Cilostazol for Preventing Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage

Официальное название

Cilostazol for Preventing Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage: A Prospective, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Trial

Обзор

The investigators propose to conduct a multicenter randomized trial to test whether cilostazol reduces the incidence of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) and improves patients' neurological prognosis, while assessing its safety.

Подробное описание

The investigators propose to conduct a multicenter randomized trial to test the primary hypothesis of whether cilostazol reduces the incidence of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) and improves patients' neurological prognosis, while assessing its safety. The investigators will recruit 316 patients from 30 hospitals in China. Eligibility criteria for the trial participants include Aged 18-80 years. Diagnosed with subarachnoid hemorrhage (SAH) by computed tomography (CT) scan, and the responsible aneurysm is identified by computed tomography angiography (CTA) or digital subtraction angiography (DSA). Received aneurysm coil embolization or craniotomy clipping within 72 hours of symptom onset. Hunt-Hess grade II-IV. No rebleeding or new intracranial hemorrhage is shown on head CT within 6 hours after surgery. Understand and follow the procedures of clinical trial, participate voluntarily and sign the informed consent (the informed consent can be signed voluntarily by the person or guardian). Patients with multiple aneurysms, Modified Rankin Scale (mRS) score ≥ 3 before onset, contraindications to cilostazol use, severe organic diseases and an expected survival time of less than 90 days, severe liver insufficiency or renal insufficiency before randomization, aneurysm treatment requiring the use of other antiplatelet drugs after interventional therapy, receiving treatment with other investigational drugs or device trials currently will be excluded. Patients will be randomly assigned to the experimental group or control group at a 1:1 ratio. Experimental Group patients will receive cilostazol 100 mg twice daily for 14 consecutive days, in addition to the standard aSAH treatment. Control Group patients will receive a placebo twice daily (bid) for 14 consecutive days, in addition to the standard aSAH treatment. The primary study endpoint is incidence of delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH) within 14±2 days after randomization. Other secondary endpoints include neurological function prognosis at 90±7 days after randomization, incidence of intracranial rebleeding events within 90±7 days after randomization, incidence of other severe bleeding events within 90±7 days after randomization. This trial will provide important information for the development of clinical guidelines for reducing delayed cerebral ischemia (DCI) in patients with aneurysmal subarachnoid hemorrhage (aSAH).

Вмешательства

• Препарат Cilostazol 100 mg BID
  Within 24 hours after randomization, patients will receive cilostazol 100 mg twice daily (BID) for 14 consecutive days, in addition to the standard aSAH treatment.
• Препарат placebo
  Within 24 hours after randomization, patients will receive a placebo twice daily (BID) for 14 consecutive days, in addition to the standard aSAH treatment.

Первичные конечные точки

• Incidence of delayed cerebral ischemia (DCI) [Срок оценки: At 14±2 days after randomization]

Вторичные конечные точки (3)

• Neurological function prognosis [Срок оценки: At 90 days after randomization]
• Incidence of intracranial rebleeding events [Срок оценки: At 90±7 days after randomization]
• Incidence of other severe bleeding events [Срок оценки: At 90 days after randomization]

Критерии участия

Критерии включения

• Aged 18-80 years.
• Diagnosed with subarachnoid hemorrhage (SAH) by computed tomography (CT) scan, and the responsible aneurysm is clearly identified by computed tomography angiography (CTA) or digital subtraction angiography (DSA).
• Received aneurysm coil embolization or craniotomy clipping within 72 hours of symptom onset.
• Hunt-Hess grade II-IV.
• No rebleeding or new intracranial hemorrhage is shown on head CT within 6 hours after surgery.
• Understand and follow the procedures of clinical trial, participate voluntarily and sign the informed consent (the informed consent can be signed voluntarily by the person or guardian)

Критерии исключения

• Multiple aneurysms (>1aneurysms confirmed by CTA/DSA)
• Modified Rankin Scale (mRS) score ≥ 3 before onset
• Patients with contraindications to cilostazol use:

• Allergy to cilostazol
• Severe heart failure（New York Heart Association (NYHA) Functional Classification Grade III or IV）
• Coagulation disorders or systemic bleeding (e.g., hemophilia, gastrointestinal bleeding, hemoptysis, etc.)
• Pregnant or lactating women
• Patients with severe organic diseases and an expected survival time of less than 90 days
• Severe liver insufficiency or renal insufficiency before randomization
• Aneurysm treatment requiring the use of other antiplatelet drugs after interventional therapy
• Currently receiving treatment with other investigational drugs or device trials

