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Levosimendan as Treatment of Aneurysmal SubArachnoid Haemorrhage (LEVOSAH)

Primary Purpose

Sub-arachnoid Haemorrhage

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Levosimendan
Placebo
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sub-arachnoid Haemorrhage focused on measuring Sub-arachnoid haemorrhage, vasospasm, delayed cerebral ischemia, stroke

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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. Exclusion Criteria: 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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    LEVOSIMENDAN

    PLACEBO

    Arm Description

    Experimental : Levosimendan group

    Placebo : Comparator group

    Outcomes

    Primary Outcome Measures

    SAFETY / TOLERABILITY / EFFICACY
    Proportion of patients with at least one of the following: death, vasopasm, or DCI 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

    Secondary Outcome Measures

    Full Information

    First Posted
    July 28, 2022
    Last Updated
    December 16, 2022
    Sponsor
    Assistance Publique - Hôpitaux de Paris
    Collaborators
    Orion Corporation, Orion Pharma
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05664191
    Brief Title
    Levosimendan as Treatment of Aneurysmal SubArachnoid Haemorrhage
    Acronym
    LEVOSAH
    Official Title
    Use of Levosimendan as Treatment of Aneurysmal SubArachnoid Hemorrhage
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    December 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    March 1, 2023 (Anticipated)
    Primary Completion Date
    March 1, 2024 (Anticipated)
    Study Completion Date
    March 1, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Assistance Publique - Hôpitaux de Paris
    Collaborators
    Orion Corporation, Orion Pharma

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    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
    Detailed Description
    Background Aneurysmal subarachnoid hemorrhage (aSAH) is a frequent type of stroke. It is associated with a significant morbidity and mortality and particularly affects young subjects. Complications that can occur after an aSAH include acute cardiac dysfunction and cerebral arterial vasospasm (CVS), which produces delayed cerebral ischemia (DCI). These complications are associated with a worsened outcome for aSAH patients. There is no proven preventive treatment for these complications. Clinical and experimental data show that Levosimendan could be ideal to prevent these complications. In a recent study (Trinh-Duc et al, Crit Care 2021), treatment with Levosimendan was associated with a reduced incidence of CVS in a SAH patients. The use of levosimendan, a non-catecholaminergic vasodilator inotrope in a context of already maximal endogenous adrenergic stimulation, thus seems to be suitable and able to improve the prognosis of aSAH patients. Experimental design Single-center, phase II, comparative, randomized, superiority, placebo-controlled, double-blind, pilot drug trial using Bayesian inference. Study drug Patient treated with levosimendan infusion at 0.1 microgram/kg/min for 24 hours at D1 and D8. Number of patients 30 patients, i.e. 15 patients per group Number of centre : 1 Duration of inclusion: 24 months Total duration of the trial: 27 months Statistical analysis Primary endpoint: The proportion of patients with at least one of the following: death, vasopasm, or DCI within 14 days of inclusion will be compared using Bayesian analysis. Secondary endpoints: Qualitative secondary endpoints will be analyzed by Chi-2 test. An exact probability test will be used if the Chi-2 validity criteria are not met. Quantitative secondary endpoints will be compared by Student's t test. Qualitative secondary endpoints will be compared by Wilcoxon test The evolution of mortality will be compared using a log-rank test The tests will be two-sided at the 5% significance level. Support This study is supported by Assistance Publique - Hôpitaux de Paris (AP-HP) and Orion Pharma.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Sub-arachnoid Haemorrhage
    Keywords
    Sub-arachnoid haemorrhage, vasospasm, delayed cerebral ischemia, stroke

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Masking Description
    Double blind
    Allocation
    Randomized
    Enrollment
    30 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    LEVOSIMENDAN
    Arm Type
    Experimental
    Arm Description
    Experimental : Levosimendan group
    Arm Title
    PLACEBO
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo : Comparator group
    Intervention Type
    Drug
    Intervention Name(s)
    Levosimendan
    Intervention Description
    Infusion at 0.1 µg/kg/min at day 1 and day 8
    Intervention Type
    Other
    Intervention Name(s)
    Placebo
    Intervention Description
    Glucose 5%, solution for injection ECOFLAC at day 1 and day 8
    Primary Outcome Measure Information:
    Title
    SAFETY / TOLERABILITY / EFFICACY
    Description
    Proportion of patients with at least one of the following: death, vasopasm, or DCI within 14 days of inclusion.
    Time Frame
    within 14 days of inclusion
    Title
    SAFETY / TOLERABILITY / EFFICACY
    Description
    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
    Time Frame
    day 14, day 28, day 90

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    75 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: 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. Exclusion Criteria: 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
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Benjamin Glen Chousterman
    Phone
    01.49.95.85.15
    Ext
    +33
    Email
    Benjamin.chousterman@aphp.fr
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Benjamin Glen Chousterman
    Organizational Affiliation
    Hôpital Lariboisière
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    34784938
    Citation
    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.
    Results Reference
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    Levosimendan as Treatment of Aneurysmal SubArachnoid Haemorrhage

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