TicAgreLor Versus Placebo to Prevent Cerebral ISCHemia in anEuRysmal Low Grade SAH A Double Blinded Randomised Controlled Study (TALISCHER-SAH)
調査の概要
状態
条件
詳細な説明
After aSAH, ischemic complications such as peri-procedural TEE and DCI prevalence are as high as 15 and 30% of the patients respectively. They are the main causes of disability in patients who survive the initial bleeding. The diagnoses of TEE and DCI may be difficult in patients experiencing high grade aSAH contrariwise to low grade where clinical 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 initial deficit. Platelet activation and thrombo-inflammatory mechanisms play a critical role in the pathophysiology of TEE and DCI through multiple pathways. Several APD have been evaluated to mitigate TEE/DCI risk with heterogeneous results. A recent metanalysis suggested that APD could reduce TEE incidence by 13 %. Interestingly patients receiving mono or dual APD just before aneurysmal repair did not experience an increased hemorrhagic risk. Regarding DCI, aspirin failed to demonstrate any benefit in an European randomized controlled trial while 3 recent meta-analyses suggested that APD use may be associated with a relative risk reduction of 40-50%. Hence, in the absence of positive trials no APD use is not recommended for the management of aSAH. Compared to previous APD used in aSAH, Ticagrelor, a reversible P2Y12 receptor inhibitor, has a promising profile to control TEE/ DCI: stronger and shorter antiplatelet action as well as vasodilatory and anti-inflammatory effects.
Two hundred and seventy-four patients will be randomized 1:1 in Ticagrelor or placebo group within 72hrs of aneurysm rupture in a multicentre prospective double-blind, parallel group study. Ticagrelor/placebo will be administered orally just before the endovascular treatment of the aneurysm with a loading dose of 180 mg, followed by 90 mg twice a day during 2 weeks. We will assess a composite primary end point based on the occurrence of ischemic complications: peri-procedural asymptomatic and symptomatic TEE and/or neurological deterioration due to DCI. During the first 24H, TEE is defined by clotting or arterial occlusion on angiography during endovascular procedure and/or 24hrs-MRI infarctions and/or neurological deterioration defined by the worsening ≥2pts from 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 assess the occurrence of neurological deterioration due to DCI, defined as worsening ≥2pts on NIHSS, lasting for at least 2hrs. A brain imaging- MRI recommended- is needed in the case of neurological deterioration to confirm its ischemic mechanism. Rescue therapies for DCI will be feasible according to a decisional algorithm. Systematic MRI will be performed within the 24hrs of the endovascular procedure and 15 days after randomization in order to detect, confirm and quantify cerebral infarcts. At 3 months, visit will include functional outcome with the mRS and the GOSE, cognitive functions with the Montreal Cognitive Assessment (MoCA) and quality of life using EQ-5D. Any hemorrhagic complication related to SAH (rebleeding during the procedure, hydrocephalus requiring ventricular drain, intracerebral hemorrhage) other major bleedings and side effects of the treatment such as dyspnea will be carefully monitored and reported.
