Levosimendan in Cardiac Arrest: A Randomized Double-blinded Clinical Phase II Trial (LeICA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Karolinska University Hospital

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

14 Apr 2026 → ongoing

Decision date (initial)

2025-06-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Region Stockholm · Swedish Medical Society · Swedish Heart and lung foundation

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

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.

Secondary objectives 1

1. The effect of levosimendan in comparison to placebo in OHCA on: • Conversion to potentially perfusing rhythm (except VT) among patients without potentially perfusing rhythm at study start • Any ROSC (i.e. return of spontaneous pulse or blood pressure as determined by the treating clinician) • Transport to hospital • Survived event (i.e. ROSC sustained until arrival at the emergency department and transfer of care to medical staff at the receiving hospital) • Sustained ROSC (i.e. ≥20 min of uninterrupted spontaneous pulse or blood pressure as determined by the treating clinician) • Time to sustained ROSC • Hospital arrival status (i.e. subject’s condition at hospital arrival; ROSC, CPR in progress, deceased) • 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) • Number and duration of inotrope infusions (duration >1 h) in the ICU up to 72 hours (e.g. epinephrine, dobutamine, milrinone, levosimendan) • Mechanical circulatory support in the ICU within 7 days (e.g. veno-arterial extracorporeal membrane oxygenation [VA-ECMO], Impella® device, intra-aortic balloon pump) • Organ dysfunction (e.g. renal, hepatic, cardiac) • Neurological outcome at discharge (i.e. cerebral performance category) (1–2 or 3–5) • Circumstances of death • Plasma concentration of levosimendan (intervention group); undetectable plasma concentration of levosimendan (control group) (during initial 72 hours in the intensive care unit). •Organ donation (i.e. ≥1 solid organ donated for transplantation)

Conditions and MedDRA coding

Cardiac arrest

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Witnessed OHCA
2. Prompt start of CPR (within 2 minutes)
3. First recorded rhythm VF or pVT, or PEA in case of suspected pulmonary embolism (as determined by the attending physician)
4. Refractory cardiac arrest, i.e. sustained beyond third rhythm check
5. Intravenous access
6. Age 18-75 years

Exclusion criteria 6

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 severe neurological or systemic disease (e.g. severe dementia, current advanced malignancy, advanced cardiac or pulmonary disease, terminal chronic kidney disease on dialysis)
6. Known pre-existing (i.e. current) DNACPR decision

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Survival at day 30 (binary)

Secondary endpoints 15

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)
9. Number and duration of inotrope infusions (duration >1 h) in the ICU up to 72 hours (e.g. epinephrine, dobutamine, milrinone, levosimendan)
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 (intervention group); undetectable plasma concentration of levosimendan (control group) (during initial 72 hours in the intensive care unit) (binary)
15. Organ donation (i.e. ≥1 solid organ donated for transplantation) (binary)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Karolinska University Hospital

Sponsor organisation

Karolinska University Hospital

Address

Eugeniavagen 3

City

Solna

Postcode

171 64

Country

Sweden

Scientific contact point

Organisation

Karolinska University Hospital

Contact name

Malin Jonsson Fagerlund

Public contact point

Organisation

Karolinska University Hospital

Contact name

Malin Jonsson Fagerlund

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications