Copenhagen Head Injury Ciclosporin (CHIC) Study (CHIC)

October 2, 2017 updated by: NeuroVive Pharmaceutical AB

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
      • Copenhagen, Denmark, 2100
        • Dept. of Neurosurgery, Rigshospitalet, University of Copenhagen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 75 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: FACTORIAL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
ACTIVE_COMPARATOR: 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
Drug: 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
Other Names:
  • Ciclosporin 5 mg/kg/day
ACTIVE_COMPARATOR: 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
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
Other Names:
  • Ciclosporin 10 mg/kg/day

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Prespecified timepoints during 8 days (PK)
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.
38 days

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Ciclosporin levels in cerebrospinal fluid (CSF)
Time Frame: Prespecified timepoints during 8 days
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
Prespecified timepoints during 8 days
Safety biomarkers for nephrotoxicity
Time Frame: Measured at prespecified timepoints during 8 days
Kidney Injury Molecule (KIM)-1, creatinine and Cystatin-C in urine samples
Measured at prespecified timepoints during 8 days

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Electroencephalography (EEG).
Time Frame: During 8 days
The background pattern will be interpreted and analysed by an EEG program. The aim is to find evidence if EEG analyses could be used to predict clinical outcome.
During 8 days
Biomarkers of brain injury in brain tissue
Time Frame: Measured at prespecified timepoints during 8 days
Microdialysis in the most and least traumatised side pre-treatment and every second hour until the end of day 8
Measured at prespecified timepoints during 8 days
Brain tissue oxygen
Time Frame: During 8 days
Continuously (every 5th second) measured directly using an indwelling probe.
During 8 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
NeuroVive Pharmaceutical AB

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jesper Kelsen, MD., PhD, Dept. of Neurosurgery, Rigshospitalet, Copenhagen, Denmark

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 1, 2013

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 21, 2017

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 21, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 20, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 2, 2013

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 5, 2013

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 4, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 2, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2012.001
  • 2012-000756-34 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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