Clevidipine in the Treatment of Patients With Acute Hypertension and Intracerebral Hemorrhage (ACCELERATE)
Clevidipine in the Treatment of Patients With Acute Hypertension and Intracerebral Hemorrhage (ACCELERATE)
The purpose of this study was 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 was 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 was obtained from patients meeting the inclusion criteria before the
 initiation of any study-specific procedures. At screening, a clinical and neurological
 examination was carried out. For the purposes of this study, acute hypertension was defined
 as SBP >160 mmHg immediately prior to initiation of study drug. Approximately 30 to 40
 patients with acute intracerebral hemorrhage (ICH) were planned to be enrolled with
 approximately 10 patients requiring monitoring of intracranial pressure (ICP). Infusion of
 study drug was initiated within 12 hours of ICH symptom onset. All eligible patients enrolled
 received clevidipine in an open label manner. Clevidipine was to be infused at an initial
 rate of 2.0 mg/h for the first 1.5 minutes. Thereafter, titration to higher infusion rates
 were to be attempted as needed, to obtain the target SBP range (SBP ≤160 mmHg to ≥140 mmHg).
 Titration to effect was 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) was attained. During the
 first 30 minutes, if the desired blood pressure lowering effect was not attained or
 maintained, an alternative intravenous (IV) antihypertensive agent(s), advised to be a
 different class other than calcium channel blockers, could be used with or without stopping
 the clevidipine infusion. The clevidipine infusion could continue for up to a maximum of 96
 hours. Twenty-four hour follow-up computerized tomography (CT) scan results were recorded,
 including measurement of intracerebral hematoma volumes. Assessment of safety was performed
 throughout the treatment period and until 6 hours after termination of study drug. Patients
 were followed for 7 days following termination of the clevidipine infusion.
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
 were enrolled if SBP at the time of enrollment was ≤160 mmHg

 -  Required antihypertensive therapy to achieve systolic blood pressure ≤160 mmHg

 -  Written informed consent obtained

 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 was permitted. ICP-monitored patients enrolled in the sub-study could 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 would 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