HypertensionPhase 4NCT01526876
The Effect of Clevidipine on Intracranial Pressure and Cerebral Perfusion Pressure (CCP) in Brain Injured Patients
A Phase 4 study testing clevidipine butyrate in people with Hypertension, run by Columbia University.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypertension
- What is being tested?
- clevidipine butyrate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Nov 2011to 19 Dec 2012
- Phase
- Phase 4
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 -
Who cannot join
- 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.
About this study
Official title: Effect of Clevidipine on Intracranial Pressure, Cerebral Blood Flow, Brain Tissue Oxygenation and Brain Cellular Metabolism in Severely Hypertensive Patients With Acute Brain Injury
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.
Read more
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.
Read the 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.
- Conditions
- Hypertension
- Being tested
- clevidipine butyrate
- Keywords
- Intracranial Pressure, Cerebral Perfusion Pressure, Clevidipine Butyrate
- Medical subject headings
- Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
clevidipine butyrateDrug
Also called Cleviprex
intravenous infusion dose range 1.0 mg/hr - 32 mg/hr titrate to blood pressure effect duration of infusion: 6 hours
| Study group | Role | What they receive |
|---|---|---|
| Single Arm drug study | Experimental | The effect of systemic blood pressure reduction using Clevidipine on intracranial pressure (ICP) and cerebral perfusion pressure (CCP) Receives: Drug: clevidipine butyrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
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).
Measured: Up to 24 hours from the start of infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2012 (estimated)
- Study startNov 2011
- Primary completionNov 2012
- Study completion19 Dec 2012
Why it stopped: Terminated by Sponsor
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypertensionStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- The Medicines Company
- Responsible party
- Sponsor
- Investigators
- Stephan A Mayer, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01526876
- Sponsor's protocol ID
- AAAF4096
- Status last verified
- Jul 2017
- First submitted
- 2 Feb 2012
- Last updated
- 17 Jul 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Clevidipine on Intracranial Pressure, Cerebral Blood Flow, Brain Tissue Oxygenation and Brain Cellular Metabolism in Severely Hypertensive Patients With Acute Brain Injury
- ClinicalTrials.gov ID
- NCT01526876
- Acronym / sponsor ID
- AAAF4096
- Conditions
- Hypertension
- Keywords
- Intracranial Pressure, Cerebral Perfusion Pressure, Clevidipine Butyrate
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Terminated by Sponsor
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- The Medicines Company
- Study start
- Nov 2011
- Primary completion
- Nov 2012 (actual)
- Study completion
- 19 Dec 2012 (actual)
- First posted
- 6 Feb 2012 (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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single Arm drug study | Experimental | Drug: clevidipine butyrateThe effect of systemic blood pressure reduction using Clevidipine on intracranial pressure (ICP) and cerebral perfusion pressure (CCP) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (8 listed)
- 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
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 |
|---|---|---|
| clevidipine butyrateAlso: Cleviprexintravenous infusion dose range 1.0 mg/hr - 32 mg/hr titrate to blood pressure effect duration of infusion: 6 hours | Drug | Single Arm drug study |
Primary outcome
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
1 secondary outcome
"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
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2017.
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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.
Stephan A Mayer, MD principal investigator
Columbia University
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing clevidipine butyrate in people with Hypertension, run by Columbia University.
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 8 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: withdrawn, as of the sponsor's last update on 17 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 was withdrawn before enrolling participants, so there are no results.
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?
Reduction in blood pressure (time frame: Up to 24 hours from the start of clevidipine infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Jul 2017.