Traumatic Brain InjuryPhase 2CHICNCT01825044
Copenhagen Head Injury Ciclosporin (CHIC) Study
A Phase 2 study testing NeuroSTAT 5 mg/kg/day and NeuroSTAT 10 mg/kg/day in people with Traumatic Brain Injury, run by NeuroVive Pharmaceutical AB at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Traumatic Brain Injury
- What is being tested?
- NeuroSTAT 5 mg/kg/day and NeuroSTAT 10 mg/kg/day
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteDenmark
- Study dates
- Apr 2013to 21 Sep 2017
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Dept. of Neurosurgery, Rigshospitalet, University of Copenhagen
Copenhagen, 2100
About this study
Official title: An 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)
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
- Being tested
- NeuroSTAT 5 mg/kg/day, NeuroSTAT 10 mg/kg/day
- Keywords
- Traumatic Brain Injury, TBI, ciclosporin, pharmacokinetic, safety, microdialysis, mitochondrial protection
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NeuroSTAT 5 mg/kg/dayDrug
Also called Ciclosporin 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
NeuroSTAT 10 mg/kg/dayDrug
Also called Ciclosporin 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
| Study group | Role | What they receive |
|---|---|---|
| NeuroSTAT 5 mg/kg/day | Active comparator | Intravenous bolus of NeuroSTAT (Ciclosporin) 2.5 mg/kg bodyweight followed by 5 days of 5 mg/kg bodyweight/day continuous infusion Receives: Drug: NeuroSTAT 5 mg/kg/day |
| NeuroSTAT 10 mg/kg/day | Active comparator | Intravenous bolus of NeuroSTAT (Ciclosporin) 2.5 mg/kg bodyweight followed by 5 days of 10 mg/kg bodyweight/day continuous infusion Receives: Drug: NeuroSTAT 10 mg/kg/day |
What is being measured
The primary outcome is the main question the study is designed to answer.
Non-compartmental analysis of pharmacokinetics (PK) of Ciclosporin in whole blood
Peak Plasma Concentration (Cmax) of Ciclosporin and Area under the blood concentration versus time curve (AUC) of Ciclosporin. This will characterise the pharmacokinetic profile of the two chosen dosing regimens of ciclosporin in severe Traumatic Brain Injury (TBI) patients.
Measured: Prespecified timepoints during 8 days (PK)
Incidence of adverse events
Including:
- Ciclosporin levels in whole blood.
- Markers of nephrotoxicity: plasma creatinine plasma Cystatin-C and blood urea nitrogen.
- Markers of hepatotoxicity: prothrombin time (PT), aspartate transaminase (AST), alanine transaminase (ALT) and bilirubin.
- Intracranial Pressure (ICP)
- Assessment of infections: according to standard procedures at intensive care unit.
Measured: 38 days
Secondary outcomes (2)
Ciclosporin levels in cerebrospinal fluid (CSF)
The CSF samples will be drawn from the EVD-catheter at the same time points as in blood to document central nervous system penetration of ciclosporin
Measured: Prespecified timepoints during 8 days
Safety biomarkers for nephrotoxicity
Kidney Injury Molecule (KIM)-1, creatinine and Cystatin-C in urine samples
Measured: Measured at prespecified timepoints during 8 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2013 (estimated)
- Study startApr 2013
- Primary completion21 Sep 2017
- Study completion21 Sep 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- NeuroVive Pharmaceutical AB
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jesper Kelsen, MD., PhD, Principal investigator, Dept. of Neurosurgery, Rigshospitalet, Copenhagen, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01825044
- Sponsor's protocol ID
- 2012.001
- Other IDs
- 2012-000756-34
- Acronym
- CHIC
- Status last verified
- Oct 2017
- First submitted
- 20 Mar 2013
- Last updated
- 4 Oct 2017
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 37561274
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An 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)
- ClinicalTrials.gov ID
- NCT01825044
- Acronym / sponsor ID
- CHIC / 2012.001
- Conditions
- Traumatic Brain Injury
- Keywords
- Traumatic Brain Injury, TBI, ciclosporin, pharmacokinetic, safety, microdialysis, mitochondrial protection
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- NeuroVive Pharmaceutical ABIndustry (pharma, biotech, devices)
- Study start
- Apr 2013 (actual)
- Primary completion
- 21 Sep 2017 (actual)
- Study completion
- 21 Sep 2017 (actual)
- First posted
- 5 Apr 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Factorial
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| NeuroSTAT 5 mg/kg/day | Active comparator | Drug: NeuroSTAT 5 mg/kg/dayIntravenous 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 | Active comparator | Drug: NeuroSTAT 10 mg/kg/dayIntravenous bolus of NeuroSTAT (Ciclosporin) 2.5 mg/kg bodyweight followed by 5 days of 10 mg/kg bodyweight/day continuous infusion |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (22 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NeuroSTAT 5 mg/kg/dayAlso: Ciclosporin 5 mg/kg/dayIntravenous bolus of NeuroSTAT (Ciclosporin) 2.5 mg/kg bodyweight followed by 5 days of 5 mg/kg bodyweight/day continuous infusion | Drug | NeuroSTAT 5 mg/kg/day |
| NeuroSTAT 10 mg/kg/dayAlso: Ciclosporin 10 mg/kg/dayIntravenous bolus of NeuroSTAT (Ciclosporin) 2.5 mg/kg bodyweight followed by 5 days of 10 mg/kg bodyweight/day continuous infusion | Drug | NeuroSTAT 10 mg/kg/day |
Primary outcome
Non-compartmental analysis of pharmacokinetics (PK) of Ciclosporin in whole blood
Time frame: Prespecified timepoints during 8 days (PK)
Peak Plasma Concentration (Cmax) of Ciclosporin and Area under the blood concentration versus time curve (AUC) of Ciclosporin. This will characterise the pharmacokinetic profile of the two chosen dosing regimens of ciclosporin in severe Traumatic Brain Injury (TBI) patients.
Incidence of adverse events
Time frame: 38 days
Including: 1. Ciclosporin levels in whole blood. 2. Markers of nephrotoxicity: plasma creatinine plasma Cystatin-C and blood urea nitrogen. 3. Markers of hepatotoxicity: prothrombin time (PT), aspartate transaminase (AST), alanine transaminase (ALT) and bilirubin. 4. Intracranial Pressure (ICP) 5. Assessment of infections: according to standard procedures at intensive care unit.
2 secondary outcomes
Ciclosporin levels in cerebrospinal fluid (CSF)
Time frame: Prespecified timepoints during 8 days
Safety biomarkers for nephrotoxicity
Time frame: Measured at prespecified timepoints during 8 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2017.
- Derived from this study: PubMed 37561274Hansson 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jesper Kelsen, MD., PhD principal investigator
Dept. of Neurosurgery, Rigshospitalet, Copenhagen, Denmark
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing NeuroSTAT 5 mg/kg/day and NeuroSTAT 10 mg/kg/day in people with Traumatic Brain Injury, run by NeuroVive Pharmaceutical AB at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Non-compartmental analysis of pharmacokinetics (PK) of Ciclosporin in whole blood (time frame: Prespecified timepoints during 8 days (PK)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01825044, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2017.