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遅発性脳虚血を予防するためのミルリノンによる脳血行動態の最適化 (OPTIMIL)

2026年11月4日 更新者：University Hospital, Toulouse

Efficacy of 10 Days Intravenous Milrinone Treatment to Optimize Cerebral Hemodynamic and Prevent Delayed Cerebral Ischemia (DCI) in Patients With Severe Subarachnoid Hemorrhage Due to Intracranial Aneurysm Rupture

The present study is a randomized, multi-center, double-blind, prospective study that tests the efficacy of intravenous milrinone to optimize cerebral hemodynamic and prevent delayed cerebral ischemia (DCI) during the high-risk period (day 4- day 14) in patients with severe subarachnoid hemorrhage due to intracranial aneurysm rupture (SAHa) (WFNS IV-V). The main objective is to evaluate, in comatose patients and / or sedated on D3 following a severe SAHa (WFNS IV -V), the effect of 10 days of milrinone versus placebo, in addition to the usual management, on the volume of DCI lesions measured on CT scan at 1 month.

調査の概要

状態

積極的、募集していない

条件

介入・治療

詳細な説明

After SAHa, approximately 28% of patients will present DCI. DCI is a major cause of death and disability and will condition the neurological prognosis. Its treatment is not really codified, because of the absence of scientific proof of good level. Milrinone, an inhibitor of type III phosphodiesterase, seems particularly interesting in the management of DCI. This molecule has indeed a powerful vasodilator action. In addition, its anti-inflammatory effects could inhibit the abnormal proliferation of vascular smooth muscle cells and the remodelling observed in patients with DCI via an action on interleukin-6. Finally, because of its positive inotropic effect, it is an interesting choice in these patients with neurogenic cardiomyopathy where the administration of catecholamines is to be avoided. Strong evidence for efficacy of milrinone in the treatment and / or prevention of DCI is still lacking. All patients will benefit from a computed tomography (CT) brain imaging at 48 hrs following aneurysm treatment to define baseline imaging. The standard care (SC) group will follow the recommended management of SAHa and will receive a placebo (intravenous glucose 5%) from day 4 to day 14. The milrinone (M) group will receive, in addition to standard care, administration of milrinone (0.75 μg / kg / min, intravenous) from day 4 to day 14. In case of suspicion of vasospasm and after ineffective effect of medical measures (euvolemia and increase in mean arterial pressure), an endovascular treatment will be possible. The occurrence of vasospasm will be monitored closely with clinical examination and cerebral tissue oxygen pressure (PtiO2). From day 4 to day 14, general and biological data, clinical examination will be collected daily. Intensive care unit complications (neurologic, pulmonary, cardiac and septic complications) will be collected. At 1 month, the volume of DCI lesions will be measured on CT scan. Neurologic prognosis, quality of life and mortality will be studied at 1 month, 3 month, 6 month and 1 year. Adverse events will be monitored closely.

研究の種類

介入

入学 (推定)

234

段階

  • フェーズ2

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究場所

  • フランス
      • Bordeaux、フランス
        • University Hospital Bordeaux
      • Grenoble、フランス
        • CHUGA
      • La Réunion、フランス
        • University Hospital of La Réunion
      • Lyon、フランス
        • HCL
      • Toulouse、フランス
        • University Hospital of Toulouse

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年歳以上 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

Inclusion Criteria:

  • patients with severe SAHa (WFNS IV and V,) whose neurological examination is impossible because of coma (Glasgow coma score of 8 or less) or need for sedation at D3
  • absence of pre-existing neurological handicap (mRS 0-2)
  • major patient (≥ 18 years)
  • affiliation to social security or benefiting through a third person
  • free patient, without tutorship or curatorship or under judicial protection
  • obtaining a signed informed consent by a relative (or the person of trust) after clear and fair information about the study.

Exclusion Criteria:

  • patients with non-severe SAHa (WFNS I, II and III)
  • Occurrence of a major complication (haemorrhagic or ischaemic) documented during the procedure of securing the aneurysm and endangering the short-term vital prognosis
  • heart failure requiring inotropic administration at the time of randomization
  • ICHT at the time of randomisation (ICP> 25 mmHg for at least 20 min)
  • known severe obstructive heart diseases
  • flutter patient or atrial fibrillation
  • hypotension and / or severe hypovolemia with hemodynamic instability
  • septic shock
  • acute / chronic renal insufficiency (Cl <50ml / min)
  • major hydroelectrolytic disorders (hypokalemia <3 mmol / L)
  • known hypersensitivity to milrinone or any of the excipients
  • early limitation of life-sustaining care
  • pregnancy, breastfeeding
  • permanent contraindications to MRI
  • participation in another clinical interventional study

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

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：4倍

武器と介入

参加者グループ / アーム
介入・治療
実験的：Milrinone

"milrinone" group benefiting from an identical treatment to the standard care group and in addition, administration of milrinone (0.75 μg / kg / min, intravenous) from Day 4 to Day 14. In case of suspicion of vasospasm and after ineffective effect of medical measures (euvolemia and increase in mean arterial pressure), an endovascular treatment will be possible. The occurrence of vasospasm will be monitored closely with clinical examination and cerebral tissue oxygen pressure (PtiO2). From D4 to D14, general and biological data, clinical examination will be collected daily. Intensive care unit complications (neurologic, pulmonary, cardiac and septic complications) will be collected. At 1 month, the volume of DCI lesions will be measured on CT scan. Neurologic prognosis, quality of life and mortality will be studied at 1 month, 3 month, 6 month and 1 year. Adverse events will be monitored closely.
薬：Milrinone Injection

administration of milrinone (0.75 μg / kg / min, intravenous) from Day 4 to Day 14
プラセボコンパレーター：Standard Care

