TicAgreLor versus placebo to prevent cerebral ISCHemia in anEuRysmal low grade SAH A double blinded randomised controlled study TALISCHER - SAH
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 274
- 试验地点
- 7
- 主要终点
- -Symptomatic and asymptomatic peri-procedural thromboembolic events (0-24hrs): • Angiographic : any event with clotting near the neck of the aneurysm or in distal branches and parent vessel occlusion in any vascular territory during procedure, and/or • Clinical : worsening neurological deficit ≥2pts on NIHSS from baseline and/or • Imaging : acute infarcts on 24h MRI. Acute qualifying infarcts for evaluation criteria will be defined as ≥ 5 hyperintense DWI lesions or a lesion larger than 10 mm
研究概览
简要总结
To evaluate in patients with a low grade aSAH (WFNS 1 to 3) occurred for less than 72 hours, the effect of 14 days course of ticagrelor (bolus of 180 mg then 90 mg twice daily) vs placebo, initiated at the beginning of the endovascular treatment of the aneurysm, on the ischemic complications. The ischemic complications are defined as peri-procedural symptomatic and asymptomatic thromboembolic events and/or neurological worsening due to delayed cerebral ischemia occurring within 14 days of the endovascular treatment of the aneurysm.
研究设计
- 分配方式
- Randomized
- 主要目的
- Ticagrelor
- 盲法
- Double (Carer, Subject, Monitor, Investigator, Analyst)
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Age 18 – 80 years old
- •Low grade aneurysmal subarachnoid hemorrhage defined by a WFNS 1-3
- •Aneurysmal treatment planned to be completed within 72 h after rupture
- •Sacciform aneurysm diameter ≥ 4 mm
- •Ruptured aneurysm treatable by endovascular, endo-saccular technic (stent and flow diverters are not allowed). If the aneurysm responsible of the SAH is difficult to identify, several aneurysms thaht may be related to the SAh can be treated during the procedure.
- •Affiliated person or beneficiary of a social security scheme
- •Free, informed and written consent signed by the participant or truthworthy/proxy representative and the investigator (at the latest on the day of inclusion and before any examination required by the research).
排除标准
- •Poor grade aSAH defined as WFNS 4 and 5
- •Intraparenchymal hematoma associated with SAH
- •Ongoing antiplatelet drug
- •Acute symptomatic hydrocephalus or ventricular derivation
- •Intra-ventricular hemorrhage on admission CT scan, filling >50% of both lateral ventricles and 3rd and 4th ventricles
- •Pre aSAH mRS ≥ 3
- •Active pathological bleeding and notably recent extra cranial hemorrhage (within previous 30 days), gastrointestinal hemorrhage within the past 6 months, or major surgery within 30 days
- •History of intracranial hemorrhage within the past 6 months
- •Other contra-indications to Ticagrelor: hypersensitivity to the active substance or to any of the excipients,
- •Severe hepatic or kidney failure,
- •Concomitant administration of strong CYP3A4 inhibitors (for ex ketoconazole, clarithromycine, nefazodone, ritonavir and atazanavir) and - drugs that interfered with P-glycoprotein transporter
- •Respiratory failure, asthma , obstructive broncho-pneumopathy
- •Pregnant and breastfeeding women
- •Patients under guardianship or other legal protection, deprived of their liberty by judicial or administrative decision
- •Fusiform, dissecting, thrombosed aneurysms and aneurysm associated with brain arteriovenous malformation
- •Associated unruptured aneurysm requiring treatment within 3 months
研究组 & 干预措施
Placebo du brilique
干预措施: Placebo du brilique (Drug)
Brilique 90 mg film-coated tablets
干预措施: Brilique 90 mg film-coated tablets (Drug)
结局指标
主要结局
-Symptomatic and asymptomatic peri-procedural thromboembolic events (0-24hrs): • Angiographic : any event with clotting near the neck of the aneurysm or in distal branches and parent vessel occlusion in any vascular territory during procedure, and/or • Clinical : worsening neurological deficit ≥2pts on NIHSS from baseline and/or • Imaging : acute infarcts on 24h MRI. Acute qualifying infarcts for evaluation criteria will be defined as ≥ 5 hyperintense DWI lesions or a lesion larger than 10 mm
-Symptomatic and asymptomatic peri-procedural thromboembolic events (0-24hrs): • Angiographic : any event with clotting near the neck of the aneurysm or in distal branches and parent vessel occlusion in any vascular territory during procedure, and/or • Clinical : worsening neurological deficit ≥2pts on NIHSS from baseline and/or • Imaging : acute infarcts on 24h MRI. Acute qualifying infarcts for evaluation criteria will be defined as ≥ 5 hyperintense DWI lesions or a lesion larger than 10 mm
次要结局
- Related to peri procedural asymptomatic and symptomatic TEE within 24 h of aneurysmal treatment : Occurrence of at least: • One peri procedural angiographic TEE • One peri procedural clinical TEE • A severe symptomatic ischemic lesion defined by worsening >4 pts on NIHSS from baseline • One peri procedural imaging TEE • One periprocedural TEE (angiographic and/or clinical and/or imaging)
- Related to neurological deterioration and asymptomatic lesions on MRI due to DCI Occurrence of at least • A neurological deterioration due to DCI • A severe neurologic deterioration due to DCI • Asymptomatic MRI lesions • One ischemic event (clinical/ MRI) related to DCI
- Combined incidence of all ischemic events: sum of both type of ischemic events (related to TEE and/or DCI) /patient at day 15
- Rate of rescue therapy during angiography and/ or DCI
- Aneurysm occlusion at procedure completion, 24 h, and 3months MRI-MRA (Raymond Roy classification)
- Clinical outcome at 3 months: • Rate of good Functional outcome: mRS<3 and GOSE> 5 • Quality of life assessed by EQ- 5D • Rate of cognitive deterioration defined by MoCA score ≤ 25 • Rate of deaths
- Occurrence of adverse events: • Aneurysmal rupture • Intracranial bleedings • Other major bleedings : Fatal bleeding, and/or symptomatic bleeding in a critical area or organ … • Minor bleedings • Non hemorrhagic adverse events of ticagrelor in particular rate of patients with dyspnea, bradyarythmia, increase uric acid and creatinemia measured at baseline (randomization) at day 7 and 15.
研究者
Lionel Calviére
Scientific
Centre Hospitalier Universitaire De Toulouse