Prehospital transdermal glyceryl trinitrate in patients with presumed acute stroke (MR ASAP)
| العنوان: | Prehospital transdermal glyceryl trinitrate in patients with presumed acute stroke (MR ASAP) |
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| المؤلفون: | Sophie A van den Berg, Simone M Uniken Venema, Hendrik Reinink, Jeannette Hofmeijer, Wouter J Schonewille, Irene Miedema, Puck S S Fransen, D Martijn O Pruissen, Theodora W M Raaijmakers, Gert W van Dijk, Frank-Erik de Leeuw, Jorine A van Vliet, Vincent I H Kwa, Henk Kerkhoff, Alex van 't Net, Rene Boomars, Arjen Siegers, Tycho Lok, Klaartje Caminada, Laura M Esteve Cuevas, Marieke C Visser, Casper P Zwetsloot, Jooske M F Boomsma, Mirjam H Schipper, Roeland P J van Eijkelenburg, Olvert A Berkhemer, Daan Nieboer, Hester F Lingsma, Bart J Emmer, Robert J van Oostenbrugge, Aad van der Lugt, Yvo B W E M Roos, Charles B L M Majoie, Diederik W J Dippel, Paul J Nederkoorn, H Bart van der Worp, Ayla van Ahee, Frank Visseren, Patricia Halkes, Ruben van Eijk, Michelle Simons, Wilma Pellikaan, Wilma Van Wijngaarden, Eva Ponjee, Petra Geijtenbeek, Ton Arts, Elles Zock, Wilma Oudshoorn, Frans Steenwinkel, Hamdia Samim, Mark van Zandwijk, Lisette Vrielink, Peter Jan Mulder, Aico Gerritsen, Jim Ijzermans, Marjan Kooijman, Oscar Francissen, Rick van Nuland, Wim van Zwam, Linda Jacobi, Rene van den Berg, Ludo Beenen, Adriaan van Es, Pieter-Jan van Doormaal, Geert Lycklama a Nijeholt, Ido van den Wijngaard, Albert Yoo, Lonneke Yo, Jasper Martens, Bas Hammer, Stefan Roosendaal, Anton Meijer, Menno Krietemeijer, Reinoud Bokkers, Anouk van der Hoorn, Dick Gerrits, Jonathan Coutinho, Ben Jansen, Sanne Manschot, Peter Koudstaal, Koos Keizer, Vicky Chalos, Adriaan Versteeg, Lennard Wolff, Henk van Voorst, Matthijs van der Sluijs, Arnolt-Jan Hoving, Kilian Treurniet, Natalie LeCouffe, Rob van de Graaf, Robert-Jan Goldhoorn, Wouter Hinseveld, Anne Pirson, Lotte Sondag, Manon Kappelhof, Manon Tolhuisen, Josje Brouwer, Wouter van der Steen, Leon Rinkel, Agnetha Bruggeman, Rita Sprengers, Martin Sterrenberg, Sabrina Verheesen, Leontien Heiligers, Yvonne Martens, Naziha El Ghannouti, Miranda Slotboom |
| المساهمون: | MUMC+: MA Neurologie (3), MUMC+: Hersen en Zenuw Centrum (3), Klinische Neurowetenschappen, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, RS: Carim - B05 Cerebral small vessel disease, Graduate School, ACS - Atherosclerosis & ischemic syndromes, ANS - Neurovascular Disorders, Neurology, Radiology and Nuclear Medicine, ANS - Cellular & Molecular Mechanisms, ACS - Microcirculation, ACS - Pulmonary hypertension & thrombosis, Biomedical Engineering and Physics, ANS - Brain Imaging, ANS - Compulsivity, Impulsivity & Attention, Radiology & Nuclear Medicine, Public Health, Radiology and nuclear medicine, Pediatrics, Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), TechMed Centre, Clinical Neurophysiology |
| المصدر: | Lancet Neurology, 21(11), 971-981. Elsevier Science MR ASAP Investigators 2022, ' Prehospital transdermal glyceryl trinitrate in patients with presumed acute stroke (MR ASAP) : an ambulance-based, multicentre, randomised, open-label, blinded endpoint, phase 3 trial ', The Lancet Neurology, vol. 21, no. 11, pp. 971-981 . https://doi.org/10.1016/S1474-4422Test(22)00333-7 The Lancet Neurology, 21(11), 971-981. Lancet Publishing Group Lancet Neurology, 21, 971-981 Lancet Neurology, 21, 11, pp. 971-981 Lancet Neurology, 21(11), 971-981. ELSEVIER SCIENCE INC |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Adult, Adolescent, Ischemic Attack, Transient, Nitroglycerin/therapeutic use, Ambulances, Brain Ischemia/drug therapy, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Brain Ischemia, Stroke, Nitroglycerin, Treatment Outcome, Ischemic Attack, Transient, 2023 OA procedure, Humans, Neurology (clinical), Stroke/drug therapy, Cerebral Hemorrhage/drug therapy, Cerebral Hemorrhage, Ischemic Stroke |