The standard care group will follow the recommended management of SAHa and will receive a placebo (intravenous glucose 5%) from Day 4 to Day 14. In case of suspicion of vasospasm and after ineffective effect of medical measures (euvolemia and increase in mean arterial pressure), an endovascular treatment will be possible. The occurrence of vasospasm will be monitored closely with clinical examination and cerebral tissue oxygen pressure (PtiO2). From D4 to D14, general and biological data, clinical examination will be collected daily. Intensive care unit complications (neurologic, pulmonary, cardiac and septic complications) will be collected. At 1 month, the volume of DCI lesions will be measured on CT scan. Neurologic prognosis, quality of life and mortality will be studied at 1 month, 3 month, 6 month and 1 year. Adverse events will be monitored closely.
他の：Placebo

administration of placebo (intravenous glucose 5%) from Day 4 to Day 14

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
volume of delayed cerebral ischemia lesions
時間枠：1 month

volume of DCI lesions measured on CT scan and validated by Magnetic Resonance Imaging (MRI) imaging at 1 month
1 month

二次結果の測定

結果測定
メジャーの説明
時間枠
Radiological parameters on CT at 1 month
時間枠：1 month

percentage of patients with DCI lesions
1 month
Evolution in intensive care: Neurological complications 1
時間枠：1 month

number of episodes of PtiO2 below the ischemic threshold in intensive care: PtiO2 <20 mmHg (moderate hypoxia) and <15 mm Hg (severe hypoxia) for at least 15 minutes
1 month
Evolution in intensive care: Neurological complications 2
時間枠：1 month

total duration of episodes of PtiO2 <20 mm Hg (moderate hypoxia) and <15 mm Hg (severe hypoxia)
1 month
Evolution in intensive care: Neurological complications 3
時間枠：1 month

number of recourse to an endovascular treatment
1 month
Evolution in intensive care: Neurological complications 4
時間枠：1 month

intracranial hypertension in intensive care: ICP> 20 mmHg for at least 15 minutes.
1 month
Number and type of non-neurological complications
時間枠：1 month

non-neurological complications
1 month
Number of days in intensive care
時間枠：1 month

Number of days in intensive care
1 month
Number of days with mechanical ventilation
時間枠：1 month

Number of days with mechanical ventilation
1 month
neurological prognosis at 1 month: Rankin score
時間枠：1 month

evaluated by the modified Rankin score (good prognosis: mRS 0, 1 and 2 / poor prognosis: mRS 3, 4 and 5)
1 month
neurological prognosis at 1 month: Glasgow Outcome scale
時間枠：1 month

evaluated by the Glasgow Outcome Scale (GOS) (good prognosis: GOS 4 and 5 / poor prognosis: GOS 1, 2 and 3).
1 month
neurological prognosis at 3 month: Rankin score
時間枠：3 month

evaluated by the modified Rankin score (good prognosis: mRS 0, 1 and 2 / poor prognosis: mRS 3, 4 and 5)
3 month
neurological prognosis at 3 month: Glasgow Outcome scale
時間枠：3 month

evaluated by the the Glasgow Outcome Scale (good prognosis: GOS 4 and 5 / poor prognosis: GOS 1, 2 and 3)
3 month
neurological prognosis at 6 month: Rankin score
時間枠：6 month

evaluated by the modified Rankin score (good prognosis: mRS 0, 1 and 2 / poor prognosis: mRS 3, 4 and 5)
6 month
neurological prognosis at 6 month: Glasgow Outcome scale
時間枠：6 month

evaluated by the the Glasgow Outcome Scale (good prognosis: GOS 4 and 5 / poor prognosis: GOS 1, 2 and 3)
6 month
neurological prognosis at 1 year: Rankin score
時間枠：1 year

evaluated by the modified Rankin score (good prognosis: mRS 0, 1 and 2 / poor prognosis: mRS 3, 4 and 5)
1 year
neurological prognosis at 1 year: Glasgow Outcome scale
時間枠：1 year

evaluated by the Glasgow Outcome Scale (good prognosis: GOS 4 and 5 / poor prognosis: GOS 1, 2 and 3)
1 year
Mortality at 1 month
時間枠：1 month

Mortality at 1 month
1 month
Mortality at 3 month
時間枠：3 month

Mortality at 3 month
3 month
Mortality at 6 month
時間枠：6 month

Mortality at 6 month
6 month
Mortality at 1 year
時間枠：1 year

Mortality at 1 year
1 year
number of days of hospitalization
時間枠：1 year

number of days of hospitalization
1 year

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

University Hospital, Toulouse

捜査官

  • 主任研究者：Thomas Geeraerts, MD PhD、University Hospital, Toulouse

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2021年7月25日

一次修了 (推定)

2027年7月1日

研究の完了 (推定)

2027年7月1日

試験登録日

最初に提出

2020年2月17日

QC基準を満たした最初の提出物

2020年2月20日

最初の投稿 (実際)

2020年2月25日

学習記録の更新

投稿された最後の更新 (実際)

2026年11月9日

QC基準を満たした最後の更新が送信されました

2026年11月4日

最終確認日

2026年11月1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

  • RC31/18/0472

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?

いいえ

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

いいえ

米国FDA規制機器製品の研究

いいえ

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