Cerebral oedema caused by traumatic brain injury (TBI) MedDRA version: 20.1 Level: LLT Classification code 10060690 Term: Traumatic brain injury System Organ Class: 100000004863 MedDRA version: 20.1 Level: LLT Classification code 10008127 Term: Cerebral oedema System Organ Class: 100000004852
Conditions
Interventions
Product Code: AF-16
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: not available
CAS Number: 188585-60-6
Other descriptive name: AF-16
Concentration unit: mg/ml milligram(s)/millilit
Sponsors
Lantmännen Medical AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Is a male or female adult = 18 through = 85 years of age 2. Has been admitted to the hospital because of a TBI within 12 hours of injury 3. Has a GCS score between 4 and 12 (inclusive) that requires ICP monitoring 4. Shows signs of cerebral edema (brain swelling) on the CT scan at admission 5. Has ICP monitoring in place before first dose of AF-16 6. Has a non-provoked elevation of ICP above the threshold value of 15 mm Hg during the 1 hour before the administration of AF-16 7. Has a systolic blood pressure = 100 mm Hg 8. Has provided signed informed consent (through the patient’s representative according to local regulatory requirements and in accordance with the study protocol) Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 8 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 4
Exclusion criteria
Exclusion criteria: 1. Has a completely effaced basal cistern and midline shift > 5 mm on the admission CT scan unless the midline shift is a consequence of a focal lesion 2. Has received surgical interventions to manage ICP elevation before enrollment unless: i. ICP monitoring continues postoperatively, and ii. ICP > 15 mm Hg in the postoperative period that is not due to re-accumulation of a surgical lesion 3. Is planned to have decompressive craniectomy before enrollment 4. Has an extradural hemorrhage evaluated to be the sole cause of ICP increase without signs of cerebral edema 5. Has extensive thoracic, abdominal, or pelvic trauma that requires surgical interventions 6. Has a penetrating head injury (eg, missile, stab wound) 7. Has associated spinal injury 8. Is not expected to survive > 24 hours after admission 9. Has had a cardiopulmonary resuscitation performed post-injury 10. Has continuous bleeding that is likely to require multiple transfusions (> 4 units of red blood cells) 11. Is in a coma suspected to be primarily due to other causes than head injury (eg, drug overdose) 12. Has known or CT scan evidence of preexisting major cerebral damage 13. Has a known allergy to any of the AF-16 components 14. Is a pregnant female* 15. Is otherwise unsuitable for study participation as judged by the investigator *as evidenced by a positive human chorionic gonadotropin (hCG) test in the urine. A pregnancy test will be conducted in all women potentially being of childbearing potential. For the purpose of this study, this includes all women below 60 years. The result of a pregnancy test will not be revealed to the representative giving consent to study participation on behalf of the woman.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary Objective: • To evaluate the safety and tolerability of 5 days of antisecretory factor AF-16 treatment in patients with cerebral edema (brain swelling) because of TBI.;Secondary Objective: Secondary Objectives: • To explore the efficacy of 5 days of AF-16 treatment compared with historical controls as measured by intracranial pressure (ICP) in patients with cerebral edema (brain swelling) because of TBI. • To explore the use of concomitant therapies (therapy intensity level [TIL]) after 5 days of AF-16 treatment compared with historical controls in patients with cerebral edema (brain swelling) because of TBI.;Primary end point(s): Primary endpoint: • Frequency and severity of adverse events (AEs) in patients treated with AF-16;Timepoint(s) of evaluation of this end point: Continuously from enrolment (Day 1) until Follow-up on Day 30. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: • Changes in vital signs, physical examination results, electrocardiogram, clinical chemistry, hematology, coagulation, and hormonal values during the study period • TIL area under the curve (AUC) from Day 1 through Day 5 or earlier in the case of early discontinuation • Total time spent with insults of ICP >20 mm Hg lasting longer than 5 minutes from the start of AF-16 treatment to the end of AF-16 treatment (ie, Day 5 or earlier in the case of early discontinuation) • ICP AUC24 from Day 1 through Day 5 or earlier in the case of early discontinuation • Use of third-tier therapies/high-TIL treatments (temperature <35?, secondary decompressive craniotomy, metabolic suppression [eg, with barbiturates]), or incidence of death;Timepoint(s) of evaluation of this end point: Changes in vital signs, ECG, physical examination, safety laboratory values will be followed on a daily basis during study days 1-7, on Day 14 and on Day 30. Hormonal values will be measured at enrolment and on days 7,14 and 30. TIL and its subitems will be reported every 24 hours, ICP will be reported every 2 hours. | — |
Countries
France, Germany
Contacts
Public ContactLars Franzén
Lantmännen Medical AB
Outcome results
None listed