Endothelial Dysfunction in Resuscitated Cardiac Arrest

NCT02685618 | Completed Phase 2 DMC

• 1 other identifier: 2014092629
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Cardiac Arrest

Outcome Measures

Primary Outcomes (1)

• Mean change i plasma biomarkers reflecting endothelial activation and damage

  Mean change in biomarkers indicative of endothelial activation and damage (sE-selectin, syndecan-1, soluble thrombomodulin (sTM), soluble vascular endothelial growth factor (sVEGF), nucleosomes) and sympathoadrenal overactivation (epinephrine/norepinephrine) from baseline to 48 hours post-randomization.

  48 hours

Secondary Outcomes (3)

• Mean change in hemostatic profile evaluated by TEG, Multiplate, Flowcytometry

  48 hours

• Blood pressure target influence on primary outcomes measured by mean change in plasma biomarkers.

  48 hours

• Feasibility of blood pressure target intervention.

  48 hours

Other Outcomes (7)

• Number of patients with severe bleeding

  24 hours-180 days

• Number of patients requiring organ support

  48 hours to 180 days

• Mean change in disease severity score

  48 to 96 hours

Study Arms (4)

Iloprost + M1006B offset by -10 mmHg

EXPERIMENTAL

Administration of 1 ng/kg/min Ilomedin® as a 48h continuous i.v infusion. Administration of blood pressure modules M1006B: offset by -10 mmHg Intervention: Drug: Iloprost + M1006B offset -10mmHg

Drug: Iloprost; Device: Phillips M1006B, offset by -10mmHg

Iloprost + M1006B, No offset

EXPERIMENTAL

Administration of 1 ng/kg/min Ilomedin® as a 48h continuous i.v infusion Administration of blood pressure modules M1006B: No offset Intervention: Drug: Iloprost + M1006B, No offset

Drug: Iloprost; Device: Philips M1006B, No offset

Placebo + M1006B offset by -10 mmHg

PLACEBO COMPARATOR

Double dummy 0.9% saline as a 48h continuous i.v infusion. Administration of blood pressure modules M1006B: offset by -10 mmHg Intervention: Drug: Placebo + M1006B offset -10mmHg

Drug: Saline; Device: Phillips M1006B, offset by -10mmHg

Placebo + M1006B, No offset

PLACEBO COMPARATOR

Double dummy 0.9% saline as a 48h continuous i.v infusion Administration of blood pressure modules M1006B: No offset Intervention: Drug: Placebo + M1006B, No offset

Drug: Saline; Device: Philips M1006B, No offset

Interventions

Iloprost DRUG

Also known as: Ilomedin (R), Prostacyclin analogue (PGI2)

Iloprost + M1006B offset by -10 mmHg; Iloprost + M1006B, No offset

Saline DRUG

Also known as: 0,9% NaCl

Placebo + M1006B offset by -10 mmHg; Placebo + M1006B, No offset

Phillips M1006B, offset by -10mmHg DEVICE

Administration of blood pressure module M1006B: offset by -10 mmHg

Iloprost + M1006B offset by -10 mmHg; Placebo + M1006B offset by -10 mmHg

Philips M1006B, No offset DEVICE

Administration of blood pressure module M1006B: No offset

Iloprost + M1006B, No offset; Placebo + M1006B, No offset

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Conscious patients (obeying verbal commands)
• Patients weighing more than 135kg
• In-hospital cardiac arrest (IHCA)
• 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).
• 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).
• Suspected or confirmed acute intracranial bleeding
• Suspected or confirmed acute stroke
• Unwitnessed asystole
• Known limitations in therapy and Do Not Resuscitate-order
• Known disease making 180 days survival unlikely
• Known pre-arrest CPC 3 or 4
• \>4 hours (240 minutes) from ROSC to screening
• Systolic blood pressure \<80 mm Hg in spite of fluid loading/vasopressor and/or inotropic medication/intra-aortic balloon pump/axial flow device\*
• Temperature on admission \<30°C.
• Known allergy to Prostacyclin analogues

Sponsors & Collaborators

• Pär Johansson: lead

Study Sites (1)

Dept. of Cardiology, 2143, Rigshospitalet

Copenhagen, DK-2100, Denmark

Location

Related Publications (3)

• Meyer ASP, Ostrowski SR, Kjaergaard J, Frydland M, Thomsen JH, Johansson PI, Hassager C. Low dose Iloprost effect on platelet aggregation in comatose out-of-hospital cardiac arrest patients: A predefined sub-study of the ENDO-RCA randomized -phase 2- trial. J Crit Care. 2020 Apr;56:197-202. doi: 10.1016/j.jcrc.2019.12.025. Epub 2019 Dec 30.

  PMID: 31945586 DERIVED

• Meyer ASP, Johansson PI, Kjaergaard J, Frydland M, Meyer MAS, Henriksen HH, Thomsen JH, Wiberg SC, Hassager C, Ostrowski SR. "Endothelial Dysfunction in Resuscitated Cardiac Arrest (ENDO-RCA): Safety and efficacy of low-dose Iloprost, a prostacyclin analogue, in addition to standard therapy, as compared to standard therapy alone, in post-cardiac-arrest-syndrome patients.". Am Heart J. 2020 Jan;219:9-20. doi: 10.1016/j.ahj.2019.10.002. Epub 2019 Oct 21.

  PMID: 31710844 DERIVED

• Meyer AS, Ostrowski SR, Kjaergaard J, Johansson PI, Hassager C. Endothelial Dysfunction in Resuscitated Cardiac Arrest (ENDO-RCA): 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 patients: study protocol for a randomized controlled trial. Trials. 2016 Aug 2;17:378. doi: 10.1186/s13063-016-1477-z.

  PMID: 27484224 DERIVED

MeSH Terms

Conditions

Heart Arrest

Interventions

Iloprost; Sodium Chloride

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Prostaglandins, Synthetic; Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Chistian Hassager, MD, DMSc

  Dept. of Cardiology, 2143, Rigshospitalet, Blegdamsvej 0, DK-2100

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, DMSc, MPA

Study Record Dates

• First Submitted: February 4, 2016
• First Posted: February 19, 2016
• Study Start: February 1, 2016
• Primary Completion: August 27, 2016
• Study Completion: February 27, 2017
• Last Updated: March 10, 2021

Record last verified: 2021-03

Locations

DK (1)