Objective: Safety and efficacy of low-dose prostacyclin administration and blood pressure target in addition to standard therapy, as compared to standard therapy alone, in post-cardiac-arrest-syndrome (PCAS) patients.

Trial Rationale: Therapeutic interventions directed towards the damaged endothelium may improve outcome for patients with PCAS. Prostacyclin/Iloprost (PGI2) is an endogenous prostanoid which is formed and released by endothelial cells with anti-platelet, vasodilatory and cytoprotective properties36 and is expected to be beneficial by protecting and deactivating the endothelium and by restoring vascular integrity in patients suffering from endothelial breakdown.

Trial Population: Participants in the trial must be adult patients (≥18 years of age) with out-of-hospital cardiac arrest (OHCA) of presumed cardiac cause admitted to the Dept. of Cardiology, 2143, Rigshospitalet, Copenhagen.

Trial Design: Randomized, placebo controlled, double-blind investigator-initiated trial in 40 OHCA patients. 48 hours of active study drug (Iloprost, 1 ng/kg/min) versus placebo (saline) infusion.

Patients in both randomization groups will be treated in accordance with state-of-the art therapy including targeted temperature management. Interventions are considered emergency procedures and study drug infusion should be commenced as soon as possible after sustained return of spontaneous circulation (ROSC), screening and randomization.

Patients will only be enrolled after informed consent, but as the treatment has to be initiated earliest possible after the out of hospital cardiac arrest diagnosis i.e., at a time-point where patients are temporarily incompetent, scientific guardians will co-sign the informed consent form before inclusion. Next-of-kin and the patients' general practitioner will co-sign as soon as possible and the patient will provide informed consent whenever possible.

During the study, blood samples will be taken at different time points. Patients will be observed and assessed continuously with regards to complications including bleeding. Patients will be actively assessed as long as the patient is in the ICU. During the extended follow up period at day 30, 90 and 180 contact will be made with the patients to follow up on safety events and vital status.

The trial is conducted in accordance with the protocol and is approved by Danish health and medicines authority, Danish ethics committee and danish data protection agency.

Investigational product: The active treatment in the trial is 1 ng/kg/min Ilomedin® administered as a 48h continuous i.v infusion. The drugs will be administered according to the product specifications.

Placebo: The placebo is 0.9% saline administered as a 48h continuous i.v infusion. The i.v volume of placebo saline to be administered is equal to the administered volume of diluted (in 0.9% saline) active drug.

Sponsor of study and financial support: This research project is investigator-initiated by the trial Sponsor Pär I. Johansson in collaboration with the principal investigator Christian Hassager.

It has not received funding from any commercial sponsors.

Patient recruitment period runs from February 2016 to August 2016. Follow-up data on 30-day, 90-day and 180-day outcome and adverse events will be collected. Initial data analyses will be done after completion of 30-day follow-up for all patients. Secondary data analyses will be done after completion of 180-day follow-up for all patients.

Inclusion Criteria:

1. Age ≥18 years
2. OHCA of presumed cardiac cause
3. Sustained ROSC*
4. Unconsciousness (GCS <8) (patients not able to obey verbal commands) after sustained ROSC*
5. Target temperature management is indicated.

Exclusion Criteria:

1. Conscious patients (obeying verbal commands)
2. Females of childbearing potential (unless a negative human chorionic gonadotropin (HCG) test can rule out pregnancy within the inclusion window)
3. Patients weighing more than 135kg
4. In-hospital cardiac arrest (IHCA)
5. OHCA of presumed non-cardiac cause, e.g. after trauma or dissection/rupture of major artery OR Cardiac arrest caused by initial hypoxia (i.e. drowning, suffocation, hanging).
6. Known congenital bleeding diathesis (medically induced coagulopathy due to treatment with Vitamin K antagonists, Thrombininhibitors, Factor Xa inihbitors, ADP-receptor inhibitors, Aspirin, Asasantin, Persantin, NSAID, unfractionated and low molecular weight heparin does NOT exclude the patient).
7. Suspected or confirmed acute intracranial bleeding
8. Suspected or confirmed acute stroke
9. Unwitnessed asystole
10. Known limitations in therapy and Do Not Resuscitate-order
11. Known disease making 180 days survival unlikely
12. Known pre-arrest CPC 3 or 4
13. >4 hours (240 minutes) from ROSC to screening
14. Systolic blood pressure <80 mm Hg in spite of fluid loading/vasopressor and/or inotropic medication/intra-aortic balloon pump/axial flow device*
15. Temperature on admission <30°C.
16. Known allergy to Prostacyclin analogues