Levosimendan as Treatment of Aneurysmal SubArachnoid Haemorrhage

NCT05664191 | Recruiting Phase 2 DMC

• 1 other identifier: APHP200175
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Sub-arachnoid haemorrhage (SAH) are often due to ruptured intracerebral aneurysms and are associated with an importante morbi-mortality. SAH are often complicated by delayed cerebral ischemia (DCI) potentially due to cerebral vasospasm (CVS). A recent study showed that levosimendan, an inotropic and vasodilatory drug, could reduce the incidence of CVS and potentially improve patient outcome. In this pilot randomized controlled trial, we will evaluate the impact Levosimendan vs Placebo in SAH patient on the occurrence of CVS and DCI. Study population: adult patient admitted to ICU for aneurysmal SAH WFNS grade I-IV and mFisher 3-4. Intervention: Levosimendan (0.1 µg/kg/min) or placebo infusion at Day 1 and 8. Primary outcome: incidence of DCI or CVS at day 14 Duration of the study: 24 months Number of patients: 30 (15 patients per group) Number of center: 1

Conditions

Sub-arachnoid Haemorrhage

Keywords

Sub-arachnoid haemorrhage; vasospasm; delayed cerebral ischemia; stroke

Outcome Measures

Primary Outcomes (2)

• SAFETY / TOLERABILITY / EFFICACY

  Proportion of patients with at least one of the following: death, vasopasm, or DCI within 14 days of inclusion.

  within 14 days of inclusion

• SAFETY / TOLERABILITY / EFFICACY

  Cumulative incidence of mortality, DCI, and vasospasm mRS score at 3 months Value of peak serum catecholamines (norepinephrine, adrenaline) within 5 days of admission Number of days alive at D14 without catecholamines and maximum dose (norepinephrine, dobutamine, dopamine, adrenaline, isoprenaline) if used. Time to peak troponin and BNP and their values Systolic and diastolic heart function assessed by echocardiography Daily clinical evolution with Glasgow score Daily transcranial doppler evolution Occurrence and extent of secondary cerebral ischemia diagnosed by systematic MRI at 3 months. Length of stay in the intensive care unit

  day 14, day 28, day 90

Study Arms (2)

LEVOSIMENDAN

EXPERIMENTAL

Experimental : Levosimendan group

Drug: Levosimendan

PLACEBO

PLACEBO COMPARATOR

Placebo : Comparator group

Other: Placebo

Interventions

Levosimendan DRUG

Infusion at 0.1 µg/kg/min at day 1 and day 8

LEVOSIMENDAN

Placebo OTHER

Glucose 5%, solution for injection ECOFLAC at day 1 and day 8

PLACEBO

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All adult patients (18 to 75 years old),
• hospitalized in surgical intensive care at Lariboisière Hospital for subarachnoid haemorrhage of aneurysmal origin
• WFNS clinical score of I to IV and a mFisher score of 3 or 4.

You may not qualify if:

• pregnant women
• contraindications to levosimendan (including hypersensitivity to levosimendan, severe hypotension (mean arterial pressure less than 65 mmHg), tachycardia (heart rate greater than 120 bpm), cardiac mechanical obstructions)
• severe renal failure (creatinine clearance \< 30 ml/min)
• severe hepatic failure (signs of hepatic encephalopathy) or chronic liver disease
• history of torsades de pointes
• pre-existing severe neurovascular pathologies.
• Moribund patients.
• Patient not affiliated to social security
• Patient participating in another interventional research
• Patients under legal guardianship or curatorship

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Orion Corporation, Orion Pharma: collaborator

Study Sites (1)

Hôpital Lariboisière, Service d'anesthésie Réanimation

Paris, France, 75010, France

RECRUITING

Related Publications (1)

• Trinh-Duc A, Labeyrie MA, Caillard A, Ben Hassen W, Mebazaa A, Chousterman BG. Effects of levosimendan on occurrence of cerebral vasospasm after aneurysmal subarachnoid hemorrhage: a case-control study. Crit Care. 2021 Nov 16;25(1):396. doi: 10.1186/s13054-021-03824-x. No abstract available.

  PMID: 34784938 BACKGROUND

MeSH Terms

Conditions

Stroke

Interventions

Simendan

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Hydrazones; Hydrazines; Organic Chemicals; Pyridazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Benjamin Glen Chousterman

  Hôpital Lariboisière

  STUDY DIRECTOR

Central Study Contacts

Benjamin Glen Chousterman

CONTACT

01.49.95.85.15; Benjamin.chousterman@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 28, 2022
• First Posted: December 23, 2022
• Study Start: October 13, 2023
• Primary Completion: April 13, 2026
• Study Completion: April 13, 2026
• Last Updated: September 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)