研究の種類
入学 (推定)
段階
- フェーズ 3
連絡先と場所
研究連絡先
- 名前：Lionel Calvière, MD
- 電話番号：+33 05 61 77 94 86
- メール：calviere.l@chu-toulouse.fr
研究場所
-
-
-
Bordeaux、フランス、33 000
- GH Pellegrin
-
主任研究者：
- Gaultier Marnat, MD
-
コンタクト：
- Gaultier Marnat, MD
- 電話番号：+33 05 57 82 17 65
- メール：gaultier.marnat@chu-bordeaux.fr
-
Montpellier、フランス、34 295
- Gui de Chauliac Hospital - Montpellier University Hospital
-
コンタクト：
- Kevin Chalard, MD
- 電話番号：+33 04 67 33 76 87
- メール：k-chalard@chu-montpellier.fr
-
主任研究者：
- Kevin Chalard, MD
-
Nantes、フランス、44 800
- Nord Laennec Hospital - Nantes University Hospital
-
コンタクト：
- Jean-Marc Le Goff, MD
- 電話番号：+33 02 40 16 53 04
- メール：jeanmarc.legoff@chu-nantes.fr
-
主任研究者：
- Jean-Marc Le Goff, MD
-
Paris、フランス、75 019
- Fondation Adolphe de Rothschild Hospital
-
コンタクト：
- Arthur Gutter, MD
- 電話番号：+33 01 48 03 68 31
- メール：agutter@for.paris
-
主任研究者：
- Arthur Gutter, MD
-
Strasbourg、フランス、67 200
- Hautepierre Hospital - Strasbourg Hospital University
-
コンタクト：
- Raoul Pop, MD
- 電話番号：+33 03 88 12 78 71
- メール：raoul.pop@chru-strasbourg.fr
-
主任研究者：
- Raoul Pop, MD
-
Toulouse、フランス、31 300
- Pierre Paul Riquet Hospital - Toulouse University Hospital
-
コンタクト：
- Lionel Calvière, MD
- 電話番号：+33 05 61 77 94 86
- メール：calviere.l@chu-toulouse.fr
-
主任研究者：
- Lionel Calvière, MD
-
Tours、フランス、37 000
- Bretonneau Hospital - Tours Regional University Hospital
-
コンタクト：
- Heloise Ifergan, MD
- 電話番号：+33 06 61 61 67 51
- メール：h.ifergan@chu-tours.fr
-
主任研究者：
- Heloise Ifergan, MD
-
-
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- 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 that 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).
Exclusion Criteria:
- Poor grade aSAH defined as WFNS 4 and 5
- Fusiform, dissecting, thrombosed aneurysms and aneurysm associated with brain arteriovenous malformation
- Associated unruptured aneurysm requiring treatment within 3 months
- History of intracranial hemorrhage within the past 6 months
- 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 ≥
- 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
- 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) 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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
プラセボコンパレーター：プラセボ
|
Patients with a low grade aSAH receiving placebo.
Placebo will consist of tablets identical to ticagrelor ones, administered orally with a loading dose of 2 tablets, followed by 1 tablet twice a day during 2 weeks
|
|
実験的：ティカグレル
|
Patients with a low grade aSAH receiving ticagrelor.
Ticagrelor will be administered orally just before the endovascular treatment of the ruptured aneurysm with a loading dose of 180mg, followed by 90 mg twice a day during 2 weeks.
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Effect of tricagrelor on the ischemic complications: peri-procedural thromboembolic events
時間枠：24 hours
|
It will be assessed by the occurence of symptomatic and asymptomatic peri-procedural thromboembolic events within the first 24 hours after the procedure. These events can be :
|
24 hours
|
|
Effect of tricagrelor on the ischemic complications: neurological deterioration
時間枠：14 days
|
It will be assessed by the occurence of neurological deterioration due to delayed cerebral ischemia DCI within 14 days of the endovascular treatment. It will be caracterized by a worsening deficit (≥2 points on NIHSS scale from the previous evaluation), lasting at least 2 hours, not attributed to other causes. |
14 days
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Peri-procedural asymptomatic and symptomatic TEE: angiographic
時間枠：24 hours
|
It will be assessed by the occurence of one peri-procedural angiographic TEE that is, any event with clotting near the neck of the aneurysm or in distal branches and parent vessel occlusion in any vascular territory during procedure within 24 hours of aneurysmal treatment.
|
24 hours
|
|
Peri-procedural asymptomatic and symptomatic TEE: clinical
時間枠：24 hours
|
It will be assessed by the occurence of at least one peri-procedural clinical TEE that is, symptomatic ischemic lesions defined by a worsening ≥2pts on NIHSS from baseline, not attributable to other causes within 24 hours of aneurysmal treatment.
|
24 hours
|
|
Peri-procedural asymptomatic and symptomatic TEE: ischemic lesion
時間枠：24 hours
|
It will be assessed by the occurence of at least one severe symptomatic ischemic lesion defined by worsening >4 points on NIHSS from baseline within 24 hours after the aneurysmal treatment.
|
24 hours
|
|
Peri-procedural asymptomatic and symptomatic TEE: imaging
時間枠：24 hours
|
It will be assessed by the occurence of at least one peri-procedural TEE that is, acute infarctus on MRI performed within 24 hours after endovascular treatment.
