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The Effect of Clevidipine on Intracranial Pressure and Cerebral Perfusion Pressure (CCP) in Brain Injured Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01526876
Recruitment Status : Withdrawn (Terminated by Sponsor)
First Posted : February 6, 2012
Last Update Posted : July 17, 2017
Sponsor:
Collaborator:
The Medicines Company
Information provided by (Responsible Party):
Columbia University

Tracking Information
First Submitted Date  ICMJE February 2, 2012
First Posted Date  ICMJE February 6, 2012
Last Update Posted Date July 17, 2017
Study Start Date  ICMJE November 2011
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 3, 2012)
Reduction in blood pressure [ Time Frame: Up to 24 hours from the start of clevidipine infusion ]
Systemic Blood Pressure will be monitored every minute for the first 30 mins, at 45 and 6 mins and then hourly for 6 hours of treatment. ICP will be monitored every 5 minutes from start of infusion up to 6 hours of treatment
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT01526876 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 3, 2012)
"Time to target" (below the CCP threshold and Percent time within the target CCP range) [ Time Frame: Up to 24 hours from the start of infusion ]
Will be looking at the "Time to target" (below the CCP threshold and Percent time within the target CCP range) to assess whether clevidipine is safe and effective for rapidly controlling blood pressure to achieve desired cerebral perfusion pressure (CCP).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Effect of Clevidipine on Intracranial Pressure and Cerebral Perfusion Pressure (CCP) in Brain Injured Patients
Official Title  ICMJE Effect of Clevidipine on Intracranial Pressure, Cerebral Blood Flow, Brain Tissue Oxygenation and Brain Cellular Metabolism in Severely Hypertensive Patients With Acute Brain Injury
Brief Summary

Patients with acute brain injury are at risk for complications such as increased pressure in the brain (intracranial pressure (ICP)), decreased blood flow, bleeding, and brain swelling (cerebral edema). Several studies have suggested that high blood pressure is associated with a worsening outcome possibly due to an increased rate of continued bleeding or rebleeding, as well as increased brain swelling (cerebral edema). High systemic (body) blood pressure (SBP) may also increase the risk of ongoing bleeding. Therefore lowering the blood pressure (BP) is critical, as continued bleeding occurs most frequently in patients with high BP.

Clevidipine Butyrate (Cleviprex) is a new medication approved by the FDA for the treatment of acute high blood pressure (hypertension). Cleviprex is given through an intravenous line (IV) and has the benefit of being faster acting and easier to control adjustments than other drugs used to treat high BP. Patients who have an acute brain injury and who have severe high BP may benefit from this faster acting medication.

For this study, eligible patients, 18 yrs of age or older, will have been admitted to the Neurocritical care unit within 24 hours after their brain injury, who have high systemic (body) SBP. The treating physicians will have already had multimodality brain monitoring placed for clinical management of the patient (standard care).

The investigators will use Cleviprex to lower their SBP and record brain pressure and brain blood flow measurements from the multimodality monitoring. Due to the severity of their brain injury most of the patients eligible for the study will be unable to provide consent. Informed consent will be sought from a surrogate (family member, spouse or close friend) according to Columbia University Medical Center guidelines.

Cleviprex is fast acting and effects are seen in about 90 seconds. The medication will be started at a low rate, and if the SBP still needs lowering, the dose increased every 90 seconds until the maximum FDA approved dose is reached. If the SBP is still high, another medication used to treat high blood pressure will be added (Cardene or labetolol).

Once the SBP is lowered and is stable, the Cleviprex will be continued for 6 hours. As part of standard care, patients have their blood pressure monitored continuously. After 6 hours the treating physician will make a determination to continue clinical management with cleviprex or another antihypertensive medication.

Detailed Description

This is an open-label, single arm, single center study in patients with hypertension in the setting of an acute brain injury. Approximately 15 patients admitted to the Columbia University Neurocritical Care Unit with intracerebral hemorrhage, subarachnoid hemorrhage or traumatic brain injury who are hypertensive and have neuromonitoring probes placed in the course of standard clinical management will be enrolled over a 10-12 month period. Patients must be hypertensive (SBP > 180mmHg), or have an elevated cerebral perfusion pressure (CPP) above 100 mm Hg and the decision has been made by the ICU team to initiate an infusion of clevidipine to maintain CPP within a target range of 70-90 mm Hg and SBP between 120-180mmHg.

Due to the decreased level of consciousness from their injury, the majority of patients will be unable to provide consent. Informed consent will be sought from a surrogate according to Columbia University Medical Center (CUMC) guidelines (See section 8-Informed Consent Process).

Clevidipine infusion will be used to treat hypertension within the first 24 hours after injury. Multi-modality brain monitoring will have been placed as standard care.

Clevidipine will be infused at an initial rate of 2.0 mg/h for the first 90 seconds and titrated to effect (CPP target range of 70-90 mm Hg) by either doubling or reducing the dose by 50% every 90 seconds (with dose ranging 0-32mg/h of continuous IV infusion).

At the end of 6 hours clevidipine treatment, the treating physician will make a determination to continue clinical management with clevidipine or change to another antihypertensive medication.

Patients will be monitored at 24 hours after infusion for liver function, triglycerides and lipase.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hypertension
Intervention  ICMJE Drug: clevidipine butyrate
intravenous infusion dose range 1.0 mg/hr - 32 mg/hr titrate to blood pressure effect duration of infusion: 6 hours
Other Name: Cleviprex
Study Arms  ICMJE Experimental: Single Arm drug study
The effect of systemic blood pressure reduction using Clevidipine on intracranial pressure (ICP) and cerebral perfusion pressure (CCP)
Intervention: Drug: clevidipine butyrate
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: February 26, 2013)
0
Original Estimated Enrollment  ICMJE
 (submitted: February 3, 2012)
15
Actual Study Completion Date  ICMJE December 19, 2012
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Coma (Glasgow Coma Scale (GCS) less than or equal to 8) due to any cause
  2. Male and Female patients > 18 years.
  3. Mechanically ventilated
  4. Functional multimodality neuromonitoring bundle (intracranial pressure (ICP) monitor, Hemedex, Licox, and microdialysis) placed in the course of routine clinical management
  5. Patient is hypertensive at the time of enrollment (CPP >100 mm Hg and/or SBP >180mmHg) and the decision has been made to start clevidipine butyrate in order to maintain CPP within 70-90 mm Hg and/or SBP <180mmHg
  6. Patient has a minimum of 60 min of baseline brain multimodality monitoring prior to initiation of clevidipine -

Exclusion Criteria:

  1. Absence of negative pregnancy test in women of child-bearing potential.
  2. FiO2 >50%
  3. Unable to maintain stable sedative infusion rates for 4 hours
  4. Unable to maintain stable ventilator setting for 4 hours
  5. Unable to maintain stable insulin infusion rates for 4 hours
  6. Patient is currently receiving nicardipine infusion
  7. Allergy to soybean oil or lecithin
  8. Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of enrollment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT01526876
Other Study ID Numbers  ICMJE AAAF4096
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Columbia University
Study Sponsor  ICMJE Columbia University
Collaborators  ICMJE The Medicines Company
Investigators  ICMJE
Principal Investigator: Stephan A Mayer, MD Columbia University
PRS Account Columbia University
Verification Date July 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP