A double-blind placebo-controlled study with an open-label pilot phase, assessing the efficacy, tolerability and safety of EU-C-001 in patients with moderate to severe traumatic brain injury

Phase 2

Recruiting

• Conditions: Traumatic Brain Injury; Neurological - Other neurological disorders; Injuries and Accidents - Other injuries and accidents

• Registration Number: ACTRN12619000074190
• Lead Sponsor: Eustralis Pharmaceuticals Ltd, trading as PresSura Neuro

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2019-01-21
• Last Update Posted: 3 June 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 65

Inclusion Criteria

1. Male or female aged 18 to 70 years at the time the informed consent form is signed by either the patient or the patient’s legally authorized representative
2. Moderate to severe TBI due to blunt mechanism
3. Abnormal computerized tomography (CT) scan consistent with TBI due to blunt mechanism
4. Intracranial pressure monitor in situ, ICP >15 mm Hg at screening in the absence of potential external ICP stimuli, e.g., suctioning, coughing, and turning. The preferred method of ICP measurement is either intraventricular, intraparenchymal, or subdural, where possible
5. The GCS score at Screening is the most recent GCS score assessed at the hospital after resuscitation. If this is not available, the GCS score assessed by the ambulance personnel/paramedics prior to arrival at hospital will be used.
a. If the Total Score is assessable (range 3 to 15), a patient is eligible for inclusion if their score is in the range 3 to 12
b. If only the Eye and Motor scores are assessable (range 2 to 10), a patient is eligible for inclusion if their score is in the range 2 to 8
c. If only the Motor score is assessable (range 1 to 6), a patient is eligible for inclusion if their score is in the range 1 to 5
6. Onset of TBI within the last 72 hours

Exclusion Criteria

1. Documented continuously elevated ICP >20 mm Hg for >12 hours after elevated ICP was first measured/observed
2. Use of an extraventricular drain for ICP control
3. Injury deemed non-survivable by study team
4. Penetrating brain injury
5. Bilateral dilated, unresponsive pupils
6. Imminent cranial or extracranial surgery
7. Patients in whom a subdural and/or extradural haematoma are present and are considered by the investigator to be the predominant cause of raised ICP
8. Concomitant use of thiopentone
9. Cervical spinal cord injury
10. Cardiopulmonary resuscitation performed by medical personnel/paramedics
11. Life-threatening systemic injuries, additional injuries, or conditions requiring medical treatment which would confound the assessment of the effects and/or safety of study medication
12. Morbid obesity with body mass index =40 kg/m2
13. Severe or unstable pre-existing respiratory and hemodynamic conditions
14. Hypoxemia (oxygen saturation <80%, measured by pulse oximetry)
15. Hypotension (sustained systolic blood pressure <70 mm Hg despite adequate volume resuscitation and vasopressors)
16. Status epilepticus
17. Pregnancy
18. Clinically significant anemia (hemoglobin <7 g/dL)
19. History of blood clotting disorder; exclude if international normalized ratio (INR) >1.5 and/or thrombocytes <50,000/µL
20. Moderate to severe renal impairment with estimated glomerular filtration rate <60 mL/min
21. Hepatic dysfunction with total bilirubin >2 × upper limit of normal and INR >1.5
22. Any major neurological or psychiatric disorder associated with significant impairment of cognitive function or motor function, e.g., Alzheimer’s disease with dementia, Parkinson’s disease, Huntington’s disease, alcohol or substance abuse
23. Participating in or has participated in other investigational interventional studies (drug or device) within the last 30 days (or 5 times the half-life of the previously administered investigational compound, whichever is longer) prior to study treatment initiation, with the exception of studies assessing approved medicinal products. Exception is made for co-enrolment in the PATCH study of tranexamic acid, allowing inclusion if treatment with EU-C-001 is initiated not earlier than 7 half-lives (14 hours) after the end of the last administration of study drug from the PATCH study.
24. Wearing an opt out bracelet or is known not to wish to participate in this type of study

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Double-blind phase: AUEC(0-96h) for Therapy Intensity Level (TIL), measured every 4 hours after the start of infusion of study medication - Comparison between active and placebo groups for AUEC(0-96h) for TIL[ 96 h after start of first infusion.];Open-label pilot phase: To assess the safety of EU-C-001 in the target population of the highest dose to be tested in the double-blind phase, based on adverse events, such as local tolerability, intravascular hemolysis, or central nervous system effects.[ Day 5 after start of first dose]