|
24 hours
|
|
Neurological deterioration and asymptomatic lesions on MRI due to DCI
時間枠：15 days
|
It will be assessed by the occurence of at least one neurological deterioration due to DCI (worsening ≥2pts on NIHSS compared with previous evaluation), lasting at least 2 hrs, not attributed to other causes after a brain imaging at day 15.
|
15 days
|
|
Neurological deterioration and asymptomatic lesions on MRI due to DCI: severe neurological deterioration
時間枠：15 days
|
It will be assessed by the occurence of at least one severe neurological deterioration due to DCI defined by worsening >4 points on NIHSS compared to previous evaluation, at day 15.
|
15 days
|
|
Neurological deterioration and asymptomatic lesions on MRI due to DCI: asymptomatic MRI lesions
時間枠：15 days
|
It will be assessed by the occurence of new infarctus on MRI at day 15.
|
15 days
|
|
Neurological deterioration and asymptomatic lesions on MRI due to DCI: ischemic event
時間枠：15 days
|
It will be assessed by the occurence of at least one ischemic event (clinical/MRI) related to DCI, at day 15.
|
15 days
|
|
Total incidence of ischemic events per patient
時間枠：15 days
|
It will be assessed by the combined incidence of all ischemic events: sum of both type of ischemic events (related to TEE and/or DCI) at day 15.
|
15 days
|
|
Need for rescue therapy during embolization and/or DCI
時間枠：14 days
|
It will be assessed by the rate of rescue therapy for angiography defined by any mechanical maneuvers (catheter aspiration, stentrievers use or any pharmacological intra-arterial or intravenous therapies) within 14 days of treatment.
|
14 days
|
|
Aneurysm occlusion
時間枠：3 months
|
It will be assessed by the quality of the aneurysm occlusion evaluated at procedure completion, 24 hours and 3 months MRI/MRA based on the Raymond-Roy classification. The Raymond-Roy classification is an angiographic classification used to describe the degree of aneurysm occlusion:
|
3 months
|
|
Clinical outcome at 3 months: good functionnal outcome (disability and functional dependence)
時間枠：3 months
|
It will be assessed by the Modified Rankin Scale (mRS) with a score that must be below 3. It is a clinical scale that measures a patient's degree of disability and functional dependence on a scale from 0 to 6 (the higher the score, the greater the disability and dependence). It will be performed at visit 16 (3 months). |
3 months
|
|
Clinical outcome at 3 months: good functional outcome (disability and recovery)
時間枠：3 months
|
It will be assessed by the GOSE (Glasgow Outcome Scale-Extended) with a score that must be above 5. It is a scale used to assess the level of recovery and disability following a brain injury; it has 8 levels, ranging from 1 (death) to 8 (good recovery). It will be performed at visit 16 (3 months). |
3 months
|
|
Clinical outcome at 3 months: quality of life
時間枠：3 months
|
It will be assessed by the EQ-5D questionnaire at visit 16 (3 months).
It is a health-related quality of life questionnaire that assesses five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression.
Each item is rated on a 5-point scale, resulting in a total score ranging from 1 to 100, where 0 represents the worst possible health status and 100 represents the best.
|
3 months
|
|
Clinical outcome at 3 months: cognitive deterioration
時間枠：3 months
|
The rate of cognitive deterioration will be defined by a MoCA score below or equal to 25, performed at visit 16 (3 months). The MoCA (Montreal Cognitive Assessment) is a screening test for cognitive disorders that yields a score ranging from 0 to 30 (where 0 indicates severely impaired cognitive function and 30 indicates optimal performance). |
3 months
|
|
Clinical outcome at 3 months: deaths
時間枠：3 months
|
It will be assessed by the number of deaths occuring during the totality of the research (3 months).
|
3 months
|
|
Occurence of adverse events
時間枠：3 months
|
All adverse events during the totality of the research (3 months) will be collected.
|
3 months
|
協力者と研究者
捜査官
- 主任研究者：Lionel Calvière、Toulouse Hospital University
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- RC31/23/0369
- 2023 (米国 NIH グラント/契約：GRAMMY Museum Foundation)
- 2023-509795-42-00 (その他の識別子：ID-RCB)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。