Clinical trial • Phase I | Phase II • Neurology

SODIUM CHLORIDE for Coma (disorders of consciousness) due to acute traumatic and non-traumatic brain injury

Phase I | Phase II trial of SODIUM CHLORIDE for Coma (disorders of consciousness) due to acute traumatic and non-traumatic brain injury.

Overview

Trial Therapeutic Area: Neurology
Trial Disease: Coma (disorders of consciousness) due to acute traumatic and non-traumatic brain injury
Trial Stage: Phase I | Phase II
Drug Modality: Small molecule

Key dates

Initial CTIS Submission Date: 05-12-2023
First CTIS Authorization Date: 28-05-2024

Trial design

Randomised, three-arm allocation 1:1:1: test arms: apomorfin pharmswed 5 mg/ml solution for infusion (apomorphine hydrochloride hemihydrate; route: subcutaneous; product max daily/total dose reported as 2 mg), pex010 psilocybin capsules (25 mg psilocybin; route: oral; product max daily/total dose reported as 25 mg). comparator/placebo: natriumklorid fresenius kabi 9 mg/ml solution for infusion (sodium chloride iv) listed as placebo. specific schedules not detailed in ctis record.-controlled, adaptive Phase I | Phase II trial in Denmark.

Randomised: Yes
Comparator: Three-arm allocation 1:1:1: Test arms: Apomorfin PharmSwed 5 mg/ml solution for infusion (apomorphine hydrochloride hemihydrate; route: subcutaneous; product max daily/total dose reported as 2 mg), PEX010 Psilocybin Capsules (25 mg psilocybin; route: oral; product max daily/total dose reported as 25 mg). Comparator/placebo: Natriumklorid Fresenius Kabi 9 mg/ml solution for infusion (sodium chloride IV) listed as Placebo. Specific schedules not detailed in CTIS record.
Adaptive: True, embedded dose-escalation dose-finding element described: an initial embedded dose-finding Phase 1 study of n=12 patients with cohorts of 4 patients at 1 mg, 4 patients at 10 mg, and 4 patients at 25 mg (dose escalation for safety), followed by the randomized regional trial. No additional formal interim analysis or stopping rules specified in the CTIS summary.
Single Multiple Or Escalation Dose Combined: Yes
Target Sample Size: 396
Trial Duration For Participant: 90

Eligibility

Recruits 396 Vulnerable population selected: clinically unresponsive (coma) adult ICU patients. Study excludes patients without next-of-kin consent, and subject information / informed consent and substitute consent forms are included in the application (documents: 'Stedfortrdende Samtykke', multiple subject information and consent documents). Consent is therefore expected to be obtained from next-of-kin / substitute decision-makers due to patient incapacity..

Pregnancy Exclusion: Pregnancy
Vulnerable Population: Vulnerable population selected: clinically unresponsive (coma) adult ICU patients. Study excludes patients without next-of-kin consent, and subject information / informed consent and substitute consent forms are included in the application (documents: 'Stedfortrdende Samtykke', multiple subject information and consent documents). Consent is therefore expected to be obtained from next-of-kin / substitute decision-makers due to patient incapacity.

Inclusion criteria

{"criterion_text":"- 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"}
{"criterion_text":"- Unconsciousness is expected by the attending physicians to last for ≥3 days"}
{"criterion_text":"- Age ≥18 years"}

Exclusion criteria

{"criterion_text":"- Continuous pharmacologically sedation"}
{"criterion_text":"- Expected survival <7 days"}
{"criterion_text":"- Lack of Danish or English language proficiency"}
{"criterion_text":"- Lack of next-of-kin consent"}
{"criterion_text":"- Residency outside of Denmark"}
{"criterion_text":"- Pregnancy"}

Endpoints

Primary endpoints

{"endpoint_text":"- Time to awakening within 30 days (overall safety)","definition_or_measurement_approach":"Time from randomisation/intervention to awakening within 30 days; endpoint phrased as 'Time to awakening within 30 days (overall safety)'. No additional measurement detail provided in the CTIS data."}

Secondary endpoints

{"endpoint_text":"- Pupillary function (pupillometry, including spontaneous pupillary function and during a mental arithmetic paradigm)","definition_or_measurement_approach":"Pupillometry measurements of spontaneous pupillary function and during a mental arithmetic paradigm (no further measurement definition provided)."}
{"endpoint_text":"- Neurovascular coupling (NIRS-EEG, including spontaneous cortical activity and activation during a tongue motor imagery paradigm) at days 1 and 7","definition_or_measurement_approach":"NIRS-EEG assessment of neurovascular coupling including spontaneous cortical activity and activation during a tongue motor imagery paradigm at days 1 and 7."}
{"endpoint_text":"- Clinical outcome at day 90 (GOS-E)","definition_or_measurement_approach":"Glasgow Outcome Scale - Extended (GOS-E) assessed at day 90."}
{"endpoint_text":"- Days alive outside the ICU","definition_or_measurement_approach":"Count of days a participant is alive and not in ICU (no further details provided)."}
{"endpoint_text":"- Serious adverse reactions (SARs), somatic and neuropsychiatric","definition_or_measurement_approach":"Recording and classification of serious adverse reactions (somatic and neuropsychiatric); no further definition provided."}
{"endpoint_text":"- Serious adverse events, somatic and neuropsychiatric","definition_or_measurement_approach":"Recording and classification of serious adverse events (somatic and neuropsychiatric); no further definition provided."}

