{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T06:15:31Z","timestamp":1792822531138,"version":"4.5.0"},"reference-count":33,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T00:00:00Z","timestamp":1761523200000},"content-version":"unspecified","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"French Ministry of Health","award":["PHRC-N-18-0798)"],"award-info":[{"award-number":["PHRC-N-18-0798)"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,9,25]]},"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Subarachnoid haemorrhage (SAH) is relatively frequent, accounting for 5% of strokes and affects a young population. Arterial vasospasm is a frequent complication of SAH, with an estimated incidence as high as 70%. Vasospasm is responsible for cerebral ischaemia which in turn is potentially responsible for severe morbidity (neurological deficit, neuropsychiatric disorders), poor quality of life (institutionalisation, inability to return to work) and increased mortality. Treatment with intravenous milrinone, an arterial vasodilator, has been proposed, but no randomised controlled study exists. We hypothesised that an intravenous infusion of milrinone would improve the neurological recovery of patients with vasospasm following aneurysmal SAH at 3 months.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>The MiVAR (Milrinone Infusion for VAsospam treatment in subarachnoid hemoRrhage) study is an investigator-initiated, phase III multicentre, randomised placebo-controlled, double-blinded, superiority trial evaluating the effect of intravenous milrinone versus placebo (saline), in patients with cerebral vasospasm following aneurysmal SAH. Patients will be included within 6\u2009hours of the confirmation of vasospasm diagnosis by a CT angiography and randomised to receive either milrinone (initial bolus of 0.1\u2009mg\/kg over 30\u2009min\u2014max 10 mg\u2014followed by a continuous infusion at 1\u2009\u00b5g\/kg\/min rate for at least 48 hours) or placebo. Milrinone (or placebo) could be increased to 1.5\u2009\u00b5g\/kg\/min. The dose is adapted according to the clinical and\/or transcranial Doppler response. 360 patients are expected to be included. The primary endpoint is the proportion of patients with a good neurological outcome at 3 months, defined as a modified Rankin score \u22642, obtained through a centralised standardised telephone interview (done by a unique trained team). The study started in August 2020, and the expected final follow-up is the last quarter of 2025. Analyses of the intention-to-treat and per-protocol populations are planned.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The MiVAR trial protocol has been approved by an ethics committee (Comit\u00e9 de Protection des Personnes Ouest V), by the Agence Nationale de S\u00e9curit\u00e9 du M\u00e9dicament (ANSM, Number 160\u2009828A-21, approval date 26 December 2019) and by the \u2018Commission Nationale Informatique et Libert\u00e9\u2019 (CNIL, decision DR-2020-076, approval date 21 February 2020). The study will be conducted according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. The MiVAR study will be the first multicentre randomised study to evaluate the efficacy of intravenous milrinone in improving the neurological outcomes at 3 months in patients with vasospasm following aneurysmal SAH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration numbers<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04362527\">NCT04362527<\/jats:ext-link>\n                      , EudractCT number 2019-002145-37.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-101483","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T18:25:33Z","timestamp":1761675933000},"page":"e101483","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Milrinone infusion for vasospasm treatment in subarachnoid haemorrhage: protocol for a double-blind randomised clinical trial \u2013 the MiVAR study"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct04362527","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct02714387","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04362527","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2901-4628","authenticated-orcid":false,"given":"Sigismond","family":"Lasocki","sequence":"first","affiliation":[{"name":"D\u00e9partement Anesth\u00e9sie R\u00e9animation, Angers University Hospital, Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5311-3987","authenticated-orcid":false,"given":"Karim","family":"Lakhal","sequence":"additional","affiliation":[{"name":"Anesth\u00e9sie et r\u00e9animation chirurgicale, H\u00f4pital Guillaume et Ren\u00e9 La\u00ebnnec, Centre Hospitalier Universitaire de Nantes, Nantes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugues","family":"de Courson","sequence":"additional","affiliation":[{"name":"CHU de Bordeaux, Talence, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Geslain","sequence":"additional","affiliation":[{"name":"CHU de Brest, Brest, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoann","family":"Launey","sequence":"additional","affiliation":[{"name":"H\u00f4pital Pontchaillou, Rennes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Pottecher","sequence":"additional","affiliation":[{"name":"Anesthesiology and Critical Care, Hopitaux universitaires de Strasbourg, Strasbourg, 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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Francois","family":"Hamel","sequence":"additional","affiliation":[{"name":"Methodology and Biostatistics Department, Angers University Hospital, Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maeva","family":"Campfort","sequence":"additional","affiliation":[{"name":"D\u00e9partement Anesth\u00e9sie R\u00e9animation, Angers University Hospital, Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Gaillard","sequence":"additional","affiliation":[{"name":"D\u00e9partement Anesth\u00e9sie R\u00e9animation, Angers University Hospital, Angers, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the MiVAR study group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the ATLANREA 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