None listed
Conditions
Brief summary
The aim of this research is to confirm the safety and test the effect of EU-C-001 on reducing raised pressure in the brain. Patients with traumatic brain injury (TBI) will receive the best standard of care for their condition, and will also receive one of three different treatment levels of EU-C-001 or a placebo. The hypothesis is that the patients receiving EU-C-001 will have a stronger reduction in the pressure in the brain than patients who receive the placebo treatment.
Interventions
The first fifteen patients will participate in an open-label pilot phase: in addition to the standard of care, patients will receive treatment with four infusions of EU-C-001, each administered as a single intravenous infusion over 15 minutes. The first seven patients will receive EU-C-001 90 mg four times over three days, at time-points 0 hours and 12 hours (Day 1), 36 hours (Day 2) and 60 hours (Day 3). The next four patients will receive EU-C-001 90 mg four times over two days, at time points
The first fifteen patients will participate in an open-label pilot phase: in addition to the standard of care, patients will receive treatment with four infusions of EU-C-001, each administered as a single intravenous infusion over 15 minutes. The first seven patients will receive EU-C-001 90 mg four times over three days, at time-points 0 hours and 12 hours (Day 1), 36 hours (Day 2) and 60 hours (Day 3). The next four patients will receive EU-C-001 90 mg four times over two days, at time points 0 hours and 4 hours (Day 1) and 24 hours and 28 hours (Day 2). The last four patients will receive EU-C-001 four times over two days as a weight-adapted dose (WAD), calculated as 1.58 mg/kg times the patient's body weight in kg. The dosing schedule will remain as with the previous four patients (0 hours, 4 hours, 24 hours and 28 hours). The maximum dose of EU-C-001 to be administered in a single infusion is set at 140 mg. After the open-label pilot phase, subsequent patients will be randomly assigned to one of two treatment arms in a double-blind phase, in addition to the standard of care: Treatment Arm A: treatment consisting of EU-C-001 with weight-adapted dosing (1.58 mg/kg) at time-points 0 hours and 4 hours, on each of four consecutive days, administered as single intravenous infusions over 15 minutes.
Sponsors
Eustralis Pharmaceuticals Ltd, trading as PresSura Neuro
Study design
Allocation
Randomised controlled trial
Intervention model
Other
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
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
Outcome results
None listed