Sub-arachnoid HaemorrhagePhase 2LEVOSAHNCT05664191
Levosimendan as Treatment of Aneurysmal SubArachnoid Haemorrhage
A Phase 2 study testing Levosimendan in people with Sub-arachnoid Haemorrhage, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Sub-arachnoid Haemorrhage
- What is being tested?
- Levosimendan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- 13 Oct 2023to 13 Apr 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- Moribund patients.
- Patient not affiliated to social security
- Patient participating in another interventional research
- Patients under legal guardianship or curatorship
Trial locations and contacts
1 site in 1 country.
France1 site
Hôpital Lariboisière, Service d'anesthésie Réanimation
Paris, France, 75010
About this study
Official title: Use of Levosimendan as Treatment of Aneurysmal SubArachnoid Hemorrhage
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.
Read more
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
Read the 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.
- Conditions
- Sub-arachnoid Haemorrhage
- Being tested
- Levosimendan, Placebo
- Keywords
- Sub-arachnoid haemorrhage, vasospasm, delayed cerebral ischemia, stroke
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevosimendanDrug
Infusion at 0.1 µg/kg/min at day 1 and day 8
PlaceboOther
Glucose 5%, solution for injection ECOFLAC at day 1 and day 8
| Study group | Role | What they receive |
|---|---|---|
| LEVOSIMENDAN | Experimental | Experimental : Levosimendan group Receives: Drug: Levosimendan |
| PLACEBO | Placebo comparator | Placebo : Comparator group Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
SAFETY / TOLERABILITY / EFFICACY
Proportion of patients with at least one of the following: death, vasopasm, or DCI within 14 days of inclusion.
Measured: 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
Measured: day 14, day 28, day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2022
- Study start13 Oct 2023
- Primary completion13 Apr 2026
- Study completion13 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Sub-arachnoid HaemorrhageStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Orion Corporation, Orion Pharma
- Responsible party
- Sponsor
- Investigators
- Benjamin Glen Chousterman, Study director, Hopital Lariboisière
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05664191
- Sponsor's protocol ID
- APHP200175
- Acronym
- LEVOSAH
- Status last verified
- Aug 2026
- First submitted
- 28 Jul 2022
- Last updated
- 31 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34784938
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Use of Levosimendan as Treatment of Aneurysmal SubArachnoid Hemorrhage
- ClinicalTrials.gov ID
- NCT05664191
- Acronym / sponsor ID
- LEVOSAH / APHP200175
- Conditions
- Sub-arachnoid Haemorrhage
- Keywords
- Sub-arachnoid haemorrhage, vasospasm, delayed cerebral ischemia, stroke
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Orion Corporation, Orion Pharma
- Study start
- 13 Oct 2023 (actual)
- Primary completion
- 13 Apr 2026 (actual)
- Study completion
- 13 Apr 2026 (actual)
- First posted
- 23 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| LEVOSIMENDAN | Experimental | Drug: LevosimendanExperimental : Levosimendan group |
| PLACEBO | Placebo comparator | Other: PlaceboPlacebo : Comparator group |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevosimendanInfusion at 0.1 µg/kg/min at day 1 and day 8 | Drug | LEVOSIMENDAN |
| PlaceboGlucose 5%, solution for injection ECOFLAC at day 1 and day 8 | Other | PLACEBO |
Primary outcome
SAFETY / TOLERABILITY / EFFICACY
Time frame: within 14 days of inclusion
Proportion of patients with at least one of the following: death, vasopasm, or DCI within 14 days of inclusion.
SAFETY / TOLERABILITY / EFFICACY
Time frame: day 14, day 28, day 90
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2026.
- Background: PubMed 34784938Trinh-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Benjamin Glen Chousterman study director
Hopital Lariboisière
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Levosimendan in people with Sub-arachnoid Haemorrhage, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
SAFETY / TOLERABILITY / EFFICACY (time frame: within 14 days of inclusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05664191, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.