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 · 1 центр

• Beijing Tiantan Hospital, Capital Medical University — Пекин

Публикации

• SVIN COVID-19 Global SAH Registry. Global impact of the COVID-19 pandemic on subarachnoid haemorrhage hospitalisations, aneurysm treatment and in-hospital mortality: 1-year follow-up. J Neurol Neurosurg Psychiatry. 2022 Jul 28:jnnp-2022-329200. doi: 10.1136/jnnp-2022-329200. Online ahead of print. PMID 35902229
• Kim BJ, Lee EJ, Kwon SU, Park JH, Kim YJ, Hong KS, Wong LKS, Yu S, Hwang YH, Lee JS, Lee J, Rha JH, Heo SH, Ahn SH, Seo WK, Park JM, Lee JH, Kwon JH, Sohn SI, Jung JM, Navarro JC, Kang DW; PICASSO investigators. Prevention of cardiovascular events in Asian patients with ischaemic stroke at high risk of cerebral haemorrhage (PICASSO): a multicentre, randomised controlled trial. Lancet Neurol. 2018 PMID 29778364
• Suzuki S, Sayama T, Nakamura T, Nishimura H, Ohta M, Inoue T, Mannoji H, Takeshita I. Cilostazol improves outcome after subarachnoid hemorrhage: a preliminary report. Cerebrovasc Dis. 2011;32(1):89-93. doi: 10.1159/000327040. Epub 2011 Jun 11. PMID 21677432
• Matsuda N, Naraoka M, Ohkuma H, Shimamura N, Ito K, Asano K, Hasegawa S, Takemura A. Effect of Cilostazol on Cerebral Vasospasm and Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage: A Randomized, Double-Blind, Placebo-Controlled Trial. Cerebrovasc Dis. 2016;42(1-2):97-105. doi: 10.1159/000445509. Epub 2016 Apr 13. PMID 27070952
• Nakatsuka Y, Kawakita F, Yasuda R, Umeda Y, Toma N, Sakaida H, Suzuki H; , on behalf of the Prospective Registry for Searching Mediators of Neurovascular Events After Aneurysmal Subarachnoid Hemorrhage (pSEED) Group. Preventive effects of cilostazol against the development of shunt-dependent hydrocephalus after subarachnoid hemorrhage. J Neurosurg. 2017 Aug;127(2):319-326. doi: 10.3171/2016.5.JNS1 PMID 27494819
• Sugimoto K, Nomura S, Shirao S, Inoue T, Ishihara H, Kawano R, Kawano A, Oka F, Suehiro E, Sadahiro H, Shinoyama M, Oku T, Maruta Y, Hirayama Y, Hiyoshi K, Kiyohira M, Yoneda H, Okazaki K, Dreier JP, Suzuki M. Cilostazol decreases duration of spreading depolarization and spreading ischemia after aneurysmal subarachnoid hemorrhage. Ann Neurol. 2018 Dec;84(6):873-885. doi: 10.1002/ana.25361. Epub 20 PMID 30341966
• Qureshi AI, Akhtar IN, Ma X, Lodhi A, Bhatti I, Beall J, Broderick JP, Cassarly CN, Martin RH, Sharma R, Thakkar M, Suarez JI. Effect of Cilostazol in Animal Models of Cerebral Ischemia and Subarachnoid Hemorrhage: A Systematic Review and Meta-Analysis. Neurocrit Care. 2023 Jun;38(3):698-713. doi: 10.1007/s12028-022-01637-6. Epub 2022 Nov 30. PMID 36450971
• Yamaguchi-Okada M, Nishizawa S, Mizutani A, Namba H. Multifaceted effects of selective inhibitor of phosphodiesterase III, cilostazol, for cerebral vasospasm after subarachnoid hemorrhage in a dog model. Cerebrovasc Dis. 2009;28(2):135-42. doi: 10.1159/000223439. Epub 2009 Jun 5. PMID 19506373

Идентификаторы

NCT: NCT07249853 · CAPTAIN

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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