TicAgreLor Versus Placebo to Prevent Cerebral ISCHemia in anEuRysmal Low Grade SAH A Double Blinded Randomised Controlled Study

After aSAH, ischemic complications such as peri‐procedural TEE and DCI prevalence are ashigh as 15 and 30% of the patients respectively. They are the main causes of disabilityin patients who survive the initial bleeding. The diagnoses of TEE and DCI may bedifficult in patients experiencing high grade aSAH contrariwise to low grade whereclinical exam and reliable imaging of brain ischemia could be performed. In addition,TEE/DCI dramatically impact the prognosis of these patients who had no/minor initialdeficit. Platelet activation and thrombo‐inflammatory mechanisms play a critical role inthe pathophysiology of TEE and DCI through multiple pathways. Several APD have beenevaluated to mitigate TEE/DCI risk with heterogeneous results. A recent metanalysissuggested that APD could reduce TEE incidence by 13 %. Interestingly patients receivingmono or dual APD just before aneurysmal repair did not experience an increasedhemorrhagic risk. Regarding DCI, aspirin failed to demonstrate any benefit in an Europeanrandomized controlled trial while 3 recent meta‐analyses suggested that APD use may beassociated with a relative risk reduction of 40‐50%. Hence, in the absence of positivetrials no APD use is not recommended for the management of aSAH. Compared to previous APDused in aSAH, Ticagrelor, a reversible P2Y12 receptor inhibitor, has a promising profileto control TEE/ DCI: stronger and shorter antiplatelet action as well as vasodilatory andanti‐inflammatory effects.Two hundred and seventy‐four patients will be randomized 1:1 in Ticagrelor or placebogroup within 72hrs of aneurysm rupture in a multicentre prospective double‐blind,parallel group study. Ticagrelor/placebo will be administered orally just before theendovascular treatment of the aneurysm with a loading dose of 180 mg, followed by 90 mgtwice a day during 2 weeks. We will assess a composite primary end point based on theoccurrence of ischemic complications: peri‐procedural asymptomatic and symptomatic TEEand/or neurological deterioration due to DCI. During the first 24H, TEE is defined byclotting or arterial occlusion on angiography during endovascular procedure and/or24hrs‐MRI infarctions and/or neurological deterioration defined by the worsening ≥2ptsfrom baseline on NIHSS performed immediately after the intervention, then every 6 hours.From day 2 to 15, multi daily clinical monitoring using NIHSS will be performed to assessthe occurrence of neurological deterioration due to DCI, defined as worsening ≥2pts onNIHSS, lasting for at least 2hrs. A brain imaging‐ MRI recommended‐ is needed in the caseof neurological deterioration to confirm its ischemic mechanism. Rescue therapies for DCIwill be feasible according to a decisional algorithm. Systematic MRI will be performedwithin the 24hrs of the endovascular procedure and 15 days after randomization in orderto detect, confirm and quantify cerebral infarcts. At 3 months, visit will includefunctional outcome with the mRS and the GOSE, cognitive functions with the MontrealCognitive Assessment (MoCA) and quality of life using EQ‐5D. Any hemorrhagic complicationrelated to SAH (rebleeding during the procedure, hydrocephalus requiring ventriculardrain, intracerebral hemorrhage) other major bleedings and side effects of the treatmentsuch as dyspnea will be carefully monitored and reported.