The Danish Out-of-Hospital Cardiac Arrest Study
Key facts
- Who runs it
- Christian Hassager
- Where
- Denmark5 sites in 1 countryChoose a country to see its sites
- Status
- Active, not recruiting
- Phase
- Phase 3
- People taking part
- 1,000 people, planned
- Started
- 16 Jun 2023
- Expected to end
- Dec 2027
- Type of study
- Interventional, 8 groupsOne group gets an existing treatment, for comparison.
- Treatments tested
- Dexamethasone
- Backrest elevation
- Early wakeup call
- Olanzapine
- Record updated
- 5 November 2026
Who can take part
- Age
- 18 years and older
- Sex
- Women and men
- Healthy volunteers
- Cannot take part
The registry criteria, word for word
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Who can take part
- 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
Who cannot take part
- Known limitations in therapy and Do Not Resuscitate-order
- Systolic blood pressure <80 mm Hg despite fluid loading/vasopressor and/or inotropic medication (If the systolic blood pressure is recovering during the inclusion window of 180 minutes the patient may be included)
- Ongoing (within 48 h) treatment with olanzapine or dexamethasone
- 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
- Known disease making 180 days survival unlikely
- Known allergy for dexamethasone or olanzapine
- Known back or hip condition that precluded the patients from being positioned with backrest from 0 to 45-degree angle
- Known active fungal disease. Localized skin lesions do not exclude patients from inclusion
- Known or suspected Long QT Syndrome (LQTS)
- Females of childbearing potential if pregnancy is suspected (unless a negative HCG test can rule out pregnancy within the inclusion window)
- Unwitnessed asystole
- Known pre-arrest CPC 3 or 4 functional status
- >3 hours (180 minutes) from ROSC to screening
- Use of intra-aortic balloon pump/axial flow device/ECMO (If the patient is weaned and the device is removed during the inclusion window of 180 minutes the patient may be included)
- Temperature on admission <30°C
- Estimated body weight <45kg
This trial has no sites in United States.
It has sites in one country. Choose a country to see its sites.
About the trial
What the trial wants to find out
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.
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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.
The 8 groups in the trial
- Dexamethasone intervention, activeTreatment being tested
As soon as possible after hospital admittance 20 mg of dexamethasonephosphate (Dexavit, Vital Pharma Nordic ApS, Denmark) will be given intravenously (i.v.) over 15 minutes - followed by 20 mg dexamethasonephosphate (or placebo) i.v. administered daily at 0600 (or at least 8 hours after initial dose) for two days, for a total of 3 doses. For this arm the dexamethasonephosphate solution is provided in the "DANOHCA trial kit" in the form of Dexavit at a concentration of 4mg/mL stored in glass vials of 5mL; three vials are provided in total.
Treatment: Dexamethasone
- Dexamethasone intervention, placeboPlacebo, for comparison
As soon as possible after hospital admittance placebo (isotonic saline) will be given intravenously (i.v.) over 15 minutes - followed by placebo solution administered i.v. daily at 0600 (or at least 8 hours after initial dose) for two days, for a total of 3 doses. For this arm the placebo solution is provided in the "DANOHCA trial kit" in the form of isotonic sodium chloride stored in glass vials of 5mL; three vials are provided in total.
Treatment: Dexamethasone
- Backrest elevation intervention, elevation to 35 degreesTreatment being tested
As soon as possible after hospital admittance the patients will have their headrest positioned at 35 degrees straight elevation of backrest in Semi-Fowler's position (elevated lower limp position). This position will be maintained during the initial 72 hours or until extubated. Adherence to assigned stratum will be checked every 8 hours and cuff pressure will be assessed and corrected if needed at the same time during the intervention period. The backrest position intervention may be temporarily canceled by the treating physician if needed for procedures or mobilization but will return to the assigned position if invasive ventilator treatment with orotracheal intubation is continued. The intervention will be terminated if the patient is extubated, or a tracheostomy is performed, during the intervention period of 72 hours.
Treatment: Backrest elevation
- Backrest elevation intervention, elevation to 5 degreesExisting treatment, for comparison
As soon as possible after hospital admittance the patients will have their headrest positioned at 5 degrees straight elevation of backrest in Semi-Fowler's position. This position will be maintained during the initial 72 hours or until extubated. Adherence to assigned stratum will be checked every 8 hours and cuff pressure will be assessed and corrected if needed at the same time during the intervention period. The backrest position intervention may be temporarily canceled by the treating physician if needed for procedures or mobilization but will return to the assigned position if invasive ventilator treatment with orotracheal intubation is continued. The intervention will be terminated if the patient is extubated, or a tracheostomy is performed, during the intervention period of 72 hours.