| الوصف: | Contains fulltext : 287508.pdf (Publisher’s version ) (Closed access) BACKGROUND: Pooled analyses of previous randomised studies have suggested that very early treatment with glyceryl trinitrate (also known as nitroglycerin) improves functional outcome in patients with acute ischaemic stroke or intracerebral haemorrhage, but this finding was not confirmed in a more recent trial (RIGHT-2). We aimed to assess whether patients with presumed acute stroke benefit from glyceryl tr initrate started within 3 h after symptom onset. METHODS: MR ASAP was a phase 3, randomised, open-label, blinded endpoint trial done at six ambulance services serving 18 hospitals in the Netherlands. Eligible participants (aged ≥18 years) had a probable diagnosis of acute stroke (as assessed by a paramedic), a face-arm-speech-time test score of 2 or 3, systolic blood pressure of at least 140 mm Hg, and could start treatment within 3 h of symptom onset. Participants were randomly assigned (1:1) by ambulance personnel, using a secure web-based electronic application with random block sizes stratified by ambulance service, to receive either transdermal glyceryl trinitrate 5 mg/day for 24 h plus standard care (glyceryl trinitrate group) or to standard care alone (control group) in the prehospital setting. Informed consent was deferred until after arrival at the hospital. The primary outcome was functional outcome assessed with the modified Rankin Scale (mRS) at 90 days. Safety outcomes included death within 7 days, death within 90 days, and serious adverse events. Analyses were based on modified intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. We separately analysed the total population and the target population (ie, patients with intracerebral haemorrhage, ischaemic stroke, or transient ischaemic attack). The target sample size was 1400 patients. The trial is registered as ISRCTN99503308. FINDINGS: On June 24, 2021, the MR ASAP trial was prematurely terminated on the advice of the data and safety monitoring board, with recruitment stopped because of safety concerns in patients with intracerebral haemorrhage. Between April 4, 2018, and Feb 12, 2021, 380 patients were randomly allocated to a study group. 325 provided informed consent or died before consent could be obtained, of whom 170 were assigned to the glyceryl trinitrate group and 155 to the control group. These patients were included in the total population. 201 patients (62%) had ischaemic stroke, 34 (10%) transient ischaemic attack, 56 (17%) intracerebral haemorrhage, and 34 (10%) a stroke-mimicking condition. In the total population (n=325), the median mRS score at 90 days was 2 (IQR 1-4) in both the glyceryl trinitrate and control groups (adjusted common OR 0·97 [95% CI 0·65-1·47]). In the target population (n=291), the 90-day mRS score was 2 (2-4) in the glyceryl trinitrate group and 3 (1-4) in the control group (0·92 [0·59-1·43]). In the total population, there were no differences between the two study groups with respect to death within 90 days (adjusted OR 1·07 [0·53-2·14]) or serious adverse events (unadjusted OR 1·23 [0·76-1·99]). In patients with intracerebral haemorrhage, 12 (34%) of 35 patients allocated to glyceryl trinitrate versus two (10%) of 21 allocated to the control group died within 7 days (adjusted OR 5·91 [0·78-44·81]); death within 90 days occurred in 16 (46%) of 35 in the glyceryl trinitrate group and 11 (55%) of 20 in the control group (adjusted OR 0·87 [0·18-4·17]). INTERPRETATION: We found no sign of benefit of transdermal glyceryl trinitrate started within 3 h of symptom onset in the prehospital setting in patients with presumed acute stroke. The signal of potential early harm of glyceryl trinitrate in patients with intracerebral haemorrhage suggests that glyceryl trinitrate should be avoided in this setting. FUNDING: The Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1474-4422 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7ee59631545f126c08786122d88c5021Test https://hdl.handle.net/11370/4be8e5ea-ce73-44cc-9467-53e548a0319eTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....7ee59631545f126c08786122d88c5021 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14744422 |
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