The Danish Out-of-Hospital Cardiac Arrest Study

Summary

After resuscitation from Out-of-Hospital Cardiac Arrest (OHCA) patients experience Post Cardiac Arrest Syndrome due to ischemia and reperfusion injury. It consists of systemic inflammation, cerebral and myocardial dysfunction, and the condition that led to the arrest. Most OHCA patients will receive critical care intubated in an Intensive Care Unit (ICU). Despite this \~50% die; mainly due to brain injury. Several targets can be considered for improving outcomes. To dampen systemic inflammation and optimize cerebral perfusion seem important. Deep sedation has been required for targeted temperature management (TTM) but may also be brain protective. After end of sedation, many patients have some cerebral dysfunction that may facilitate delirium.

The aim of this trial is therefore to improve treatment of comatose OHCA patients by evaluating 4 interventions in a factorial design addressing each of these targets in a randomized clinical trial:

1. Systemic inflammation: Anti-inflammatory treatment with high dose steroids (dexamethasone) or placebo.
2. Cerebral perfusion: Backrest elevation during sedation at 5 or 35 degrees.
3. Duration of sedation: Early wakeup call and potential extubation at ≤6 hours after admission or later as current standard practice at 28-36 hours.
4. Delirium: Prophylactic treatment with anti-psychotic medication (olanzapine) or placebo.

The trial is designed as a phase III trial, randomizing 1000 patients at Danish cardiac arrest centers.

The primary endpoint is 90 days all-cause mortality for the interventions targeting systemic inflammation and cerebral perfusion, while it is days alive outside of hospital within 30 days for the interventions concerning duration of sedation and delirium.

The trial has potential to improve outcomes for comatose OHCA patients - a group with a grave prognosis with currently only limited evidence-based treatments.

Conditions

• Out-Of-Hospital Cardiac Arrest
• Post-Cardiac Arrest Syndrome

Interventions

DRUG

Dexamethasone

Patients will be allocated to intravenous administration of dexamethasonephosphate 20mg (Dexavit, Vital Pharma Nordic ApS, Denmark) or placebo at admission and again the following two mornings until discharge from ICU or a maximum of 3 doses.

PROCEDURE

Backrest elevation

Patients will be allocated to have their headrest positioned at 35 degrees backrest vs 5 degrees straight elevation of backrest for 72 hours (or until extubation if occuring prior to 72 hours).

PROCEDURE

Early wakeup call

Patients will be allocated to early wakeup call and potential extubation after ≤6 hours or late wakeup call and extubation between 28-36 hours after admission to the ICU.

DRUG

Olanzapine

Patients will be allocated to olanzapine 10 mg (Olanzapin, Accord Healthcare B.V., The Netherlands) administered by feeding tube (or orally in awake patients) or matching placebo at admission and again the following two evenings until discharge from ICU or a maximum of 3 doses.

Sponsors & Collaborators

• Christian Hassager

  lead OTHER

Principal Investigators

• Christian Hassager, MD DMSc · Dept. of Cardiology, Rigshospitalet

• Jesper Kjaergaard, MD PhD DMSc · Dept. of Cardiology, Rigshospitalet

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

FACTORIAL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-06-16

Primary Completion

2027-09-30

Completion

2027-12-31

Countries

• Denmark

Study Locations