CHICAn Open-label, Uncontrolled Phase II-study to Investigate Pharmacokinetics, Safety and Biomarkers of Effectiveness of NeuroSTAT® (Ciclosporin) in Patients With Severe Traumatic Brain Injury (TBI)

Fecha de inicio: 1 de abril de 2013

Inclusion Criteria: Male or female patients, age between 18 and 75 years, inclusive. Requirement for Intensive Care Unit (ICU) admission and clinical indication for External Ventricular Drainage (EVD) and Intracranial Pressure (ICP) monitoring. Evidence of non-penetrating severe TBI, confirmed by history and abnormalities consistent with a non-penetrating trauma on computerised tomography (CT) scan upon admission. Clinical examination with post-resuscitation Glasgow Coma Scale (GCS) of 4-8, inclusive. Hemodynamically stable after resuscitation (systolic blood pressure (SBP) >100 mm Hg). 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: Bilaterally fixed dilated pupils. Penetrating traumatic brain injury. Spinal cord injury. Pure epidural haematoma. Currently developed, known or a medical history of renal disorder, significant renal failure, or high risk renal failure, defined as: Serum creatinine ≥ 1.5 x upper limit of normal (ULN). 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. Major rhabdomyolysis with serum creatine kinase > 5,000 IU/L. Renal injury resulting in loss of a kidney (either due to direct trauma or ischaemia). Vascular injury with renal ischaemia likely to cause an episode of acute renal failure. Any history of renal replacement therapy. Known or a medical history of hepatic disease. Prolonged and/or uncorrectable hypoxia, as judged by the investigator (PaO< 60 mmHg) or hypotension (SBP< 90 mmHg) upon admission. Suspected or confirmed pregnancy (positive urine sample,followed by confirmational serum human chorionic gonadotropin (HCG) pregnancy test). Immunosuppression due to drugs (for ex. ciclosporin) or disease (e.g. human immunodeficiency virus (HIV), malignancy). Known or a medical history of serious chronic viral or fungal infection. Known or a medical history of active mycobacterial infection or antituberculous treatment. Known or a medical history of any allergic reactions and/or anaphylactic reactions towards ciclosporin, egg, peanuts or soya-bean proteins. 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. Participation in other clinical trials. 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