Treatment of Vasospasm of Aneurysmal Subarachnoid Hemorrhage With Intrathecal Nicardipine - FAST-IT Trial

Официальное название

Trial of Treatment of Vasospasm Associated With Aneurysmal Subarachnoid Hemorrhage With Intrathecal Injection of Nicardipine: a Multi-center, Prospective, Double-blinded, Randomized Controlled Trial

Обзор

To investigate whether patients with cerebral vasospasm associated with aneurysmal subarachnoid hemorrhage have a better prognosis with intrathecal nicardipine injection via extraventricular drainage or lumbar drainage.

Подробное описание

Objective:

To investigate whether patients with cerebral vasospasm associated with aneurysmal subarachnoid hemorrhage have a better prognosis with intrathecal nicardipine injection via extraventricular drainage or lumbar drainage.

Design:

This study is a multi-center, prospective, double-blinded, randomized controlled trial.

Interventions:

First, 6 ml of cerebrospinal fluid is withdrawn from the EVD or LD catheter, and then 4 ml of nicardipine hydrochloride is injected into the EVD or LD drain tube, followed by 2 ml of 0.9 % sodium chloride solution (NaCl), and then the EVD or LD tube was clamped for 2 hours after the injection was completed, then kept open as clinically necessary until the next dose (twice a day).

Вмешательства

• Препарат Intrathecal Nicardipine
  First, 6 ml of cerebrospinal fluid is withdrawn from the EVD or LD catheter, and then 4 ml (4mg) of nicardipine is injected into the EVD or LD drain tube, followed by 2 ml normal saline solution, and then the EVD or LD tube is clamped for 2 hours, and then kept open as clinically necessary until the next dose (q12h) of medication.
• Другое No intervention
  A simulated "intrathecal administration" operation is performed by a dedicated physician who is unblinded to the group assignment, the EVD or LD tube is not opened, and no "drug" is given. The simulated administration process needs to be out of the patient's view (if awake patient) and out of the presence of study team personnel.

Первичные конечные точки

• Dichotomized Modified Rankin Scale (mRS) 0-2 vs 3-6 [Срок оценки: Day 90±30, Day 365±60.]

Вторичные конечные точки (11)

• Extended Glasgow Outcome Score (GOS-E). [Срок оценки: Day 90±30, Day 365±60.]
• Modified Rankin Scale ordinal shift with mRS 5 and 6 combined [Срок оценки: Day 90±30, Day 365±60.]
• Dichotomized Modified Rankin Scale (mRS) 0-3 vs 4-6 [Срок оценки: Day 90±30, Day 365±60.]
• Mini-Mental State Examination (MMSE) score [Срок оценки: Day 90±30, Day 365±60.]
• Change of National Institutes of Health Stroke Scale (NIHSS) score [Срок оценки: At discharge]
• Cerebrospinal fluid shunt surgery rate [Срок оценки: Day 90±30, Day 365±60.]
• Overall mortality rate [Срок оценки: Day 90±30, Day 365±60.]
• Rate of CSF infection [Срок оценки: Day 30±7]
• Rate of any type of new intracranial hemorrhage. [Срок оценки: Day 90±30, Day 365±60.]
• Adverse Event [Срок оценки: Baseline, Day 2-21, Day 90±30, Day 365±60.]
• Serious Adverse Event [Срок оценки: Baseline, Day 2-21, Day 90±30, Day 365±60.]

Критерии участия

Критерии включения

• Age 18-80.
• Spontaneous SAH confirmed by head CT.
• Saccular brain aneurysm is identified and treated, either surgically or endovascularly.
• SAH Fisher grade >1 or modified Fisher grade >0.
• EVD placed for acute hydrocephalus, or LD placed for draining bloody CSF as deemed necessary by the treating physician.
• Any clinical scenario leading to the diagnosis of possible vasospasm, which includes:

• Mean flow velocity of MCA >120, or Lindegaard Ratio ( LR ) > 3.
• Any intracranial artery including MCA, ACA, PCA, and BA, TCD showed an upward trend of mean flow velocity for 2 consecutive days (>25cm/s/day).
• Clinical deterioration including mental status change (GCS score decrease > 2) and focal neurological deficit unable to be attributed to other known neurological reasons.
• Evidence of vasospasm on CTA or DSA, or ischemic change by CTP, MRI.
• Within 14 days of onset of SAH.
• Informed consent obtained from the patient or family member.

