Overview

Copenhagen Head Injury Ciclosporin (CHIC) Study

Status:
Completed
Trial end date:
2017-09-21
Target enrollment:
0
Participant gender:
All
Summary
This is an open label study on the pharmacokinetics and safety of ciclosporin in patients with severe traumatic brain injury, who require intensive care unit admission and monitoring of intracranial pressure via a ventricular catheter. 20 patients will be screened, and subsequently enrolled after clinical stabilisation. Thereafter, patients will receive 2.5 mg/kg bolus dose infusion of ciclosporin, followed by either 5 mg/kg/day or 10 mg/kg/day of ciclosporin as continuous infusion for 5 days+3 days monitoring at the intensive care unit. After an additional 30 days, a follow-up phone call will be made to the patient, or the patient's nursing staff, checking patient status and serious adverse events. The two dose levels will be investigated in 10 patients each, starting with the lower dose level for the first 10 patients. Patients will have samples of blood and cerebrospinal fluid drawn at pre-defined time points during the study for pharmacokinetic assessment and evaluation of biomarkers. Bedside monitoring with microdialysis and brain tissue oxygenation will be performed. The safety monitoring includes nephrotoxicity, hepatotoxicity, monitoring of intracranial pressure (ICP), infections monitoring and adverse events collection and reporting.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
NeuroVive Pharmaceutical AB
Treatments:
Cyclosporine
Cyclosporins
Criteria
Inclusion Criteria:

1. Male or female patients, age between 18 and 75 years, inclusive.

2. Requirement for Intensive Care Unit (ICU) admission and clinical indication for
External Ventricular Drainage (EVD) and Intracranial Pressure (ICP) monitoring.

3. Evidence of non-penetrating severe TBI, confirmed by history and abnormalities
consistent with a non-penetrating trauma on computerised tomography (CT) scan upon
admission.

4. Clinical examination with post-resuscitation Glasgow Coma Scale (GCS) of 4-8,
inclusive.

5. Hemodynamically stable after resuscitation (systolic blood pressure (SBP) >100 mm Hg).

6. Informed consent for participation waived: obtained by two independent physicians and
subsequently, the patient's Legally Acceptable Representative (LAR) and General
Practitioner (GP). If GP is unavailable, the Danish Health and Medicines Authority can
give consent together with the LAR.

Exclusion Criteria:

1. Bilaterally fixed dilated pupils.

2. Penetrating traumatic brain injury.

3. Spinal cord injury.

4. Pure epidural haematoma.

5. Currently developed, known or a medical history of renal disorder, significant renal
failure, or high risk renal failure, defined as:

1. Serum creatinine ≥ 1.5 x upper limit of normal (ULN).

2. Pre-existing chronic renal failure with estimated glomerular filtration rate
(eGFR)< 60 ml/min/1.73m2 estimated by the simplified Modification of Diet in
Renal Disease (MDRD) Study formula.

3. Major rhabdomyolysis with serum creatine kinase > 5,000 IU/L.

4. Renal injury resulting in loss of a kidney (either due to direct trauma or
ischaemia).

5. Vascular injury with renal ischaemia likely to cause an episode of acute renal
failure.

6. Any history of renal replacement therapy.

6. Known or a medical history of hepatic disease.

7. Prolonged and/or uncorrectable hypoxia, as judged by the investigator (PaO< 60 mmHg)
or hypotension (SBP< 90 mmHg) upon admission.

8. Suspected or confirmed pregnancy (positive urine sample,followed by confirmational
serum human chorionic gonadotropin (HCG) pregnancy test).

9. Immunosuppression due to drugs (for ex. ciclosporin) or disease (e.g. human
immunodeficiency virus (HIV), malignancy).

10. Known or a medical history of serious chronic viral or fungal infection.

11. Known or a medical history of active mycobacterial infection or antituberculous
treatment.

12. Known or a medical history of any allergic reactions and/or anaphylactic reactions
towards ciclosporin, egg, peanuts or soya-bean proteins.

13. Ongoing preinjury therapy with any of these drugs:

rosuvastatin, tacrolimus, Hypericum perforatum (St.John´s Wort; a herbal dietary
supplement), stiripentol, aliskiren, bosentan, diltiazem, verapamil and
antiepileptics.

14. Participation in other clinical trials.

15. Any significant disease or disorder including abnormal laboratory tests which, in the
opinion of the investigator, may either put the patient at risk because of
participation in the study, or may influence the results of the study