The Danish Out-of-Hospital Cardiac Arrest study (DANOHCA)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Rigshospitalet

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

16 Jun 2023 → ongoing

Decision date (initial)

2024-10-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-515997-28-00

EudraCT number

2021-005876-21

ClinicalTrials.gov

NCT05895838

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

The coprimary objectives of the trial for the four interventions:
1. Determine the efficacy of the glucocorticoid "dexamethasone "(Dexamethasone) compared with placebo. The primary endpoint is allcause mortality at 90 days
2. Determine the efficacy of elevated backrest (30-45 degrees) compared with reclined (5-15 degrees) backrest. The primary endpoint is all-cause mortality at 90 days
3. Determine the efficacy of early wake up and extubation ≤6 hours after admission compared with wake up and extubation at 28-36 hours. The primary endpoint is days alive outside hospital within 30 days
4. Determine the efficacy of the antipsychotic drug "olanzapine"(Zyprexa) compared with placebo. The primary endpoint is days alive outside hospital within 30 days

Secondary objectives 6

1. The secondary objectives of the trial are to investigate the effects of the interventions on inhibition of inflammation, cardiac protection, neuroprotection, renal protection, endothelial protection, clinical endpoints including survival and neurological outcome, as well as safety.
2. Advanced hemodynamics study: The Rigshospitalet site (and potential other sites participating in this substudy) will per routine insert a pulmonary artery catheter in the patient. The PAC is part of the routine hemodynamic monitoring in cardiac arrest patients and as such, the patients will not be exposed to excess risk. The study assesses effects of the trial intervention on advanced hemodynamics, in particular the steroid and the backrest position intervention.
3. Retrograde venous catheter and jugular vein blood and micro dialyses Lactate/pyruvate from jugular bulb micro dialysis and blood sampling (headed by Odense University Hospital). Ultrasound guided procedure with minimal risk (bleeding) in experienced centers.
4. Early mobilization of the patients: At the Rigshospitalet site, patients will be allocated to early mobilization (positioning in a chair or more aggressive depending on the patient's condition) after 72 hours and then twice daily by ICU nurses on top of usual care, or usual care (mobilization when awakening and training by physiotherapist once daily) until ICU discharge.
5. CNS evaluation and prognostication: At the Aarhus University Hospital site, the following additional procedures will be performed: 1) Automated pupillometry will be performed three times a day during ICU stay, 2) Sonography of the optic nerve sheath diameter, 3) Transcranial Doppler Sonography will be performed by ultrasound twice a day during ICU stay
6. Coagulation and inflammatory markers: At the Aalborg University Hospital site ROTEM, Multiplate and Calibrated Automated Thrombingeneration (CAT) will be performed 0-24 and 48-72 hours after inclusion (day 1 and 3).

Conditions and MedDRA coding

Patients resuscitated from out-of-hospital cardiac arrest

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Age ≥18 years
2. OHCA of presumed cardiac cause
3. Sustained ROSC. Sustained ROSC is when chest compressions or mechanical circulatory support have been not required for 20 consecutive minutes and signs of circulation persist.
4. Unconsciousness (GCS <9) (patients not able to obey verbal commands) after sustained ROSC at the time of randomization

Exclusion criteria 18

1. Females of childbearing potential (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 (SBP) is recovering during the inclusion window (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 (180 minutes) the patient may be included
12. Temperature on admission <30°C
13. Known allergy from dexamethasone or olanzapine
14. Ongoing (within 48 h) treatment with dexamethasone or olanzapine
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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. The protective effect of dexamethasone decided by all-cause mortality at 90 days following cardiac arrest
2. The protective effect of elevated backrest (30-45 degrees) decided by all-cause mortality at 90 days following cardiac arrest
3. The protective effect of early wake up and extubation ≤6 hours after admission decided by days alive outside hospital within 30 days
4. The protective effect of olanzapine decided by days alive outside hospital within 30 days

Secondary endpoints 13

1. All-cause mortality at 90 days (in study strata where it is not a primary endpoint)
2. Serum Neuron Specific Enolase and Light Chain Neurofilament levels at 48h
3. Markers of organ damage other than CNS: 1) TNT or TNI and CKMB (cardiac) and proBNP during initial 72h and 2) Creatinine during initial 72h and the use of dialysis during the first 30 days post OHCA (renal)
4. Need for vasopressor during ICU stay. (cumulative doses during the first 36 hours and total doses)
5. Mixed blood venous saturation after 12, 24 and 36 hours and the daily during ICU stay
6. Duration of intubation (oral and tracheostomy combined)
7. Number of unconscious patients at 96 hours
8. Number of CAM-ICU positive patients 24 hours after extubation
9. Number of CAM-ICU negative days
10. Number of days without pharmacological treatment for delirium (other than study drug during the intervention period)
11. ICU length of stay
12. Hospital length of stay (including in-patient rehabilitation and transfer to referral hospital)
13. CPC and mRS at ICU discharge, at hospital discharge and at 90 days

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Rigshospitalet

Sponsor organisation

Rigshospitalet

Address

Blegdamsvej 9

City

Copenhagen Oe

Postcode

2100

Country

Denmark

Scientific contact point

Organisation

Rigshospitalet

Contact name

Christian Hingstrup Hassager

Public contact point

Organisation

Rigshospitalet

Contact name

Christian Hingstrup Hassager

Third parties 4

Locations

1 EU/EEA country · 5 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 18 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications