{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:41:37Z","timestamp":1792719697217,"version":"4.5.0"},"reference-count":19,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T00:00:00Z","timestamp":1685059200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T00:00:00Z","timestamp":1685059200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000664","name":"Health Technology Assessment Programme","doi-asserted-by":"publisher","award":["NIHR128625"],"award-info":[{"award-number":["NIHR128625"]}],"id":[{"id":"10.13039\/501100000664","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Trials"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Venous leg ulcer(s) are common, recurring, open wounds on the lower leg, resulting from diseased or damaged leg veins impairing blood flow. Wound healing is the primary treatment aim for venous leg ulceration, alongside the management of pain, wound exudate and infection.<\/jats:p>\n                <jats:p>Full (high) compression therapy delivering 40\u00a0mmHg of pressure at the ankle is the recommended first-line treatment for venous leg ulcers. There are several different forms of compression therapy available including wraps, two-layer hosiery, and two-layer or four-layer bandages.<\/jats:p>\n                <jats:p>There is good evidence for the clinical and cost-effectiveness of four-layer bandage and two-layer hosiery but more limited evidence for other treatments (two-layer bandage and compression wraps). Robust evidence is required to compare clinical and cost-effectiveness of these and to investigate which is the best compression treatment for reducing time to healing of venous leg ulcers whilst offering value for money. VenUS 6 will therefore investigate the clinical and cost-effectiveness of evidence-based compression, two-layer bandage and compression wraps for time to healing of venous leg ulcers.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>VenUS 6 is a pragmatic, multi-centre, three-arm, parallel-group, randomised controlled trial. Adult patients with a venous leg ulcer will be randomised to receive (1) compression wraps, (2) two-layer bandage or (3) evidence-based compression (two-layer hosiery or four-layer bandage).<\/jats:p>\n                <jats:p>Participants will be followed up for between 4 and 12\u00a0months. The primary outcome will be time to healing (full epithelial cover in the absence of a scab) in days since randomisation. Secondary outcomes will include key clinical events (e.g. healing of the reference leg, ulcer recurrence, ulcer\/skin deterioration, amputation, admission\/discharge, surgery to close\/remove incompetent superficial veins, infection or death), treatment changes, adherence and ease of use, ulcer related pain, health-related quality of life and resource use.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Discussion<\/jats:title>\n                <jats:p>VenUS 6 will provide robust evidence on the clinical and cost-effectiveness of the different forms of compression therapies for venous leg ulceration.<\/jats:p>\n                <jats:p>VenUS 6 opened to recruitment in January 2021 and is currently recruiting across 30 participating centres.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Trial registration<\/jats:title>\n                <jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/doi.org\/10.1186\/ISRCTN67321719\">ISRCTN67321719<\/jats:ext-link>. Prospectively registered on 14 September 2020<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13063-023-07349-2","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T14:02:21Z","timestamp":1685109741000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A randomised controlled trial of compression therapies for the treatment of venous leg ulcers (VenUS 6): study protocol for a pragmatic, multicentre, parallel-group, three-arm randomised controlled trial"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0512-4339","authenticated-orcid":false,"given":"C. E.","family":"Arundel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Welch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Saramago","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"U.","family":"Adderley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Atkinson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Chetter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Cullum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T.","family":"Davill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Griffiths","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Hewitt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Hirst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Kletter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Mullings","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Roberts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B.","family":"Smart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Soares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Stather","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Strachan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Stubbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. J.","family":"Torgerson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Watson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Zahra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Dumville","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,5,26]]},"reference":[{"key":"7349_CR1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD000265.pub3","author":"S O\u2019Meara","year":"2012","unstructured":"O\u2019Meara S, Cullum N, Nelson EA, Dumville JC. Compression for venous leg ulcers. Cochrane Database Syst Rev. 2012. https:\/\/doi.org\/10.1002\/14651858.CD000265.pub3.","journal-title":"Cochrane Database Syst Rev"},{"key":"7349_CR2","doi-asserted-by":"publisher","first-page":"2105","DOI":"10.1056\/NEJMoa1801214","volume":"378","author":"M Gohel","year":"2018","unstructured":"Gohel M, Heatley F, Liu X, Bradbury A, Bulbulia R, Cullum N, et al. A randomized trial of early endovenous ablation in venous ulceration. N Engl J Med. 2018;378:2105\u201314.","journal-title":"N Engl J Med"},{"key":"7349_CR3","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1002\/bjs.11082","volume":"106","author":"D Epstein","year":"2019","unstructured":"Epstein D, Gohel M, Heatley F, et al. Cost-effectiveness analysis of a randomized clinical trial of early versus deferred endovenous ablation of superficial venous reflux in patients with venous ulceration. Br J Surg. 2019;106:555\u201362.","journal-title":"Br J Surg"},{"key":"7349_CR4","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/1471-2288-14-105","volume":"14","author":"P Saramago","year":"2014","unstructured":"Saramago P, Chuang LH, Soares MO. Network meta-analysis of (individual patient) time to event data alongside (aggregate) count data. BMC Med Res Methodol. 2014;14:105. https:\/\/doi.org\/10.1186\/1471-2288-14-105.","journal-title":"BMC Med Res Methodol"},{"issue":"29","key":"7349_CR5","doi-asserted-by":"publisher","first-page":"iii, 1-105","DOI":"10.3310\/hta8290","volume":"8","author":"C Iglesias","year":"2004","unstructured":"Iglesias C, Nelson E, Cullum N, Torgerson DJ, the VenUS team. VenUS I: a randomised controlled trial of two types of bandage for treating venous leg ulcers. Health Technol Assess. 2004;8(29):iii, 1\u2013105. https:\/\/doi.org\/10.3310\/hta8290.","journal-title":"Health Technol Assess"},{"key":"7349_CR6","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1002\/bjs.4754","volume":"91","author":"E Nelson","year":"2004","unstructured":"Nelson E, Iglesias C, Cullum N, et al. Randomized clinical trial of four-layer and short-stretch compression bandages for venous leg ulcers (VenUS I). Br J Surg. 2004;91:1292\u20139. https:\/\/doi.org\/10.1002\/bjs.4754.","journal-title":"Br J Surg"},{"key":"7349_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3310\/hta18570","volume":"18","author":"RLGR Ashby","year":"2014","unstructured":"Ashby RLGR, Ali S, Saramago P, Chuang LH, Adderley U, et al. VenUS IV (Venous leg Ulcer Study IV) - compression hosiery compared with compression bandaging in the treatment of venous leg ulcers: a randomised controlled trial, mixed-treatment comparison and decision-analytic model. Health Technol Assess. 2014;18:1\u2013293.","journal-title":"Health Technol Assess"},{"key":"7349_CR8","doi-asserted-by":"publisher","first-page":"553","DOI":"10.12968\/jowc.2012.21.11.553","volume":"21","author":"I Lazareth","year":"2012","unstructured":"Lazareth I, Moffatt C, Dissemond J, et al. Efficacy of two compression systems in the management of VLUs: results of a European RCT. J Wound Care. 2012;21:553\u201365. https:\/\/doi.org\/10.12968\/jowc.2012.21.11.553.","journal-title":"J Wound Care"},{"key":"7349_CR9","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1111\/j.1742-481X.2008.00487.x","volume":"5","author":"CJ Moffatt","year":"2008","unstructured":"Moffatt CJ, Edwards L, Collier M, et al. A randomised controlled 8-week crossover clinical evaluation of the 3M Coban 2 Layer Compression System versus Profore to evaluate the product performance in patients with venous leg ulcers. Int Wound J. 2008;5:267\u201379.","journal-title":"Int Wound J"},{"key":"7349_CR10","doi-asserted-by":"publisher","first-page":"793","DOI":"10.5114\/aoms.2010.17097","volume":"6","author":"MT Szewczyk","year":"2010","unstructured":"Szewczyk MT, Jawie\u0144 A, Cierzniakowska K, et al. Comparison of the effectiveness of compression stockings and layer compression systems in venous ulceration treatment. Arch Med Sci. 2010;6:793\u20139.","journal-title":"Arch Med Sci"},{"key":"7349_CR11","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1016\/j.jvs.2005.08.015","volume":"42","author":"S Blecken","year":"2005","unstructured":"Blecken S, Villavicencio JL, Kao TC. Comparison of elastic versus nonelastic compression in bilateral venous ulcers: a randomized trial. J Vasc Surg. 2005;42:1150\u20135.","journal-title":"J Vasc Surg"},{"key":"7349_CR12","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1177\/0268355519858439","volume":"35","author":"G Mosti","year":"2020","unstructured":"Mosti G, Mancini S, Bruni S, et al. Adjustable compression wrap devices are cheaper and more effective than inelastic bandages for venous leg ulcer healing. A multicentric Italian randomized clinical experience. Phlebology. 2020;35:124\u201333.","journal-title":"Phlebology"},{"key":"7349_CR13","doi-asserted-by":"publisher","first-page":"e1119","DOI":"10.1136\/bmj.e1119","volume":"37","author":"ATA Hrobjartsson","year":"2012","unstructured":"Hrobjartsson ATA, Emanuelsson F, Tendal B, Hilden J, Boutron I, et al. Observer bias in randomised clinical trials with binary outcomes: systematic review of trials with both blinded and non-blinded outcome assessors. BMJ. 2012;37:e1119.","journal-title":"BMJ"},{"key":"7349_CR14","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1186\/s12872-015-0080-7","volume":"15","author":"JM Bland","year":"2015","unstructured":"Bland JM, Dumville JC, Ashby RL, et al. Validation of the VEINES-QOL quality of life instrument in venous leg ulcers: repeatability and validity study embedded in a randomised clinical trial. BMC Cardiovasc Disord. 2015;15:85. https:\/\/doi.org\/10.1186\/s12872-015-0080-7.","journal-title":"BMC Cardiovasc Disord"},{"key":"7349_CR15","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/0168-8510(90)90421-9","volume":"16","author":"The EuroQol Group","year":"1990","unstructured":"The EuroQol Group. EuroQol-a new facility for the measurement of health-related quality of life. Health Policy. 1990;16:199\u2013208.","journal-title":"Health Policy"},{"key":"7349_CR16","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-018-2535-5","author":"S Treweek","year":"2018","unstructured":"Treweek S, Bevan S, Bower P, et al. Trial forge guidance 1: what is a study within a trial (SWAT)? Trials. 2018. https:\/\/doi.org\/10.1186\/s13063-018-2535-5.","journal-title":"Trials"},{"key":"7349_CR17","doi-asserted-by":"publisher","unstructured":"Edwards P, Roberts I, Clarke M, et al. Methods to increase response rates to postal questionnaires. Cochrane Database Syst Rev. 2007(2): MR000008. https:\/\/doi.org\/10.1002\/14651858.MR000008.pub4.","DOI":"10.1002\/14651858.MR000008.pub4"},{"key":"7349_CR18","doi-asserted-by":"publisher","first-page":"e052953","DOI":"10.1136\/bmjopen-2021-052953","volume":"12","author":"TP Clark","year":"2022","unstructured":"Clark TP, Kahan BC, Phillips A, et al. Estimands: bringing clarity and focus to research questions in clinical trials. BMJ Open. 2022;12:e052953. https:\/\/doi.org\/10.1136\/bmjopen-2021-052953.","journal-title":"BMJ Open"},{"key":"7349_CR19","doi-asserted-by":"publisher","DOI":"10.22024\/UniKent\/01.02.70995","volume-title":"Unit costs of health and social care 2018","author":"L Curtis","year":"2018","unstructured":"Curtis L, Burns A. Unit costs of health and social care 2018. Canterbury: Personal Social Services Research Unit, University of Kent; 2018. https:\/\/doi.org\/10.22024\/UniKent\/01.02.70995."}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-023-07349-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-023-07349-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-023-07349-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T14:03:47Z","timestamp":1685109827000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-023-07349-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,26]]},"references-count":19,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["7349"],"URL":"https:\/\/doi.org\/10.1186\/s13063-023-07349-2","relation":{},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,26]]},"assertion":[{"value":"31 March 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 May 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethical approval for this trial has been granted by the West of Scotland 4 Research Ethics Committee\u2014reference 20-WS-0121 (approval dated: 15.09.2020). Participants are required to provide informed consent prior to participation.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate {24}"}},{"value":"Not applicable\u2014no identifying images or other personal or clinical details of participants are presented here or will be presented in reports of the trial results. Informed consent materials are attached as .","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication {32}"}},{"value":"During the study, CH was a member of NIHR CTU Standing advisory committee, NIHR HTA post-funding committee teleconference, NIHR HTA Funding Committee Policy Group (formerly CSG), NIHR HTA commissioning committee and Deputy Chair of the NIHR HTA commissioning committee.All other members of the writing committee declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests {28}"}}],"article-number":"357"}}