• The percentage of patients who reach a systolic blood pressure of ≤160 mmHg within 30 minutes of the initiation of clevidipine infusion [ Time Frame: Within 30 minutes of the initiation of study drug infusion ] [ Designated as safety issue: No ]
• Percent change from baseline in systolic blood pressure during the initial 30 minutes of clevidipine infusion [ Time Frame: During the initial 30 minutes of study drug infusion ] [ Designated as safety issue: No ]
• Magnitude, frequency and duration of systolic blood pressure excursions (calculated as area under the curve) outside the target range normalized per hour for the duration of the clevidipine monotherapy infusion [ Time Frame: Duration of the study drug infusion (up to 96 hours) ] [ Designated as safety issue: No ]
• Percent time blood pressures were maintained within the target range (systolic blood pressure ≤160 mmHg to ≥140 mmHg) over each 24 hours during monotherapy infusion of clevidipine [ Time Frame: Every 24 hours (for up to 96 hours) ] [ Designated as safety issue: No ]
• Mean and median dose of clevidipine during the treatment period [ Time Frame: Up to 96 hours ] [ Designated as safety issue: No ]
• Proportion of patients requiring the addition of an alternative antihypertensive agent(s) with or without clevidipine [ Time Frame: Up to 96 hours ] [ Designated as safety issue: No ]
• Percent change in heart rate during the initial 30 minutes of clevidipine infusion [ Time Frame: During initial 30 minutes of study drug infusion ] [ Designated as safety issue: Yes ]
• The percentage of patients whose systolic blood pressure is <90 mmHg within 30 minutes of the initiation of clevidipine infusion [ Time Frame: Within 30 minutes of the initiation of study drug infusion ] [ Designated as safety issue: Yes ]
• Safety of a prolonged infusion of clevidipine (up to 96 hours) [ Time Frame: Up to 7 days following termination of study drug infusion ] [ Designated as safety issue: Yes ]

• The percentage of patients who reach a systolic blood pressure of ≤160 mmHg within 30 minutes of the initiation of clevidipine infusion [ Time Frame: Within 30 minutes of the initiation of study drug infusion ] [ Designated as safety issue: No ]
• Percent change from baseline in systolic blood pressure during the initial 30 minutes of clevidipine infusion [ Time Frame: During the initial 30 minutes of study drug infusion ] [ Designated as safety issue: No ]
• Magnitude, frequency and duration of systolic blood pressure excursions (calculated as area under the curve) outside the target range normalized per hour for the duration of the clevidipine monotherapy infusion [ Time Frame: Duration of the study drug infusion (up to 96 hours) ] [ Designated as safety issue: No ]
• Percent time blood pressures were maintained within the target range (systolic blood pressure ≤160 mmHg to ≥140 mmHg) over each 24 hours during monotherapy infusion of clevidipine [ Time Frame: Every 24 hours (for up to 96 hours) ] [ Designated as safety issue: No ]
• Mean and median dose of clevidipine during the treatment period [ Time Frame: Up to 96 hours ] [ Designated as safety issue: No ]
• Proportion of patients requiring the addition of an alternative antihypertensive agent(s) with or without clevidipine [ Time Frame: Up to 96 hours ] [ Designated as safety issue: No ]
• Percent change in heart rate during the initial 30 minutes of clevidipine infusion [ Time Frame: During initial 30 minutes of study drug infusion ] [ Designated as safety issue: Yes ]
• The percentage of patients whose systolic blood pressure is less than <90 mmHg within 30 minutes of the initiation of clevidipine infusion [ Time Frame: Within 30 minutes of the initiation of study drug infusion ] [ Designated as safety issue: Yes ]
• Safety of a prolonged infusion of clevidipine (up to 96 hours) [ Time Frame: Up to 7 days following termination of study drug infusion ] [ Designated as safety issue: Yes ]

The purpose of this study is to determine the efficacy and safety of clevidipine for treating acute hypertension (high blood pressure, defined as systolic blood pressure >160 mmHg) in patients with intracerebral hemorrhage (i.e., bleeding in the brain; stroke).

This is a multicenter, single-arm, non-blinded dose titration efficacy and safety trial evaluating the ability of clevidipine, a vascular-selective L-type calcium channel antagonist, to rapidly control acute hypertension in patients with intracerebral hemorrhage. Informed consent will be obtained from patients meeting the inclusion criteria before the initiation of any study-specific procedures. At screening a clinical and neurological examination will be carried out. For the purposes of this study, acute hypertension will be defined as SBP >160 mmHg immediately prior to initiation of study drug. Approximately 30 to 40 patients with acute ICH will be enrolled with approximately 10 patients requiring ICP monitoring. Infusion of study drug will be initiated within 12 hours of ICH symptom onset. All eligible patients will be enrolled to receive clevidipine in an open label manner. Clevidipine will be infused at an initial rate of 2.0 mg/h for the first 1.5 minutes. Thereafter, titration to higher infusion rates can be attempted as needed to obtain the target SBP range (SBP ≤160 mmHg to ≥140 mmHg). Titration to effect is to proceed by doubling the dose every 1.5 minutes, up to a maximum of 32.0 mg/h, until the desired effect (SBP within the target range) is attained. Clevidipine infusion may continue for up to a maximum of 96 hours. Twenty-four hour follow-up CT scan results will be recorded, including measurement of intracerebral hematoma volumes. Assessment of safety will be performed throughout the treatment period and until 6 hours after termination of study drug. Patients will be followed for 7 days following termination of the clevidipine infusion.

• Hypertension
• Hemorrhage

Inclusion Criteria:

• CT evidence of intracerebral hemorrhage (diagnosis and treatment within 12 hours of symptom onset)
• Age 18 years or older
• Baseline systolic blood pressure (immediately prior to initiation of clevidipine) >160 mmHg measured using an arterial line. ICP-monitored patients enrolled in the sub-study may be enrolled if SBP at the time of enrollment is ≤160 mmHg
• Requires antihypertensive therapy to achieve systolic blood pressure ≤160 mmHg
• Written informed consent

Exclusion Criteria:

• Decision for early surgical evacuation prior to 30 minutes of clevidipine
• Receipt of an oral antihypertensive within 2 hours prior to initiation of clevidipine
• Treatment with a continuous infusion of an IV antihypertension agent prior to initiation of clevidipine. Bolus treatment with urapidil (Germany only), labetalol or hydralazine is permitted. ICP-monitored patients enrolled in the sub-study may be enrolled with a continuous infusion of an IV antihypertensive agent prior to the initiation of clevidipine
• Intracerebral hematoma considered to be related to trauma by the neurologist or neurosurgeon
• Aneurysmal sub-arachnoid hemorrhage
• Glasgow coma score of <5 and fixed dilated pupils
• Expectation that the patient will not tolerate or require intravenous antihypertensive therapy for a minimum of 30 minutes
• Known or suspected aortic dissection
• Acute myocardial infarction on presentation
• Positive pregnancy test or known pregnancy
• Intolerance or allergy to calcium channel blockers
• Allergy to soybean oil or egg lecithin
• Known liver failure, cirrhosis or pancreatitis
• Prior directives against advanced life support
• Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of enrollment