Overview
Sponsor-declared trial summary
Phase
Phase III and Phase IV (Integrated)
Status
Ongoing, recruiting
Participants planned
282
Countries
1
Sites
2
Out-of-hospital cardiac arrest
To determine the neuroprotective efficacy of ketamine compared with propofol administered as part of sedation for intubation after initial resuscitation from OHCA.
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
- 11 Dec 2024 → ongoing
- Decision date (initial)
- 2024-10-01
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- Yes
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety, Therapy, Prophylaxis
To determine the neuroprotective efficacy of ketamine compared with propofol administered as part of sedation for intubation after initial resuscitation from OHCA.
Secondary objectives 1
- To determine the effects of ketamine compared with propofol on survival and neurological outcomes at discharge and after 180 days post-cardiac arrest in patients resuscitated from OHCA.
Conditions and MedDRA coding
Out-of-hospital cardiac arrest
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- 1. Age ≥18 years (presumed if not known) 2. OHCA of presumed cardiac cause. * 3. Primary shockable rhythm (ventricular fibrillation or pulseless ventricular tachycardia) ** 4. Decision to perform prehospital intubation after resuscitation (as decided by treating physician) or intubated during CPR with additional need for sedation. 5. Administration of study medicine injection before hospital arrival is considered feasible. 6. ROSC with MAP ≥40 mmHg *i.e. admission to Rigshospitalet or Odense University Hospital: national guidelines state that all OHCA patients with presumed cardiac arrest must be referred to the two main hospitals in the respective regions — Rigshospitalet for all OHCA cases in Region Zealand and the Capital Region, and Odense University Hospital for all OHCA cases in Region South. **If a defibrillator shock by an automated external defibrillator is delivered or advised before arrival of the EMS, it is considered a “primary shockable rhythm.”
Exclusion criteria 1
- 1. Advanced life support TOR exclusion criteria fulfilled 2. Refractory cardiac arrest transferred for extracorporeal membrane oxygenation 3. Woman of childbearing capacity (female aged 18-40, decided by the treating physician if no information is available) 4. Known therapy limitation (known decision made of no resuscitation or intensive therapy) 5. Known allergy to ketamine or propofol 6. Systolic blood pressure >190 mmHg 7. Known chronic disease making 180-day survival unlikely 8. Known pre-arrest mRS score of ≤5 9. Nursing home resident 10. Temperature upon admission <30° C
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Neuron-specific enolase (NSE) measured 48 hours after OHCA
Secondary endpoints 1
- 1. Death from all causes at 180 days after cardiac arrest. 2. CPC- and mRS score at hospital discharge and 180-240 days after cardiac arrest.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
S-ketamin "Pfizer" injektionsvæske, opløsning
PRD422975 · Product
- Active substance
- Esketamine Hydrochloride
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVENOUS BOLUS INJECTION/IV INFUSION
- Max daily dose
- 4 mg/kg milligram(s)/kilogram
- Max total dose
- 4 mg/kg milligram(s)/kilogram
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- N01AX14 — ESKETAMINE
- Marketing authorisation
- 19569
- MA holder
- PFIZER APS
- MA country
- Denmark
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 1
PRD2085381 · Product
- Active substance
- Propofol
- Pharmaceutical form
- EMULSION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS BOLUS INJECTION/IV INFUSION
- Max daily dose
- 6 mg/kg milligram(s)/kilogram
- Max total dose
- 6 mg/kg milligram(s)/kilogram
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- N01AX10 — PROPOFOL
- Marketing authorisation
- 49586
- MA holder
- FRESENIUS KABI AB
- MA country
- Denmark
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
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 Hassager
Public contact point
- Organisation
- Rigshospitalet
- Contact name
- Christian Hassager
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Frederiksberg Hospital ORG-100028217
|
Frederiksberg, Denmark | On site monitoring |
Locations
1 EU/EEA country · 2 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Ongoing, recruiting | 282 | 2 |
| Rest of world | — | 0 | — |
Investigational sites
Odense University Hospital
Department of Cardiothoracic Anesthesiology, J B Winsloews Vej 4, 5000, Odense C
Rigshospitalet
Department of Cardiology, Blegdamsvej 9, 2100, Copenhagen Oe
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Denmark | 2024-12-11 | 2024-12-12 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Serious breaches 1 · Art. 52 CTR
Serious breach SB-119236
- Sponsor became aware
- 2026-01-28
- Date of breach
- 2025-03-29
- Submission date
- 2026-02-13
- Member states concerned
- Denmark
- Categories
- Regulation, Protocol
- Areas impacted
- Regulatory, Data reliability or robustness
- Benefit-risk balance changed
- No
- Description
- Although internal monitoring of adverse events was performed from the beginning of the trial at site OUH, serious adverse events (SAEs) were not systematically classified and recorded in the electronic case report form (eCRF), preventing the sponsor from timely review. Continuous contact between study staff and site personnel within 24 hours after inclusion (as outlined in the protocol) ensured awareness of any events related to the investigational product. No suspected adverse reac-tions (SARs) occurred, and all identified SAEs were unrelated to study medication. The omission delayed sponsor-level docu-mentation and oversight of SAEs but did not affect participant safety or study data validity, as the events were managed and documented locally according to clinical procedures.
- Sponsor actions
- After identifying the documentation deficiency, a dedicated site study personnel member was appointed to ensure systematic classification, entry, and verification of all SAEs in the eCRF. The sponsor verified that retrospective SAE data are now fully entered and aligned with source documentation (completed the 30th of January 2026). Continuous site training and quarterly monitoring visits have been initiated to ensure ongoing compliance with SAE reporting requirements per protocol and regula-tory standards.
| Organisation | City | Country | Type |
|---|---|---|---|
| Odense University Hospital | Odense C | Denmark | Clinical facility BE/BA, Clinical investigator |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 23 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol 2024-515987-29-00_v3_25MAR2025_TC | 1 |
| Protocol (for publication) | D1_Protocol_2024-515987-29-00 | 3.0 |
| Protocol (for publication) | D1_Protocol_2024-515987-29-00_RFI002_track changes | 1.1 |
| Protocol (for publication) | D4_Follow-up_Interview_Protocol | 1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements | 2.1 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_track changes | 2 |
| Recruitment arrangements (for publication) | K1_Recruitment arrangements_v2 1_track changes | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_death_next_of_kin | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_death_next_of_kin_v2_track changes | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_next of kin | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_next of kin_v2 1_track changes | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_next of kinv2_track changes | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_subject | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_subject_v2 1_track changes | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_subjectv2_track changes | 2 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF_trial guardian | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS_ICF_trial guardian_v2 1_track changes | 2.1 |
| Subject information and informed consent form (for publication) | L1_SIS_ICF_trial guardian_v2_track changes | 2 |
| Subject information and informed consent form (for publication) | L2_Other subject information material GDPR | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject information material Information leaflet | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Propolipid_Fresenius Kabi | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC S-ketamine_Phizer | 1 |
| Synopsis of the protocol (for publication) | KETOHCA_trial protocol_v2 1_track changes | 2.1 |
Application history
2 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-07-25 | Denmark | Acceptable 2024-10-01
|
2024-10-01 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2025-03-31 | Denmark | Acceptable 2025-04-15
|
2025-04-15 |