Treatment: Backrest elevation
- Early wake-up intervention, wake-up ≤6 hours after ICU admissionTreatment being tested
Patients will be subjected to a wakeup call and potential extubation after ≤6 hours after admission to the ICU. Definition for "ready for extubation" will be: GCS≥12, RASS 0- -1, able to raise arm or voluntary hand shake on command, spontaneous breathing trial and low ventilator settings (pressure support≤14, PEEP≤8 (10 if obese), and FiO2≤40%). A wakeup call may be aborted for the following reasons: seizures, respiratory distress, shock, or "other cause" with specification. Sedation prior to the scheduled wakeup calls is permitted in this early wakeup call group as needed for clinical care, while it is mandatory for the late wakeup call group. For both groups sedation as needed for clinical care will be permitted after the scheduled wakeup calls. For this arm, information on the assigned time for wakeup call is provided in the "DANOHCA trial kit". The assigned time for wakeup will be noted in the electronic patient file.
Treatment: Early wakeup call
- Early wake-up intervention, wake-up 28-36 hours after ICU admissionExisting treatment, for comparison
Patients will be subjected to a wakeup call and potential extubation after 28-36 hours after admission to the ICU. Definition for "ready for extubation" will be: GCS≥12, RASS 0- -1, able to raise arm or voluntary hand shake on command, spontaneous breathing trial and low ventilator settings (pressure support≤14, PEEP≤8 (10 if obese), and FiO2≤40%). A wakeup call may be aborted for the following reasons: seizures, respiratory distress, shock, or "other cause" with specification. Sedation prior to the scheduled wakeup calls is mandatory for this late wakeup call group. For both groups sedation as needed for clinical care will be permitted after the scheduled wakeup calls. For this arm, information on the assigned time for wakeup call is provided in the "DANOHCA trial kit". The assigned time for wakeup will be noted in the electronic patient file.
Treatment: Early wakeup call
- Olanzapine intervention, activeTreatment being tested
As soon as possible after arriving at the ICU olanzapine 10mg (dissolved tablet) is administered by feeding tube. Thereafter 10 mg olanzapine is administered by feeding tube (or orally in awake patients) the following two evenings at 1800 (with a minimum of 12 hours between the initial doses) for a total of 3 doses. Due to the potential QT-prolonging effect, and concern for arrythmia, patients will be excluded prior to randomization if Long QT Syndrome (LQTS) is suspected, and telemetry of heart rhythm is mandatory for 96 hours or until life sustaining therapies are withdrawn. In case of delirium patients are treated according to standard care most often including dexmedetomidine, haloperidol or midazolam. For this arm the olanzapine tablets are provided in the "DANOHCA trial kit" in the form of olanzapin 10mg tablets (Accord Healthcare B.V., The Netherlands); three tablets are provided in total. Prior to administration by feeding tube the tablets are dissolved in water.
Treatment: Olanzapine
- Olanzapine intervention, placeboPlacebo, for comparison
As soon as possible after arriving at the ICU a placebo tablet (dissolved) is administered by feeding tube. Thereafter placebo will be administered by feeding tube (or orally in awake patients) the following two evenings at 1800 (with a minimum of 12 hours between the initial doses) for a total of 3 doses. Due to the potential QT-prolonging effect of olanzapine, and accompanying concern for arrythmia, patients will be excluded prior to randomization if LQTS is suspected, and telemetry of heart rhythm is mandatory for 96 hours or until life sustaining therapies are withdrawn. In case of delirium patients are treated according to standard care most often including dexmedetomidine, haloperidol or midazolam. For this arm the placebo tablets are provided in the "DANOHCA trial kit" in the form of placebo tablets manufactured by the Pharmacy of the Capital Region; three tablets are provided in total. Prior to administration by feeding tube the tablets are dissolved in water.
Treatment: Olanzapine
Data and sources
- Registry record
- Listed on ClinicalTrials.gov and on the EU's official list of trials (CTIS).
- Official title
- The Danish Out-of-Hospital Cardiac Arrest Study - a Randomized, Placebo-controlled, Double-blind, Multi Center Trial
- Publications
- Record updated
- 5 November 2026