Copenhagen Head Injury Ciclosporin (CHIC) Study

NCT ID: NCT01825044

Last Updated: 2017-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2017-09-21

Brief 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.

Conditions

Traumatic Brain Injury

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

NeuroSTAT 5 mg/kg/day

Intravenous bolus of NeuroSTAT (Ciclosporin) 2.5 mg/kg bodyweight followed by 5 days of 5 mg/kg bodyweight/day continuous infusion

Group Type: ACTIVE_COMPARATOR

NeuroSTAT 5 mg/kg/day

Intervention Type: DRUG

Intravenous bolus of NeuroSTAT (Ciclosporin) 2.5 mg/kg bodyweight followed by 5 days of 5 mg/kg bodyweight/day continuous infusion

NeuroSTAT 10 mg/kg/day

Intravenous bolus of NeuroSTAT (Ciclosporin) 2.5 mg/kg bodyweight followed by 5 days of 10 mg/kg bodyweight/day continuous infusion

Group Type: ACTIVE_COMPARATOR

NeuroSTAT 10 mg/kg/day

Intervention Type: DRUG

Intravenous bolus of NeuroSTAT (Ciclosporin) 2.5 mg/kg bodyweight followed by 5 days of 10 mg/kg bodyweight/day continuous infusion

Interventions

NeuroSTAT 5 mg/kg/day

Intravenous bolus of NeuroSTAT (Ciclosporin) 2.5 mg/kg bodyweight followed by 5 days of 5 mg/kg bodyweight/day continuous infusion

Intervention Type: DRUG

NeuroSTAT 10 mg/kg/day

Intravenous bolus of NeuroSTAT (Ciclosporin) 2.5 mg/kg bodyweight followed by 5 days of 10 mg/kg bodyweight/day continuous infusion

Intervention Type: DRUG

Other Intervention Names

Ciclosporin 5 mg/kg/day; Ciclosporin 10 mg/kg/day

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

NeuroVive Pharmaceutical AB

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jesper Kelsen, MD., PhD

Role: PRINCIPAL_INVESTIGATOR

Dept. of Neurosurgery, Rigshospitalet, Copenhagen, Denmark

Locations

Dept. of Neurosurgery, Rigshospitalet, University of Copenhagen

Copenhagen, , Denmark

Countries

Denmark

References

Hansson MJ, Elmer E. Cyclosporine as Therapy for Traumatic Brain Injury. Neurotherapeutics. 2023 Oct;20(6):1482-1495. doi: 10.1007/s13311-023-01414-z. Epub 2023 Aug 10.

Reference Type: DERIVED

PMID: 37561274 (View on PubMed)

Other Identifiers

2012-000756-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2012.001

Identifier Type: -

Identifier Source: org_study_id