to clearance of plantar wart, (d) number of plantar warts at 12 weeks, and (e) patient satisfaction with the treatment.

Results There was no evidence of a difference between the salicylic acid and cryotherapy groups in the proportions of participants with complete clearance of all plantar warts at 12 weeks (17/119 (14%) v 15/110 (14%), difference 0.65% (95% CI –8.33 to 9.63), P=0.89). The results did not change when the analysis was repeated but with adjustment for age, whether the wart had been treated previously, and type of plantar wart or for patients’ preferences at baseline. There was no evidence of a difference between the salicylic acid and cryotherapy groups in self reported clearance of plantar warts at six months (29/95 (31%) v 33/98 (34%), difference –3.15% (–16.31 to 10.02), P=0.64) or in time to clearance (hazard ratio 0.80 (95% CI 0.51 to 1.25), P=0.33). There was also no evidence of a difference in the number of plantar warts at 12 weeks (incident rate ratio 1.08 (0.81 to 1.43), P=0.62).

Conclusions Salicylic acid and the cryotherapy were equally effective for clearance of plantar warts.

Trial registration Current Controlled Trials ISRCTN18994246, National Research Register N0484189151.


  • We thank the participants for taking part in the trial; the podiatrists, general practitioners, and practice nurses for recruiting participants to the study and completing the trial documentation; the principal investigators at each site for coordinating participant recruitment; members of the trial steering committee (Sam Gibbs (independent chair), Jill Mollison, Elaine Thomas, and Wesley Vernon); and members of the data monitoring and ethics committee (Anne-Maree Keenan (independent chair), Matthew Hankins, and Katharine Speaks for overseeing the study. We also thank Jill Hall, Jude Watson, and Farina Hashmi, who undertook the blinded outcome assessment of the digital photographs and Gill Worthy for providing statistical advice.

  • The EVerT collaborators (current and past) are Peter Arthur, Lucy Bellas, Beverly Brown, Lynne Bryan, Amanda Clark, Andrew Clarke, Michael Concannon, Beryl Cooling, Dawn Curruthers, Chris Davies, Gary Denby, Sean Dinneen, Diane Exley, Lisa Farndon, Simon Gazeley, Elizabeth Green, Stephanie Haughy, Julia Haswell, Christine Hearmon, Christine Howell, Arthur Kang’ombe, Jamil Karolia, Susan Kitchener, Phillip LeDune, Susan Lightfoot, Maria Madigan, Julie Mandehzadeh, Rina Miah, Caroline McIntosh, Christine Northern, Frances Price, Julie Poland, Ilan Rajap, Jayne Robinson, Julie Robinson, Raymond Skinner, Deborah Turner, Susan Walton, Linda White, Catriona Williams, who were members of the research team at each site and recruited participants to the study; Fiona Aitken and Helen Hill from the Medicines for Children Local Research Network; and Kate Biscomb and Kate Wyer from the Primary Care Research Network.

  • Contributors: DT and Jill Hall wrote the original protocol. SC, MC, FH, NM, DT, and KT were co-applicants on the application to Health Technology Assessment Programme and refined the protocol. SC acts as guarantor for the paper. DT and IW were chief investigators and oversaw the study. SC and KH were the trial coordinators, and GT was the trial support officer. Gill Worthy, SJ, and CH designed the clinical analysis. CH oversaw the conduct of the analysis. SJ and ARK conducted the clinical analysis. ES designed and undertook the economic analysis. The writing team consisted of SC, KH, CH, ES, KT, and ARK, who drafted the report. GD, CM, FH, SJ, DT, IW, and GT commented on the report.

  • Funding: This project was funded by the UK National Institute for Health Research, Health Technology Assessment Programme (project No 05/513/02) and will be published in full in the journal Health Technology Assessment. The views and opinions expressed are those of the authors and do not necessarily reflect those of the Department of Health. William Ransom and Son supplied the 50% salicylic acid (Verrugon) at no cost, and BOC provided one site with liquid nitrogen storage equipment at reduced cost. These manufacturers had no role in the design of the trial or in the collection, analysis, and interpretation of data.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at (available on request from the corresponding author) and declare: SC, KH, SJ, GT, KT, MC, FH, NM, and DT received proportions of their salaries from the Health Technology Assessment grant in order to conduct the study; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: This study was approved by Trent Multicentre Research Ethics Committee, Galway Research Ethics Committee, and local ethics committees, Medicines and Healthcare products Regulatory Agency, Irish Medicines Board, and local research and development trusts.

  • Data sharing: No additional data available.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license. See: and

View Full Text