Критерии исключения

• Hunt-Hess Grade 5 or WFNS Grade 5 (no clinical improvement after EVD placement for acute hydrocephalus).
• Bacterial or distal aneurysms without subarachnoid hemorrhage in the basal cisterns.
• The treating physician determines that the culprit aneurysm has not been fully repaired, with a very high likelihood of rebleeding in the near term.
• History of head trauma within the past 3 months.
• Any recent brain disease within 3 months, such as tumors, stroke, epilepsy, vasculitis, arteriovenous malformation, hydrocephalus, etc.
• History of psychiatric disorders or seizures within 3 months.
• Severe concurrent medical conditions.
• Pregnant women or those of childbearing potential with a positive urine or serum β-human chorionic gonadotropin (HCG) test.
• Lactating women.
• Life expectancy of less than 1 year prior to aSAH onset.
• Pre-morbid mRS score >1.
• Participation in another randomized clinical trial that may confound the evaluation of this study.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 28 центров

• Affiliated First Hospital of Anhui Medical University — Хэфэй
• Beijing Tiantan Hospital, Affiliated to Capital Medical University — Пекин
• Chongqing Ninth People's Hospital — Чунцин
• Southern Medical University Zhujiang Hospital — Гуанчжоу
• Affiliated South China Hospital of Shenzhen University — Шэньчжэнь
• Nanning First People's Hospital — Nanning
• Jinyang Hospital Affiliated to Guizhou Medical University — Guiyang
• The Second Affiliated Hospital of Guizhou Medical University — Kaili
• … и ещё 20 центров

Публикации

• Wartenberg KE, Schmidt JM, Claassen J, Temes RE, Frontera JA, Ostapkovich N, Parra A, Connolly ES, Mayer SA. Impact of medical complications on outcome after subarachnoid hemorrhage. Crit Care Med. 2006 Mar;34(3):617-23; quiz 624. doi: 10.1097/01.ccm.0000201903.46435.35. PMID 16521258
• Al-Khindi T, Macdonald RL, Schweizer TA. Cognitive and functional outcome after aneurysmal subarachnoid hemorrhage. Stroke. 2010 Aug;41(8):e519-36. doi: 10.1161/STROKEAHA.110.581975. Epub 2010 Jul 1. PMID 20595669
• Vergouwen MD; Participants in the International Multi-Disciplinary Consensus Conference on the Critical Care Management of Subarachnoid Hemorrhage. Vasospasm versus delayed cerebral ischemia as an outcome event in clinical trials and observational studies. Neurocrit Care. 2011 Sep;15(2):308-11. doi: 10.1007/s12028-011-9586-8. PMID 21748502
• Macdonald RL, Hunsche E, Schuler R, Wlodarczyk J, Mayer SA. Quality of life and healthcare resource use associated with angiographic vasospasm after aneurysmal subarachnoid hemorrhage. Stroke. 2012 Apr;43(4):1082-8. doi: 10.1161/STROKEAHA.111.634071. Epub 2012 Feb 9. PMID 22328549
• Springer MV, Schmidt JM, Wartenberg KE, Frontera JA, Badjatia N, Mayer SA. Predictors of global cognitive impairment 1 year after subarachnoid hemorrhage. Neurosurgery. 2009 Dec;65(6):1043-50; discussion 1050-1. doi: 10.1227/01.NEU.0000359317.15269.20. PMID 19934963
• Pegoli M, Mandrekar J, Rabinstein AA, Lanzino G. Predictors of excellent functional outcome in aneurysmal subarachnoid hemorrhage. J Neurosurg. 2015 Feb;122(2):414-8. doi: 10.3171/2014.10.JNS14290. Epub 2014 Dec 12. PMID 25495745
• Frontera JA, Fernandez A, Schmidt JM, Claassen J, Wartenberg KE, Badjatia N, Connolly ES, Mayer SA. Defining vasospasm after subarachnoid hemorrhage: what is the most clinically relevant definition? Stroke. 2009 Jun;40(6):1963-8. doi: 10.1161/STROKEAHA.108.544700. Epub 2009 Apr 9. PMID 19359629
• Vergouwen MD, Vermeulen M, van Gijn J, Rinkel GJ, Wijdicks EF, Muizelaar JP, Mendelow AD, Juvela S, Yonas H, Terbrugge KG, Macdonald RL, Diringer MN, Broderick JP, Dreier JP, Roos YB. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke. 2010 Oct;41(1 PMID 20798370

Идентификаторы

NCT: NCT06329635 · 2023070K

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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