Levosimendan in out of hospital cardiac arrest

ISRCTN ISRCTN15862521
DOI https://doi.org/10.1186/ISRCTN15862521
ClinicalTrials.gov (NCT) Nil known
Clinical Trials Information System (CTIS) 2024-517279-20-02
Protocol serial number Nil known
Sponsor Karolinska University Hospital
Funders Hjärt-Lungfonden, Region Stockholm, Svenska Läkaresällskapet, Karolinska Institutet
Submission date
21/10/2025
Registration date
22/10/2025
Last edited
25/11/2025
Recruitment status
Not yet recruiting
Overall study status
Ongoing
Condition category
Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year

Plain English summary of protocol

Background and study aims
Every year, around 6,000 people in Sweden suffer a cardiac arrest outside of hospital. Sadly, fewer than 1 in 10 survive to leave the hospital. While CPR and defibrillation can help restart the heart, medicines used during resuscitation have not shown much benefit in improving long-term survival. A drug called levosimendan, which helps the heart pump more effectively, has shown promise in early studies. This trial aims to find out whether giving levosimendan during CPR can improve survival 30 days after cardiac arrest. The results will help guide a larger future study focused on survival with good brain function.

Who can participate?
Adults aged 18 to 75 years who have a witnessed cardiac arrest outside of hospital may be eligible. To take part, CPR must begin quickly (within 2 minutes), and the heart rhythm must meet specific criteria. Patients must also have intravenous access. People will not be included if the cardiac arrest is caused by trauma, if the first heart rhythm is asystole, if the drug cannot be given within 30 minutes, or if they have certain serious health conditions or a Do Not Resuscitate order.

What does the study involve?
Eligible patients will be randomly assigned at the scene to receive either levosimendan or a placebo (a dummy treatment) during CPR. The study drug is given as a single dose. The medical team will continue standard resuscitation care. Researchers will then monitor outcomes such as survival, heart function, and neurological status.

What are the possible benefits and risks of participating?
The potential benefit is improved survival and heart function after cardiac arrest. Levosimendan has a good safety profile, but as with any medication, there may be risks or side effects. Because the drug is given during a medical emergency, patients cannot give consent beforehand. However, the study follows strict ethical guidelines to protect participants.

Where is the study run from?
The study is being conducted in the Stockholm region of Sweden.

When is the study starting and how long is it expected to run for?
June 2025 to July 2027

Who is funding the study?
The study is funded by Region Stockholm, the Swedish Heart and Lung Foundation, the Swedish Society for Medicine, and Karolinska Institutet.

who is the main contact?
Prof. Malin Jonsson Fagerlund, malin.jonsson-fagerlund@regionstockholm.se

Contact information

Prof Malin Jonsson Fagerlund
Public, Scientific, Principal investigator

Eugeniavägen 3
Stockholm
17176
Sweden

ORCiD logo 0000-0002-8341-6700
+46 812372107
malin.jonsson-fagerlund@regionstockholm.se

Study information

Primary study designInterventional
Study designPhase II investigator-initiated randomized parallel-group placebo-controlled double-blinded pilot trial
Secondary study designRandomised controlled trial
Scientific titleLevosimendan in Cardiac Arrest: a randomized double-blinded clinical phase II trial (LeICA)
Study acronymLeICA
Study objectivesThe primary objective of this trial is to investigate if a single dose of levosimendan given during cardiopulmonary resuscitation (CPR) for out-of-hospital cardiac arrest (OHCA) increases 30-day survival compared to placebo.

The secondary objective of this trial is to evaluate the clinical efficacy of levosimendan in comparison to placebo.
Ethics approval(s)

Approved 11/06/2025, Swedish Medical Products Agency (PO Box 26, Uppsala, 75103, Sweden; + 46 (0)18 17 46 00; registrator@lakemedelsverket.se), ref: Dnr: 5.1.1-2025-025629

Health condition(s) or problem(s) studiedOut-of-hospital cardiac arrest
InterventionThe randomisation is done using an online randomisation tool.

The intervention is one intravenous bolus injection of levosimendan or placebo during ongoing prehospital CPR.

1. A prefilled, blinded, syringe with 50 ml of study drug: levosimendan 2.5 mg (2.5 mg/ml, 1 ml in 49 ml 5% glucose, total volume 50 ml)
2. A prefilled, blinded, syringe with 50 ml of placebo: 5% glucose (total volume 50 ml)

Standard monitoring and diagnostic equipment will be used according to present guidelines for cardiac arrest and ACL (for example defibrillator, external compressions with LUCAS).

The patients will be followed up in a specific CRF for 30 days and via hospital charts etc for 30 days.
Intervention typeDrug
PhasePhase II
Drug / device / biological / vaccine name(s)Levosimendan
Primary outcome measure(s)

Survival at day 30 (binary) measured using patient records

Key secondary outcome measure(s)

Measured using patient records:
1. Conversion to potentially perfusing rhythm (except VT) among patients without potentially perfusing rhythm at study start (binary)
2. Any ROSC (i.e. return of spontaneous pulse or blood pressure as determined by the treating clinician) (binary)
3. Transport to hospital (binary)
4. Survived event (i.e. ROSC sustained until arrival at the emergency department and transfer of care to medical staff at the receiving hospital) (binary)
5. Sustained ROSC (i.e. ≥20 min of uninterrupted spontaneous pulse or blood pressure as determined by the treating clinician) (binary)
6. Time to sustained ROSC (continuous, numerical)
7. Hospital arrival status (i.e. subject’s condition at hospital arrival; ROSC, CPR in progress, deceased) (categorical)
8. Number and duration of vasopressor infusions (duration >1 h) in the ICU up to 72 hours (e.g. norepinephrine, epinephrine, phenylephrine, vasopressin, dopamine, methylene blue) (continuous)
9. Number and duration of inotrope infusions (duration >1 h) in the ICU up to 72 hours (e.g. epinephrine, dobutamine, milrinone, levosimendan) (continuous)
10. Mechanical circulatory support in the ICU within 7 days (e.g. veno-arterial extracorporeal membrane oxygenation [VA-ECMO], Impella device, intra-aortic balloon pump) (binary)
11. Organ dysfunction (e.g. renal, hepatic, cardiac) (exploratory)
12. Neurological outcome at discharge (i.e. cerebral performance category 1–2 or 3–5) (binary)
13. Circumstances of death (categorical)
14. Plasma concentration of levosimendan (during initial 72 hours in the intensive care unit) (continuous)
15. Organ donation (i.e. ≥1 solid organ donated for transplantation) (binary)

Completion date31/07/2027

Eligibility

Participant type(s)Patient
Age groupMixed
Lower age limit18 Years
Upper age limit75 Years
SexAll
Target sample size at registration40
Key inclusion criteria1. Aged 18-75 years
2. Witnessed OHCA
3. Prompt start of CPR (i.e. within 2 minutes)
4. First recorded rhythm ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT), or pulseless electrical activity (PEA) in case of suspected pulmonary embolism (as determined by the attending physician)
5. Refractory cardiac arrest, i.e. sustained beyond third rhythm check
6. Intravenous access
Key exclusion criteria1. Traumatic cause of cardiac arrest
2. First recorded rhythm asystole
3. Time to administration of study drug >30 min after onset of cardiac arrest
4. Known or apparent pregnancy
5. Known pre-existing advanced malignancy, severe neurological or systemic disease, advanced cardiac or pulmonary disease, terminal chronic kidney disease on dialysis or ongoing bleeding
6. Known pre-existing (i.e. current) Do Not Attempt Cardiopulmonary Resuscitation (DNACPR) decision
Date of first enrolment15/01/2026
Date of final enrolment31/07/2026

Locations

Countries of recruitment

  • Sweden

Study participating centres

Karolinska University Hospital
Eugeniavägen 3
Stockholm
17176
Sweden
AISAB
Box 90219
Stockholm
12023
Sweden

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryData sharing statement to be made available at a later date
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Protocol article 24/11/2025 25/11/2025 Yes No

Editorial Notes

25/11/2025: Publication reference added.
22/10/2025: Study's existence confirmed by the Swedish Medical Products Agency.

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