Overview
Sponsor-declared trial summary
Phase
Human pharmacology (Phase I) - Other
Status
Ongoing, recruiting
Participants planned
384
Countries
1
Sites
3
Coma and other disorders of consciousness due to acute traumatic and non-traumatic brain injury
To do a dose escalation study to establish the safety of utilizing apomorphine and psilocybin in unresponsive ICU pa-tients with acute brain injury.
Key facts
- Sponsor
- Rigshospitalet
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Nervous System Diseases [C10]
- Trial duration
- 26 Feb 2025 → ongoing
- Decision date (initial)
- 2024-05-28
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Safety
To do a dose escalation study to establish the safety of utilizing apomorphine and psilocybin in unresponsive ICU pa-tients with acute brain injury.
Secondary objectives 1
- To investigate for somatic and neuropsychiatric adverse events
Conditions and MedDRA coding
Coma and other disorders of consciousness due to acute traumatic and non-traumatic brain injury
Regulatory references
- Plan to share IPD
- No
- IPD plan description
- N/A
| EU CT number | Title | Sponsor |
|---|---|---|
| 2023-503617-30-00 | Boosting recovery through excitation of arousal and awareness in comatose patients: The BREA2KTHROUGH trial | Rigshospitalet |
| 2023-503617-30-01 | Boosting recovery through excitation of arousal and awareness in comatose patients: The BREA2KTHROUGH trial | Rigshospitalet |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Clinically unresponsive patients admitted to the ICU either with a traumatic or non-traumatic brain injury or a systemic medical or surgical condition causing non-medically induced coma
- Unconsciousness is expected by the attending physicians to last for ≥3 days
- Age ≥18 years
Exclusion criteria 6
- Continuous pharmacologically sedation
- Expected survival <7 days
- Lack of Danish or English language proficiency
- Lack of next-of-kin consent
- Residency outside of Denmark
- Pregnancy
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Time to awakening within 30 days (overall safety)
Secondary endpoints 6
- Pupillary function (pupillometry, including spontaneous pupillary function and during a mental arithmetic paradigm)
- Neurovascular coupling (NIRS-EEG, including spontaneous cortical activity and activation during a tongue motor imagery paradigm) at days 1 and 7
- Clinical outcome at day 90 (GOS-E)
- Days alive outside the ICU
- Serious adverse reactions (SARs), somatic and neuropsychiatric
- Serious adverse events, somatic and neuropsychiatric
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
PEX010 Psilocybin Capsules ( 25mg psilocybin)
PRD10405999 · Product
- Active substance
- Dry Extract From Psilocybe Cubensis (15-25:1), Extraction Solvent: Methanol
- Pharmaceutical form
- CAPSULES
- Route of administration
- ORAL
- Max daily dose
- 25 mg milligram(s)
- Max total dose
- 25 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Not Authorised
- MA holder
- RIGSHOSPITALET
- Paediatric formulation
- No
- Orphan designation
- No
Apomorfin PharmSwed 5 mg/ml infusjonsvæske, oppløsning
PRD8079974 · Product
- Active substance
- Apomorphine Hydrochloride Hemihydrate
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 2 mg milligram(s)
- Max total dose
- 2 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- N04BC07 — APOMORPHINE
- Marketing authorisation
- 12-9111
- MA holder
- EVOLAN PHARMA AB
- MA country
- Norway
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Placebo 1
Natriumklorid Fresenius Kabi 9 mg/ml infusjonsvæske, oppløsning
PRD2128245 · Product
- Active substance
- Sodium Chloride
- Substance synonyms
- SODIUM CHLORID, SODIUM CHLORIDE (FOR PH ADJUSTMENT)
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 10 mg/g milligram(s)/gram
- Max total dose
- 2 mg milligram(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Authorised
- ATC code
- B05BB01 — ELECTROLYTES
- Marketing authorisation
- 5846
- MA holder
- FRESENIUS KABI NORGE AS
- MA country
- Norway
- 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
- Daniel Kondziella
Public contact point
- Organisation
- Rigshospitalet
- Contact name
- Daniel Kondziella
Third parties 1
| Organisation | City, country | Duties |
|---|---|---|
| Frederiksberg Hospital ORG-100028217
|
Frederiksberg, Denmark | On site monitoring |
Locations
1 EU/EEA country · 3 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Denmark | Ongoing, recruiting | 384 | 3 |
| Rest of world | — | 0 | — |
Investigational sites
Bispebjerg Hospital
Dept. of Anaesthesia and Intensive Care, Bispebjerg Hospital, Copenhagen University Hospital, Bispebjerg Bakke 23, 2400, Copenhagen Nv
Rigshospitalet
Dept. of Neuroanaestelogy, Rigshospitalet-Glostrup, Copenhagen University Hospital, Nordre Ringvej 57, 2600, Glostrup
Rigshospitalet
Dept. of Neurology (sect 7076), Rigshospitalet-Blegdamsvej, Copenhagen University Hospital, 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 | 2025-02-26 | 2025-02-26 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 13 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | Protocol BREA2KTHROUGH | 1.4.2 |
| Protocol (for publication) | Protocol BREA2KTHROUGH_track changes | 1.4.2 |
| Recruitment arrangements (for publication) | informedconsent_patientrecruitmentprocedure | 1.1 |
| Subject information and informed consent form (for publication) | Deltagerinformation Paarrende | 1.2 |
| Subject information and informed consent form (for publication) | Deltagerinformation Paarrende_track changes | 1.2 |
| Subject information and informed consent form (for publication) | Deltagerinformation Patient | 1.2 |
| Subject information and informed consent form (for publication) | Deltagerinformation Patient_track changes | 1.2 |
| Subject information and informed consent form (for publication) | Dine rettigheder som forsgsperson i forsg med medicin | 1 |
| Subject information and informed consent form (for publication) | Samtykkeerklring Patient | 1.1 |
| Subject information and informed consent form (for publication) | Stedfortrdende Samtykke | 1.1 |
| Summary of Product Characteristics (SmPC) (for publication) | Placeholder document | 1 |
| Synopsis of the protocol (for publication) | BREA2KTHROUGH DOSEFINDER_one pager | 1 |
| Synopsis of the protocol (for publication) | Protocol synopsis Danish | 1 |
Application history
6 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2023-12-05 | Denmark | Acceptable 2024-03-11
|
2024-05-28 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-07-12 | Denmark | Acceptable 2024-07-31
|
2024-07-31 |
| 3 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-12-04 | Denmark | Acceptable 2024-07-31
|
2024-12-04 |
| 4 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-12-10 | Denmark | Acceptable 2024-12-18
|
2024-12-18 |
| 5 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-01-23 | Denmark | Acceptable 2025-02-27
|
2025-02-27 |
| 6 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-04-12 |