Levosimendan in out of hospital cardiac arrest

ISRCTN	ISRCTN15862521
DOI	https://doi.org/10.1186/ISRCTN15862521
EudraCT/CTIS number	2024-517279-20-02

Submission date: 21/10/2025
Registration date: 22/10/2025
Last edited: 22/10/2025

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 ID	0000-0002-8341-6700
Phone	+46 812372107
Email	malin.jonsson-fagerlund@regionstockholm.se

Study information

Study design	Phase II investigator-initiated randomized parallel-group placebo-controlled double-blinded pilot trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital, Internet/virtual, Other
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details below to request a participant information sheet
Scientific title	Levosimendan in Cardiac Arrest: a randomized double-blinded clinical phase II trial (LeICA)
Study acronym	LeICA
Study objectives	The 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) studied	Out-of-hospital cardiac arrest
Intervention	The 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 type	Drug
Pharmaceutical study type(s)	Treatment study
Phase	Phase II
Drug / device / biological / vaccine name(s)	Levosimendan
Primary outcome measure	Survival at day 30 (binary) measured using patient records
Secondary outcome measures	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)
Overall study start date	11/06/2025
Completion date	31/07/2027

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Upper age limit	75 Years
Sex	Both
Target number of participants	40
Key inclusion criteria	1. 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 criteria	1. 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 enrolment	15/01/2026
Date of final enrolment	31/07/2026

Locations

Countries of recruitment

Sweden

Study participating centres

Karolinska University Hospital

Eugeniavägen 3
Stockholm
17176
Sweden

AISAB

Box 90219
Stockholm
12023
Sweden

Sponsor information

Karolinska University Hospital
Hospital/treatment centre

Eugeniavägen 3
Stockholm
17176
Sweden

"ROR"	https://ror.org/00m8d6786

Funders

Funder type

Charity

Hjärt-Lungfonden
Private sector organisation / Trusts, charities, foundations (both public and private)

Alternative name(s): Swedish Heart-Lung Foundation
Location: Sweden

Region Stockholm

No information available

Svenska Läkaresällskapet
Private sector organisation / Other non-profit organizations

Alternative name(s): Swedish Society of Medicine, Swedish Medical Society, SLS
Location: Sweden

Karolinska Institutet
Government organisation / Local government

Alternative name(s): Karolinska Institute, KI
Location: Sweden

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
Publication and dissemination plan	Planned publication in a peer-reviewed journal
IPD sharing plan	Not provided at time of registration

Editorial Notes

22/10/2025: Study's existence confirmed by the Swedish Medical Products Agency.