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The Danish Out-of-Hospital Cardiac Arrest Study

ConditionsOut-Of-Hospital Cardiac ArrestPost-Cardiac Arrest Syndrome
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorChristian Hassager

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age ≥18 years

OHCA of presumed cardiac cause

Sustained ROSC, defined as persistent signs of circulation and no need for chest compressions or mechanical circulatory support for 20 minutes

Unconsciousness (GCS <9) (patients not able to obey verbal commands) after sustained ROSC at the time of randomization

Disqualifiers

Females of childbearing potential if pregnancy is suspected (unless a negative HCG test can rule out pregnancy within the inclusion window)

Known bleeding diathesis (medically induced coagulopathy (e.g. warfarin, NOAC, clopidogrel) does not exclude the patient)

Suspected or confirmed acute intracranial bleeding

Suspected or confirmed acute stroke

Trial design

Design model

Factorial

Treatments tested in this trial

  • Dexamethasone

    Drug

    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.

  • Backrest elevation

    Procedure/Surgery

    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).

  • Early wakeup call

    Procedure/Surgery

    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.

  • Olanzapine

    Drug

    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.

Treatment groups

1,000 Participants
are divided into 8 treatment groups

8

Treatment groups

See each treatment group below.

Group A: Dexamethasone intervention, activeExperimental treatment 1 intervention
Group B: Dexamethasone intervention, placeboPlacebo comparator 1 intervention
Group C: Backrest elevation intervention, elevation to 35 degreesExperimental treatment 1 intervention
Group D: Backrest elevation intervention, elevation to 5 degreesActive comparator 1 intervention
Group E: Early wake-up intervention, wake-up ≤6 hours after ICU admissionExperimental treatment 1 intervention
Group F: Early wake-up intervention, wake-up 28-36 hours after ICU admissionActive comparator 1 intervention
Group G: Olanzapine intervention, activeExperimental treatment 1 intervention
Group H: Olanzapine intervention, placeboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Steroid intervention primary endpoint: All-cause mortality

Number of patients dying from all causes

Time frame
90 days
2

Back rest position intervention primary endpoint: All-cause mortality

Number of patients dying from all causes

Time frame
90 days
3

Early wakeup and extubation intervention primary endpoint: Days alive outside hospital

Counted as days alive outside of hospital after discharge

Time frame
30 days
4

Olanzapine intervention primary endpoint: Days alive outside hospital

Counted as days alive outside of hospital after discharge

Time frame
30 days

Secondary outcomes

1

Number of patients dying from all causes

Applies to the Early wakeup and extubation intervention, as well as Olanzapine intervention

Time frame
90 days
2

Neuron Specific Enolase and Neurofilament Light Chain levels

Serum markers for brain injury; Differences in levels between intervention groups assessed at 48 hours; Applies to all interventions

Time frame
48 hours
3

Troponin I, Troponin T, and Creatine Kinase Myocardial Band

Plasma markers of myocardial injury; Differences in levels between intervention groups assessed during initial 72 hours; Applies to all interventions

Time frame
0-72 hours
4

Plasma Creatinine and use of dialysis

Markers of kidney injury; Creatinine will be assessed during initial 72 hours, and use of dialysis will be assessed during initial 30 days

Time frame
Creatinine: initial 72 hours; Dialysis: initial 30 days

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Christian Hassager

Lead sponsor

Rigshospitalet, Denmark

Sponsor institution

Source ClinicalTrials.gov
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