Steroid Treatment After Resuscitated Out-of-Hospital Cardiac Arrest

NCT04624776 | Completed Phase 2 DMC

• 1 other identifier: EudraCT: 2020-000855-11
• Study Type: interventional
• Target: 158
• Locations: 1 country
• Sites: 2

Brief Summary

Comatose patients resuscitated from Out-of-Hospital Cardiac Arrest (OHCA) often develop a complicated systemic inflammatory response and have a poor prognosis with neurological damage being the most common cause of death. This study will investigate the anti-inflammatory and neuroprotective effect of early treatment with the glucocorticoid methylprednisolone measured by interleukin-6 and neuron-specific enolase levels in resuscitated comatose OHCA-patients.

Conditions

Out-Of-Hospital Cardiac Arrest; Cardiac Arrest; Cardiac Arrest With Successful Resuscitation; Post Cardiac Arrest Syndrome; Systemic Inflammatory Response Syndrome; Neurological Injury

Keywords

OHCA; PCAS; Inflammation; Neuroprotection; Methylprednisolone; Solu-Medrol

Outcome Measures

Primary Outcomes (2)

• Concentration of IL-6

  Interleukin 6 (ng/L)

  Daily measurements from admission to 72 hours after admission

• Concentration of NSE

  Neuron-specific-enolase (ng/L)

  Daily measurements from admission to 72 hours after admission

Secondary Outcomes (13)

• Markers of inflammation, biomarkers

  Daily measurements the first three days following admission

• Markers of inflammation, cell count

  Daily measurements the first three days following admission

• Markers of kidney and hepatic injury

  Daily measurements the first three days following admission

• Marker of the coagulation system, biomarker

  Plasma fibrinogen the first three days from admission

• Marker of the coagulation system, functional analysis

  Thromboelastography at admission and at 48 hours

Study Arms (2)

Methylprednisolone

ACTIVE COMPARATOR

A five minutes bolus infusion of 250 mg (4 mL) methylprednisolone to inhibit inflammatory and neurological damage following resuscitated out-of-hospital cardiac arrest. The infusion of methylprednisolone will be given following five minutes of sustainable ROSC in the prehospital setting.

Drug: Methylprednisolone

Isotonic saline

PLACEBO COMPARATOR

A bolus infusion of 4 mL isotonic saline (NaCl 0.9%).

Drug: Isotonic saline

Interventions

Methylprednisolone DRUG

A dosis of 250 mg methylprednisolone is suspended in isotonic saline to a total volume of 4 mL prior to infusion.

Also known as: Solu-Medrol

Methylprednisolone

Isotonic saline DRUG

A bolus infusion of 4 mL isotonic saline (NaCl 0.9%).

Also known as: Placebo

Isotonic saline

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
• Unconsciousness (GCS ≤8) upon pre-hospital randomization
• Sustained ROSC for at least 5 minutes
• Randomization and start of study medicine infusion within 30 minutes of sustained ROSC.

You may not qualify if:

• Asystole as primary ECG rhythm
• Women of childbearing capacity
• Known therapy limitation
• Known allergy to methylprednisolone
• Known pre-arrest modified Rankin Scale (mRS) score of 4-5
• Temperature upon randomization \<30° C
• \>30 minutes to sustained ROSC.

Sponsors & Collaborators

• Christian Hassager: lead

Study Sites (2)

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Gentofte Hospital

Gentofte Municipality, 2820, Denmark

Location

Related Publications (36)

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• Obling LER, Beske RP, Wiberg S, Folke F, Moeller JE, Kjaergaard J, Hassager C. Steroid treatment as anti-inflammatory and neuroprotective agent following out-of-hospital cardiac arrest: a randomized clinical trial. Trials. 2022 Nov 22;23(1):952. doi: 10.1186/s13063-022-06838-0.

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MeSH Terms

Conditions

Out-of-Hospital Cardiac Arrest; Heart Arrest; Post-Cardiac Arrest Syndrome; Systemic Inflammatory Response Syndrome; Trauma, Nervous System; Inflammation

Interventions

Methylprednisolone; Methylprednisolone Hemisuccinate; Sodium Chloride

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Reperfusion Injury; Vascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Christian Hassager, MD, DMSc

  Department of Cardiology, The Heart Center, Rigshospitalet, Copenhagen, Denmark

  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: Professor, MD, DMSc, FESC

Model Details: Investigator-initiated, 1:1 randomized, multicenter, double-blind, placebo-controlled clinical trial. A minimum of 120 unconscious OHCA patients will be randomized 1:1 after 5 minutes of sustained ROSC to an infusion of 250 mg (4 mL) methylprednisolone in the pre-hospital setting. The methylprednisolone will be given as a bolus infusion of 1 x 250 mg (1 x 4 mL) over a period of 5 minutes. Patients allocated to placebo will receive 4 mL of isotonic saline (NaCl 0.9%).

Study Record Dates

• First Submitted: October 12, 2020
• First Posted: November 12, 2020
• Study Start: October 10, 2020
• Primary Completion: July 15, 2022
• Study Completion: February 28, 2023
• Last Updated: March 29, 2023

Record last verified: 2023-03

Locations

DK (2)