Clevidipine in the Treatment of Patients With Acute Hypertension and Intracerebral Hemorrhage (ACCELERATE)

The Medicines Company

Status and phase

Completed

Phase 3

Conditions

Hypertension

Hemorrhage

Treatments

Drug: clevidipine

Study type

Interventional

Funder types

Industry

Identifiers

NCT00666328

TMC-CLV-07-02

Details and patient eligibility

About

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).

Full description

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.

Enrollment

37 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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