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Cerebral hemodynamisk optimering av Milrinone för att förhindra fördröjd cerebral ischemi (OPTIMIL)

4 november 2026 uppdaterad av: 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.

Studieöversikt

Status

Aktiv, inte rekryterande

Betingelser

Intervention / Behandling

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Beräknad)

234

Fas

  • Fas 2

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

  • Frankrike
      • Bordeaux, Frankrike
        • University Hospital Bordeaux
      • Grenoble, Frankrike
        • CHUGA
      • La Réunion, Frankrike
        • University Hospital of La Réunion
      • Lyon, Frankrike
        • HCL
      • Toulouse, Frankrike
        • University Hospital of Toulouse

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år och äldre (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Fyrdubbla

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: 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.
Läkemedel: Milrinone Injection

administration of milrinone (0.75 μg / kg / min, intravenous) from Day 4 to Day 14
Placebo-jämförare: 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.
Övrig: Placebo

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

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
volume of delayed cerebral ischemia lesions
Tidsram: 1 month

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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Radiological parameters on CT at 1 month
Tidsram: 1 month

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

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

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

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

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

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

Mortality at 1 month
1 month
Mortality at 3 month
Tidsram: 3 month

Mortality at 3 month
3 month
Mortality at 6 month
Tidsram: 6 month

Mortality at 6 month
6 month
Mortality at 1 year
Tidsram: 1 year

Mortality at 1 year
1 year
number of days of hospitalization
Tidsram: 1 year

number of days of hospitalization
1 year

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Sponsor

University Hospital, Toulouse

Utredare

  • Huvudutredare: Thomas Geeraerts, MD PhD, University Hospital, Toulouse

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

25 juli 2021

Primärt slutförande (Beräknad)

1 juli 2027

Avslutad studie (Beräknad)

1 juli 2027

Studieregistreringsdatum

Först inskickad

17 februari 2020

Först inskickad som uppfyllde QC-kriterierna

20 februari 2020

Första postat (Faktisk)

25 februari 2020

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

9 november 2026

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

4 november 2026

Senast verifierad

1 november 2026

Mer information

Termer relaterade till denna studie

Nyckelord

Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • RC31/18/0472

Plan för individuella deltagardata (IPD)

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NEJ

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