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

NCT00666328 | Completed Phase 3 Results

• 1 other identifier: TMC-CLV-07-02
• Study Type: interventional
• Target: 37
• Locations: 2 countries
• Sites: 17

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).

Conditions

Hypertension; Hemorrhage

Keywords

Hypertension; Hemorrhage; Intracranial Pressure; Antihypertensive Agent; Calcium Channel Blocker

Outcome Measures

Primary Outcomes (1)

• Median Time to Achieve Target SBP Range (≤160 mmHg to ≥140 mmHg) Within 30 Minutes of Initiation of Clevidipine

  The median time, in minutes, was estimated with its two-tailed 95% confidence interval from the time of the initiation of clevidipine infusion until the first observed SBP was achieved in the target range of ≤160 mmHg to ≥140 mmHg within the first 30 minutes of clevidipine treatment. If patients did not reach the blood pressure target range within the first 30 minutes, their data was considered censored at 30 minutes. If another IV and/or oral antihypertensive agent indicated for hypertension was administered less than 30 minutes prior to achieving the endpoint, the data was considered censored at the time when the additional or alternative antihypertensive agent was given.

  Within 30 minutes of study drug initiation

Secondary Outcomes (9)

• Percentage of Participants Achieving a SBP of ≤160 mmHg Within 30 Minutes of Initiation of Clevidipine

  Within 30 minutes of study drug initiation

• Percent Change From Baseline in Systolic Blood Pressure During the Initial 30 Minutes of Clevidipine Infusion

  Baseline through 30 minutes post initiation of clevidipine infusion

• 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

  Duration of the study drug infusion (up to 96 hours)

• 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

  From study drug initiation through termination (up to 96 h)

• Mean Dose of Clevidipine During the Treatment Period

  Up to 96 hours

Study Arms (1)

clevidipine

EXPERIMENTAL

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

Drug: clevidipine

Interventions

clevidipine 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.

Also known as: clevidipine injectable emulsion, clevidipine emulsion, Cleviprex

clevidipine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Medicines Company: lead

Study Sites (17)

Washington Hospital Center

Washington D.C., District of Columbia, 20010-2975, United States

Location

The Queens Medical Center

Honolulu, Hawaii, 96813, United States

Location

The John Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Maine Medical Center

Portland, Massachusetts, 04102, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Guilford Neurologic - Moses H Cone Health System

Greensboro, North Carolina, 27405, United States

Location

Cleveland Clinic Hospitals

Cleveland, Ohio, 44195, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Thomas Jefferson University Stroke Research

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

The University Health Science Center at S.A.

San Antonio, Texas, 78229-3900, United States

Location

Intermountain Medical Center

Murray, Utah, 84157, United States

Location

Universitätsklinikum Leipzig

Liebigstraße 22a, Leipzig, D-04103, Germany

Location

Universitatsklinikum Erlangen

Erlangen, D91054, Germany

Location

Universitatsklinikum Heidelberg

Heidelberg, D69120, Germany

Location

MeSH Terms

Conditions

Hypertension; Hemorrhage

Interventions

clevidipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Jason Campagna. MD, PhD
• Organization: The Medicines Company

jason.campagna@themedco.com

973-290-6199

Study Officials

• Carmelo Graffagnino, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2008
• First Posted: April 24, 2008
• Study Start: June 1, 2008
• Primary Completion: April 1, 2010
• Study Completion: April 1, 2010
• Last Updated: August 29, 2014
• Results First Posted: April 8, 2013

Record last verified: 2014-08

Locations

US (14); DE (3)