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

NCT ID: NCT00666328

Last Updated: 2014-08-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2010-04-30

Brief Summary

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).

Detailed 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.

Conditions

Hypertension; Hemorrhage

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

clevidipine

This will be a single-arm study with no reference therapy.

Group Type: EXPERIMENTAL

clevidipine

Intervention Type: DRUG

Clevidipine injectable emulsion (0.5 mg/mL) in 20% lipid emulsion in 100 mL bottles was administered intravenously to all patients via a single dedicated line.

Clevidipine was 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 systolic blood pressure (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. The clevidipine infusion rate could be increased or decreased to maintain systolic blood pressure for up to a maximum of 96 hours.

Interventions

clevidipine

Clevidipine injectable emulsion (0.5 mg/mL) in 20% lipid emulsion in 100 mL bottles was administered intravenously to all patients via a single dedicated line.

Clevidipine was 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 systolic blood pressure (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. The clevidipine infusion rate could be increased or decreased to maintain systolic blood pressure for up to a maximum of 96 hours.

Intervention Type: DRUG

Other Intervention Names

clevidipine injectable emulsion; clevidipine emulsion; Cleviprex

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Medicines Company

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Carmelo Graffagnino, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Washington Hospital Center

Washington D.C., District of Columbia, United States

The Queens Medical Center

Honolulu, Hawaii, United States

The John Hopkins Hospital

Baltimore, Maryland, United States

Maine Medical Center

Portland, Massachusetts, United States

Henry Ford Hospital

Detroit, Michigan, United States

Columbia University Medical Center

New York, New York, United States

Duke University Medical Center

Durham, North Carolina, United States

Guilford Neurologic - Moses H Cone Health System

Greensboro, North Carolina, United States

Cleveland Clinic Hospitals

Cleveland, Ohio, United States

The Ohio State University

Columbus, Ohio, United States

Thomas Jefferson University Stroke Research

Philadelphia, Pennsylvania, United States

Medical University of South Carolina

Charleston, South Carolina, United States

The University Health Science Center at S.A.

San Antonio, Texas, United States

Intermountain Medical Center

Murray, Utah, United States

Universitätsklinikum Leipzig

Liebigstraße 22a, Leipzig, Germany

Universitatsklinikum Erlangen

Erlangen, , Germany

Universitatsklinikum Heidelberg

Heidelberg, , Germany

Countries

United States; Germany

Other Identifiers

TMC-CLV-07-02

Identifier Type: -

Identifier Source: org_study_id