Intra-Arterial Magnesium Therapy After Mechanical Thrombectomy in Acute Ischemic Stroke

Обзор

The goal of this Phase I unblinded, dose-escalation trial is to evaluate the safety and tolerability of intra-arterial magnesium sulfate injection after mechanical thrombectomy in patients experiencing acute ischemic stroke. This trial is one of the first trials to look at IA administration of magnesium sulfate into at risk brain tissue in a selective and localized fashion.

Подробное описание

Patients meeting inclusion and exclusion criteria will undergo a baseline neurologic assessment and will be enrolled following informed consent. The patient will then be taken to the Interventional Radiology suite where the patient will undergo MT as per the standard of care. Participation in this study will never delay the timely provision of urgent MT to patients.

Additionally, as part of the study procedure, the patient will be assigned to Treatment Group 1,2, 3 or 4 based on the consecutive sampling scheme. The first 6 patients enrolled will be in group 1 and receive the lowest dose of MgSO4 as described below. If the analysis of this group deems this dosage to be safe, the following patients will be enrolled into group 2. The same scheme will be followed until all 4 groups are enrolled.

Patients in all groups will receive IA MgSO4 as follows (investigational):

Patients in each group will receive the specified dose of MgSO4 (listed below) diluted in 0.9% sodium chloride. The infusion of IA MgSO4 will be administered over 1-2 minutes.

Dose Escalation Schedule Group 1 0.25g IA MgSO4 Group 2 0.5g IA MgSO4 Group 3 1g IA MgSO4 Group 4 1.5g IA MgSO4

Given the minimal safety data on IA MgSO4, this dosage regimen was derived from previous IV MgSO4 studies and a singular IA MgSO4 study in a separate population to cautiously investigate the safety and tolerability for IA MgSO4.

Following MT and IA infusion, patients will receive a continuous infusion of IV MgSO4 for 24 hours. The maintenance infusion will contain 16g of MgSO4 diluted in 240 ml of 0.9% normal saline, infused at a rate of 10 ml per hour for 24 hours. Patients will follow the standard of care monitoring for post-MT patients with the addition of monitoring for magnesium toxicity.

All pre and post imaging is standard of care for this procedure, including follow up MRI (or CT if MRI contraindicated).

Following discharge from the hospital, all patients enrolled in the study protocol will be followed up in the clinic at 3 months to evaluate the patient's functional clinical outcome. If for any reason, the patient cannot come back for a follow-up visit, the PI/Co-PI's will contact the patient via phone/email to gather the required data. A minimum of mRS and NIHSS should be gathered for follow-up data.

Вмешательства

• Препарат Magnesium sulfate
  Following MT and IA injection of MgSO4, patients will also receive a continuous infusion of 16g MgSO4 diluted in 240 ml of 0.9% normal saline, infusing at a rate of 10 ml per hour for 24 hours.

Первичные конечные точки

• Systemic MgSO4 Concentration [Срок оценки: 6 hours post-MT, 24 hours post-MT]
• Proportion of severe adverse events [Срок оценки: 48 hours post-MT]

Вторичные конечные точки (6)

• Proportion of patients with Modified Rankin Scale (mRS) 0 to 2 [Срок оценки: 90 days post-MT]
• Modified Rankin Scales (mRS) [Срок оценки: 90 days post-MT]
• Decrease in National Institutes of Health Stroke Scale (NIHSS) [Срок оценки: 48 hours post-MT]
• Proportion of symptomatic intracranial hemorrhage (sICH) [Срок оценки: 48 hours post-MT]
• Proportion of hemorrhagic transformation [Срок оценки: 48 hours post-MT]
• All causes of death after treatment [Срок оценки: 48 hours post-MT, 90 days post-MT]

Критерии участия

Критерии включения

• Patient with acute cerebral ischemia due to ICA or MCA occlusion
• Major neurologic deficits: 6≤NIHSS≤20,
• Premorbid mRS 0 or 1, or 2
• Patient's clinical attending physician plans MT procedure as part of routine clinical care,
• undergo MT with a TICI 2a or better recanalization,
• Signed informed consent.

Критерии исключения

• Positive pregnancy test;
• those undergoing MT with a TICI <2a revascularization;
• tandem occlusion of the cervical common or internal carotid artery; and
• subjects on therapeutic anticoagulation, as it is a relative contraindication to MT, and could be a confounding variable predisposing to intracranial hemorrhage including coagulation disorders, systematic hemorrhagic tendency, thrombocytopenia <80000/mm3;
• Second or third-degree heart block without a pacemaker in place,
• Technical inability to navigate micro-catheter to target clot,
• Patient already enrolled in another experimental treatment trial. Exclusion criteria 1-3 are all contraindications to magnesium therapy,
• mRS>2 caused by a history of prior stroke,
• Severe hepatic dysfunction, severe renal dysfunction (<30 mL/min), increase in ALT or AST (more than 2 times of upper limit of normal value), increase in serum creatinine (more than 1.5 times of upper limit of normal value) or requiring dialysis;
• Unsuitable for this clinical study assessed by researcher. Subjects will not be excluded if they received IV t-PA as standard of care.
• patient is on neuromuscular blocking agents including depolarizing (succinylcholine) and nondepolarizing subtypes (rocuronium, vecuronium, etc);
• patient is taking any form of CNS depressant including barbiturates, narcotics, outside the setting of anesthesia or ICU sedation
• patients taking digoxin or other cardiac glycoside

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Badhiwala JH, Nassiri F, Alhazzani W, Selim MH, Farrokhyar F, Spears J, Kulkarni AV, Singh S, Alqahtani A, Rochwerg B, Alshahrani M, Murty NK, Alhazzani A, Yarascavitch B, Reddy K, Zaidat OO, Almenawer SA. Endovascular Thrombectomy for Acute Ischemic Stroke: A Meta-analysis. JAMA. 2015 Nov 3;314(17):1832-43. doi: 10.1001/jama.2015.13767. PMID 26529161
• Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Davalos A, Majoie CB, van der Lugt A, de Miquel MA, Donnan GA, Roos YB, Bonafe A, Jahan R, Diener HC, van den Berg LA, Levy EI, Berkhemer OA, Pereira VM, Rempel J, Millan M, Davis SM, Roy D, Thornton J, Roman LS, Ribo M, Beumer D, Stouch B, Brown S, Campbell BC, van Oostenbrugge RJ, Saver JL, Hill MD, Jovin TG; HERMES collaborator PMID 26898852
• Kral T, Luhmann HJ, Mittmann T, Heinemann U. Role of NMDA receptors and voltage-activated calcium channels in an in vitro model of cerebral ischemia. Brain Res. 1993 May 28;612(1-2):278-88. doi: 10.1016/0006-8993(93)91673-g. PMID 8101132
• Bennion DM, Jones CH, Dang AN, Isenberg J, Graham JT, Lindblad L, Domenig O, Waters MF, Poglitsch M, Sumners C, Steckelings UM. Protective effects of the angiotensin II AT2 receptor agonist compound 21 in ischemic stroke: a nose-to-brain delivery approach. Clin Sci (Lond). 2018 Mar 15;132(5):581-593. doi: 10.1042/CS20180100. Print 2018 Mar 15. PMID 29500223
• Saver JL, Starkman S, Eckstein M, Stratton SJ, Pratt FD, Hamilton S, Conwit R, Liebeskind DS, Sung G, Kramer I, Moreau G, Goldweber R, Sanossian N; FAST-MAG Investigators and Coordinators. Prehospital use of magnesium sulfate as neuroprotection in acute stroke. N Engl J Med. 2015 Feb 5;372(6):528-36. doi: 10.1056/NEJMoa1408827. PMID 25651247
• Muir KW, Lees KR, Ford I, Davis S; Intravenous Magnesium Efficacy in Stroke (IMAGES) Study Investigators. Magnesium for acute stroke (Intravenous Magnesium Efficacy in Stroke trial): randomised controlled trial. Lancet. 2004 Feb 7;363(9407):439-45. doi: 10.1016/S0140-6736(04)15490-1. PMID 14962524
• Griauzde J, Ravindra VM, Chaudhary N, Gemmete JJ, Pandey AS. Neuroprotection for ischemic stroke in the endovascular era: A brief report on the future of intra-arterial therapy. J Clin Neurosci. 2019 Nov;69:289-291. doi: 10.1016/j.jocn.2019.08.001. Epub 2019 Aug 17. PMID 31431407
• Muir KW. Magnesium for neuroprotection in ischaemic stroke: rationale for use and evidence of effectiveness. CNS Drugs. 2001;15(12):921-30. doi: 10.2165/00023210-200115120-00002. PMID 11735612

Идентификаторы

NCT: NCT06956521 · H-50731

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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