The Danish Out-of-Hospital Cardiac Arrest Study - a Randomized, Placebo-controlled, Double-blind, Multi Center Trial

H-21077461

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.

2023-06-16

2027-09-01

2027-12-01

Recruiting

Early phase I

1000

Inclusion Criteria: 1. Age ≥18 years 2. OHCA of presumed cardiac cause 3. Sustained ROSC, defined as persistent signs of circulation and no need for chest compressions or mechanical circulatory support for 20 minutes 4. Unconsciousness (GCS \<9) (patients not able to obey verbal commands) after sustained ROSC at the time of randomization Exclusion Criteria: 1. Females of childbearing potential if pregnancy is suspected (unless a negative HCG test can rule out pregnancy within the inclusion window) 2. Known bleeding diathesis (medically induced coagulopathy (e.g. warfarin, NOAC, clopidogrel) does not exclude the patient) 3. Suspected or confirmed acute intracranial bleeding 4. Suspected or confirmed acute stroke 5. Unwitnessed asystole 6. Known limitations in therapy and Do Not Resuscitate-order 7. Known disease making 180 days survival unlikely 8. Known pre-arrest CPC 3 or 4 functional status 9. \>3 hours (180 minutes) from ROSC to screening 10. 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) 11. 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) 12. Temperature on admission \<30°C 13. Known allergy for dexamethasone or olanzapine 14. Ongoing (within 48 h) treatment with olanzapine or dexamethasone 15. Known back or hip condition that precluded the patients from being positioned with backrest from 0 to 45-degree angle 16. Known or suspected Long QT Syndrome (LQTS) 17. Known active fungal disease. Localized skin lesions do not exclude patients from inclusion 18. Estimated body weight \<45kg

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2023-09-21