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Nevertheless, the use of these techniques in clinical practice is variable and its application worldwide remains limited by its requirement for the use of an intracoronary pressure wire and prolonged procedure time. Recently, angiography-based wire-free techniques to estimate fractional flow reserve (FFR) values have been introduced. These developments may translate towards more physiology-guided intervention bearing the potential to improve clinical outcomes in patients with stable coronary artery disease (CAD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The LIPSIA-STRATEGY trial is a randomized controlled, investigator-initiated, multicenter, open-label study. A total of 1054 eligible patients will be randomized 1:1 to coronary revascularization based on angiography-derived vessel fractional flow reserve (vFFR) or revascularization based on FFR obtained by pressure wire measurements. The major inclusion criterion is the presence of visually assessed intermediate coronary artery stenoses in one or more native major epicardial coronary arteries in the setting of stable angina or an acute coronary syndrome (ACS). In patients with an ACS, only non-culprit vessels will be considered for inclusion. The primary endpoint is the occurrence of major adverse cardiovascular events (MACE) during the first year after randomization.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>The LIPSIA-STRATEGY trial will be the first to compare angiography-derived vFFR with invasive FFR with respect to clinical outcomes in patients with intermediate coronary lesions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT03497637. Registered 2018\u201304-13.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-026-09652-0","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T05:07:53Z","timestamp":1775020073000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Non-invasive vessel fractional flow reserve versus fractional flow reserve guidance to revascularize intermediate coronary stenosis (LIPSIA-STRATEGY) trial: study protocol for a randomized controlled trial"],"prefix":"10.1186","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7788-6004","authenticated-orcid":false,"given":"Nicolas","family":"Majunke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Desch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Kister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Buske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"P\u00f6ss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Josef","family":"Feistritzer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Erbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine","family":"H\u00f6sler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine","family":"Wolff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Schneider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taoufik","family":"Ouarrak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Woitek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karsten","family":"Lenk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Nef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oliver","family":"D\u00f6rr","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Sossalla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Achenbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Marwan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Barlagiannis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Haude","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir Abbas","family":"Mahabadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tienush","family":"Rassaf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holger","family":"Thiele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"9652_CR1","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1016\/j.jcin.2012.07.007","volume":"5","author":"SJ Park","year":"2012","unstructured":"Park SJ, Kang SJ, Ahn JM, Shim EB, Kim YT, Yun SC, et al. 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Before start of this clinical trial, the actual study protocol including all other forms required will be presented by the coordinating investigator for approval to the local ethical committee at the University of Leipzig. Any changes required by the ethical committee will be followed for the appropriate conduct of the trial. The clinical trial can only be performed after ethical approval. All participating patients will provide written informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate {29}"}},{"value":"Not applicable. This manuscript does not contain personal or clinical details of participants.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication {32}"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests {28}"}}],"article-number":"287"}}