Comatose patients with traumatic brain injury (TBI).
Conditions
Interventions
Product Name: KN 38-7271 SOL 0.0001% 250 mL 102 INF
Product Code: KN 38-7271
Pharmaceutical Form: Intravenous infusion
CAS Number: 212188-60-8
Current Sponsor code: KN 38-7271
Other descriptive name:
Sponsors
KeyNeurotek Pharmaceuticals AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age 18-65 years; 2. Comatose patients with severe TBI and a Glasgow Coma Score (GCS) 3-8 as initially assessed (eg, by the emergency physician) after resuscitation and hemodynamical stabilization but before intubation and/or sedation; On arriving the hospital, the study physician should use his own judgment based on the report of the emergency doctor and the current status of the patient that the coma is due to trauma. Patients who have a GCS>8 and/or are not comatose and/or are not comatose at the scene where the trauma occurred but deteriorate, eg, during transport to the hospital, may still be eligible for the study; 3. Blunt severe head trauma; 4. Hemodynamically stable (systolic blood pressure > 90 mmHg) after resuscitation/stabilization; 5. Start of treatment with study medication is feasible within 4.5 hours of onset of TBI (where onset of TBI is the time of impact. If the exact time of impact is not known, a conservative approach will be followed for the estimation of time of impact, ie, if an interval was provided for time of impact—eg, between 10:00 and 11:00 hours—the earlier end of that interval [10:00 hours] should be assumed as time of impact; 6. Informed consent obtained according to national and local legislation (see Section 9.7); 7. Negative urine pregnancy test in all female patients (as all patients are comatose and child bearing potential may not be ruled out in some women). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. TBI due to penetrating head injuries or gun shot wounds; 2. Any major spinal cord injury; 3. Initially bilateral non-reactive dilated pupils; 4. Major injury that requires/is expected to require >2500 mL of blood (> 5 blood units) within 12 hours of TBI; Note: Patients requiring decompressive surgery may still be eligible for this study; 5. Known or CT scan evidence of previous major cerebral damage; 6. Coma due to other causes than TBI; If information on the following exclusion criteria is available prior to randomization, these patients should be excluded, see Section 4.3. 7. Receiving an experimental drug within 4 weeks prior to current injury; 8. Known history of disability that may interfere with further evaluation; 9. Any severe concomitant disease that may either relevantly affect the safety of the patient, the efficacy of the drug (eg, psychiatric disorders such as but not limited to dementia, schizophrenia, mania, personality disorders), or the metabolism of the drug (eg, severe renal or hepatic disease); 10. Patient with known hypersensitivity to any CB; 11. Patients unlikely to be available for follow-up (eg, patients from abroad); 12. Patients unlikely to survive as determined by qualified study physicians before randomization; 13. Patients with known CB intake within 3 days prior to TBI.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this “first-in-patient” study is to investigate the pharmacokinetics (PK) and efficacy of 2 dose levels of KN 38 7271 after a 24-hour IV infusion with KN 38 7271 (1 hour accelerated infusion followed by a 23 hour constant rate infusion with a total dose of 1000 µg or 500 µg KN 38 7271) versus placebo given within 4.5 hours of traumatic brain injury (TBI).;Secondary Objective: The secondary objective is to investigate the efficacy and safety of 2 dose levels of KN 38 7271 after a 24-hour IV infusion with KN 38 7271 (1 hour accelerated infusion followed by a 23 hour constant rate infusion with a total dose of 1000 µg or 500 µg KN 38 7271) versus placebo given within 4.5 hours of TBI on clinical outcome and survival.;Primary end point(s): Primary endpoints: - PK of KN 38 7271 (area under the curve [AUC], maximum concentration [Cmax]) after study drug administration (see Table 1) up to 48 hours after start of study medication. - Glasgow Outcome Scale (Extended) (GOSe) - Intracranial pressure (ICP) - Time to achieve a GCS motor score of 6 - Cerebral lesion change in magnetic resonance imaging (MRI) | — |
Countries
Belgium, Czech Republic, Germany
Outcome results
None listed