Clinical trial NCT00666328: Clevidipine in the Treatment of Patients With Acute Hypertension and Intracerebral Hemorrhage (ACCELERATE)
Official title: The Evaluation of Patients With Acute Hypertension and Intracerebral Hemorrhage With Intravenous Clevidipine Treatment (ACCELERATE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Hemorrhage
Keywords: Hypertension
Hemorrhage
Intracranial Pressure
Antihypertensive Agent
Calcium Channel Blocker
Lead sponsor: The Medicines Company
Sponsor class: INDUSTRY
First posted: 2008-04-24
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Median Time to Achieve Target SBP Range (≤160 mmHg to ≥140 mmHg) Within 30 Minutes of Initiation of Clevidipine
timeFrame: Within 30 minutes of study drug initiation
Secondary outcomes:
measure: Percentage of Participants Achieving a SBP of ≤160 mmHg Within 30 Minutes of Initiation of Clevidipine
timeFrame: Within 30 minutes of study drug initiation
measure: Percent Change From Baseline in Systolic Blood Pressure During the Initial 30 Minutes of Clevidipine Infusion
timeFrame: Baseline through 30 minutes post initiation of clevidipine infusion
measure: Magnitude, Frequency and Duration of Systolic Blood Pressure Excursions (Calculated as Area Under the Curve [AUC]) Outside the Target Range Normalized Per Hour for the Duration of the Clevidipine Monotherapy Infusion
timeFrame: Duration of the study drug infusion (up to 96 hours)
measure: Percent Time Blood Pressures Were Maintained Within the Target Range (Systolic Blood Pressure ≤160 mmHg to ≥140 mmHg) Over Each 24 Hour Period During Monotherapy Infusion of Clevidipine
timeFrame: From study drug initiation through termination (up to 96 h)
measure: Mean Dose of Clevidipine During the Treatment Period
timeFrame: Up to 96 hours
measure: Median Dose of Clevidipine During the Treatment Period
timeFrame: Up to 96 hours
measure: Proportion of Patients Requiring an Additional or Alternative Antihypertensive Agent(s) With or Without Clevidipine
timeFrame: Up to 96 hours
measure: Percent Change in Heart Rate During 30 of Initiation of Clevidipine
timeFrame: From study drug initiation through each specified timepoint
measure: The Percentage of Patients Whose Systolic Blood Pressure is <90 mmHg Within 30 Minutes of the Initiation of Clevidipine Infusion
timeFrame: Within 30 minutes of the initiation of study drug infusion
Other outcomes:
Locations:
city: Washington
country: United States
facility: Washington Hospital Center
state: District of Columbia
city: Honolulu
country: United States
facility: The Queens Medical Center
state: Hawaii
city: Baltimore
country: United States
facility: The John Hopkins Hospital
state: Maryland
city: Portland
country: United States
facility: Maine Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Greensboro
country: United States
facility: Guilford Neurologic - Moses H Cone Health System
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Hospitals
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University Stroke Research
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: San Antonio
country: United States
facility: The University Health Science Center at S.A.
state: Texas
city: Murray
country: United States
facility: Intermountain Medical Center
state: Utah
city: Liebigstraße 22a
country: Germany
facility: Universitätsklinikum Leipzig
state: Leipzig
city: Erlangen
country: Germany
facility: Universitatsklinikum Erlangen
city: Heidelberg
country: Germany
facility: Universitatsklinikum Heidelberg
Study officials:
affiliation: Duke University
name: Carmelo Graffagnino, MD
role: PRINCIPAL_INVESTIGATOR
References: