{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T14:18:24Z","timestamp":1776867504968,"version":"3.51.2"},"reference-count":33,"publisher":"BMJ","issue":"4","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"unspecified","delay-in-days":21,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Mayo Clinic Critical Care Independent Multidisciplinary Program (IMP) Research Subcommittee"},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["1R61HL177037"],"award-info":[{"award-number":["1R61HL177037"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,3,31]]},"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Sepsis is a global health priority with nearly 50\u2009million cases annually. Cardiovascular dysfunction is common, frequently manifesting as hypotension that persists despite fluid resuscitation. Most affected patients require the use of intravenous (IV) vasoactive agents, typically necessitating intensive care unit (ICU)-level monitoring, invasive interventions and contributing substantially to healthcare costs. Midodrine, an oral alpha-1 agonist approved for orthostatic hypotension, has increasingly been used off-label as a vasopressor-sparing (reducing IV vasopressor use) strategy in sepsis, despite limited and inconsistent evidence. This pragmatic, randomised, open-label trial evaluates the efficacy and safety of midodrine in patients with sepsis-associated hypotension. We hypothesise that, compared with standard care, midodrine administration will reduce the duration of IV vasopressor use.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>A total of 308 adult patients with sepsis-associated hypotension will be enrolled (154 per arm). The intervention group will, in addition to standard of care, receive enteral midodrine 10\u2009mg three times daily. Outcomes will be ascertained pragmatically via electronic health record-based data retrieval and adjudicated by research coordinators blinded to treatment assignment. The primary outcome is time alive and off IV vasopressors in the first 28 days (in hours) after randomisation. Secondary outcomes include cumulative vasopressor exposure; use and duration of central venous access; cumulative fluid balance over the first 48 hours and up to 7\u2009days of ICU stay; ICU and hospital length of stay; and ICU-, hospital-, and organ support-free days through day 28. Safety outcomes include adverse events potentially attributable to midodrine during hospitalisation including acute kidney injury. Primary analyses will follow an intention-to-treat framework, including all randomised participants according to their assigned treatment groups. Primary and secondary outcomes will be compared using a van Elteren test stratified by randomisation factors. A predefined secondary Bayesian analysis of the primary outcome will provide complementary estimates of treatment effect. Safety outcomes will be summarised descriptively without formal between-arm hypothesis testing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The Mayo Clinic Institutional Review Board approved this protocol and required written informed consent from all participants (IRB# 24\u20130\u200900\u2009121). Findings will be disseminated through peer-reviewed publications and international conference presentations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06319248\">NCT06319248<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2026-117846","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T13:30:36Z","timestamp":1776864636000},"page":"e117846","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Midodrine for Sepsis Treatment and Early Vasopressor Weaning (MID-STEP): protocol for a pragmatic randomised clinical trial"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct06319248","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06319248","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1891-2118","authenticated-orcid":false,"given":"Aysun","family":"Tekin","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Halpern","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diksha","family":"Gowda","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vikas","family":"Bansal","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Schuchard","sequence":"additional","affiliation":[{"name":"Pulmonary and Critical Care Research Unit, Mayo Clinic, Rochester, Minnesota, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anes","family":"Joguncic","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Public Health Institute of Canton of Sarajevo, Sarajevo, Bosnia and Herzegovina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip","family":"Schulte","sequence":"additional","affiliation":[{"name":"Division of Clinical Trials and Biostatistics, Department of Quantitative Health 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