Recruitment

Planned Sample Size: 396
Recruitment Window Months: 60
Consent Approach: Because participants are clinically unresponsive, consent is obtained from next-of-kin / substitute decision-makers; lack of next-of-kin consent is an exclusion criterion. Subject information and informed consent documents and a substitute consent form ('Stedfortrdende Samtykke') are included in the application. Languages indicated by exclusion (lack of Danish or English proficiency) imply consent materials in Danish and English.

Methods

In-hospital recruitment of clinically unresponsive adult patients admitted to participating ICUs in Denmark (sites listed are hospital ICU/departments); recruitment procedures and consent documents provided ('informedconsent_patientrecruitmentprocedure' document). Target population: adult ICU patients with coma expected to last ≥3 days.

Geography

Total Number Of Sites: 3
Total Number Of Participants: 384

Denmark

Earliest CTIS Part Ii Submission Date: 21-05-2024
Latest Decision Or Authorization Date: 27-02-2025
Processing Time Days: 282
Number Of Sites: 3
Number Of Participants: 384

Sites

Site Name: Rigshospitalet (Nordre Ringvej 57, Glostrup)
Department Name: Dept. of Neuroanaestelogy, Rigshospitalet-Glostrup, Copenhagen University Hospital
Principal Investigator Name: Margit Smitt
Principal Investigator Email: margit.smitt.01@regionh.dk
Contact Person Name: Margit Smitt
Contact Person Email: margit.smitt.01@regionh.dk

Site Name: Rigshospitalet (Blegdamsvej 9, Copenhagen Oe)
Department Name: Dept. of Neurology (sect 7076), Rigshospitalet-Blegdamsvej, Copenhagen University Hospital
Principal Investigator Name: Daniel Kondziella
Principal Investigator Email: daniel.kondziella@regionh.dk
Contact Person Name: Daniel Kondziella
Contact Person Email: daniel.kondziella@regionh.dk

Site Name: Bispebjerg Hospital (Bispebjerg Bakke 23, Copenhagen Nv)
Department Name: Dept. of Anaesthesia and Intensive Care, Bispebjerg Hospital, Copenhagen University Hospital
Principal Investigator Name: Christian Sylvest Meyhoff
Principal Investigator Email: christian.sylvest.meyhoff@regionh.dk
Contact Person Name: Christian Sylvest Meyhoff
Contact Person Email: christian.sylvest.meyhoff@regionh.dk

Sponsor

Primary sponsor

Full Name: Rigshospitalet
Organisation Type: Hospital/Clinic/Other health care facility
Country Of Registered Address: Denmark

Third parties

{"country":"Denmark","full_name":"Frederiksberg Hospital","duties_or_roles":"1","organisation_type":"Hospital/Clinic/Other health care facility"}

Investigational products

Investigational Product Name: Natriumklorid Fresenius Kabi 9 mg/ml infusjonsvæske, oppløsning
Active Substance: SODIUM CHLORIDE
Modality: Small molecule
Routes Of Administration: INTRAVENOUS
Route: INTRAVENOUS
Authorisation Status: Authorised (marketing/MA data present in CTIS record)
Maximum Dose: maxDailyDoseAmount 10 (units per product record)

Investigational Product Name: Apomorfin PharmSwed 5 mg/ml infusjonsvæske, oppløsning
Active Substance: APOMORPHINE HYDROCHLORIDE HEMIHYDRATE
Modality: Small molecule
Routes Of Administration: SUBCUTANEOUS
Route: SUBCUTANEOUS
Authorisation Status: Authorised (marketing/MA data present in CTIS record)
Maximum Dose: maxDailyDoseAmount 2 (units per product record)

Investigational Product Name: PEX010 Psilocybin Capsules ( 25mg psilocybin)
Active Substance: DRY EXTRACT FROM PSILOCYBE CUBENSIS (15-25:1), EXTRACTION SOLVENT: METHANOL (psilocybin-containing extract)
Modality: Small molecule
Routes Of Administration: ORAL
Route: ORAL
Authorisation Status: Investigational / locally supplied (product record prodAuthStatus=1; MIA number present)
Starting Dose: 1 mg (dose-finder cohort start)
Dose Levels: 1 mg, 10 mg, 25 mg (dose-finder cohorts as stated in trial justification)
Maximum Dose: maxDailyDoseAmount 25 (units per product record)
Dose Escalation Increase: Initial 1 mg, then 10 mg, then 25 mg

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