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

NCT01526876 | Withdrawn Phase 4

• 1 other identifier: AAAF4096
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hypertension

Keywords

Intracranial Pressure; Cerebral Perfusion Pressure; Clevidipine Butyrate

Outcome Measures

Primary Outcomes (1)

• Reduction in blood pressure

  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

  Up to 24 hours from the start of clevidipine infusion

Secondary Outcomes (1)

• "Time to target" (below the CCP threshold and Percent time within the target CCP range)

  Up to 24 hours from the start of infusion

Study Arms (1)

Single Arm drug study

EXPERIMENTAL

The effect of systemic blood pressure reduction using Clevidipine on intracranial pressure (ICP) and cerebral perfusion pressure (CCP)

Drug: clevidipine butyrate

Interventions

clevidipine butyrate DRUG

intravenous infusion dose range 1.0 mg/hr - 32 mg/hr titrate to blood pressure effect duration of infusion: 6 hours

Also known as: Cleviprex

Single Arm drug study

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Coma (Glasgow Coma Scale (GCS) less than or equal to 8) due to any cause
• Male and Female patients \> 18 years.
• Mechanically ventilated
• Functional multimodality neuromonitoring bundle (intracranial pressure (ICP) monitor, Hemedex, Licox, and microdialysis) placed in the course of routine clinical management
• 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
• Patient has a minimum of 60 min of baseline brain multimodality monitoring prior to initiation of clevidipine -

You may not qualify if:

• Absence of negative pregnancy test in women of child-bearing potential.
• FiO2 \>50%
• Unable to maintain stable sedative infusion rates for 4 hours
• Unable to maintain stable ventilator setting for 4 hours
• Unable to maintain stable insulin infusion rates for 4 hours
• Patient is currently receiving nicardipine infusion
• Allergy to soybean oil or lecithin
• Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of enrollment.

Sponsors & Collaborators

• Columbia University: lead
• The Medicines Company: collaborator

MeSH Terms

Conditions

Hypertension

Interventions

clevidipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Stephan A Mayer, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2012
• First Posted: February 6, 2012
• Study Start: November 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: December 19, 2012
• Last Updated: July 17, 2017

Record last verified: 2017-07