Clevidipine Bolus Administration in the Treatment of Hypertensive Patients Undergoing Cardiac Surgery (SPRINT)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
The Medicines Company
ClinicalTrials.gov Identifier:
NCT00799604
First received: November 26, 2008
Last updated: May 12, 2014
Last verified: May 2014
  Purpose

This study was designed to evaluate the pharmacodynamics of a bolus dosing regimen of clevidipine, a vascular-selective L-type calcium channel antagonist, for the management of blood pressure in cardiac surgery patients, as well as to evaluate the efficacy, safety and pharmacokinetics of clevidipine after bolus administration.


Condition Intervention Phase
Hypertension
Drug: clevidipine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-label Study in Patients Undergoing Cardiac Surgery to Evaluate the Effect of Bolus Clevidipine Administration (SPRINT)

Resource links provided by NLM:


Further study details as provided by The Medicines Company:

Primary Outcome Measures:
  • The Mean Maximum Absolute Change in Systolic Blood Pressure From Baseline Within 15 Minutes From the First Bolus Dose of Clevidipine (Treatment Period 1, Bolus 1 - Pre-anesthesia). [ Time Frame: From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia). ] [ Designated as safety issue: No ]
    Blood Pressure was measured at 60, 45, 30, 0 seconds prior to first Bolus dose (Bolus 1), and every 5 seconds after Bolus 1 for 15 minutes. Baseline SBP of Bolus 1 is defined as, 'median of all measurements prior to or at the start of Bolus 1'. Locally weighted scatterplot smoothing (LOWESS) method was used to determine the minimum SBP value for each patient. Maximum absolute change is the minimum SBP value within 15 minutes from bolus 1 minus baseline value.

  • The Mean Maximum Percent Change in Systolic Blood Pressure From Baseline Within 15 Minutes From the First Bolus Dose of Clevidipine (Treatment Period 1, Bolus 1 - Pre-anesthesia). [ Time Frame: From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia). ] [ Designated as safety issue: No ]
    Blood Pressure was measured at 60, 45, 30, 0 seconds prior to first Bolus dose (Bolus 1), and every 5 seconds after Bolus 1 for 15 minutes. Baseline SBP of Bolus 1 is defined as, 'median of all measurements prior to or at the start of Bolus 1'. Locally weighted scatterplot smoothing (LOWESS) method was used to determine the minimum SBP value for each patient. Maximum percent change is defined as the maximum absolute change divided by the baseline value of bolus 1 and multiplied by 100.


Secondary Outcome Measures:
  • The Percentage of Patients With Systolic Blood Pressure ≤85 mm Hg Within 15 Minutes From the First Bolus Dose of Clevidipine (Treatment Period 1, Bolus 1 - Pre-anesthesia). [ Time Frame: From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia). ] [ Designated as safety issue: No ]
    The percentage is calculated using the number of patients with a systolic blood pressure ≤85 mm Hg within 15 minutes from the initial Bolus 1 dose divided by the total number of patients who were treated with a Bolus 1 clevidipine, and multiplied by 100.

  • The Median Time to 5%, 10%, and 15% Systolic Blood Pressure Reduction From Baseline Within 15 Minutes From the First Bolus Dose of Clevidipine (Treatment Period 1, Bolus 1 -Pre-anesthesia). [ Time Frame: From start to 15 minutes of Bolus 1 of clevidipine (pre-anesthesia). ] [ Designated as safety issue: No ]
    BP was measured at 60, 45, 30, 0 seconds prior to first Bolus dose (bolus 1), and every 5 seconds after Bolus 1 for 15 minutes. Baseline SBP of bolus 1 is defined as median of all measurements prior to or at the start of Bolus 1. The time at which first target SBP reduction (ex. 5%) from baseline was reached was identified for each patient using fitted values from LOWESS method. Kaplan-Meier method was used to estimate the median time. Patients who never reached 5%, 10% or 15% reduction, withdrew from study or changed antihypertensive within 15 minutes were censored.

  • The Mean Percent Change in Systolic Blood Pressure From Baseline Over Time During the First 15 Minutes Following First Bolus Dose of Clevidipine (Treatment Period 1, Bolus 1 - Pre-anesthesia). [ Time Frame: From start to 15 minutes of Bolus 1 of clevidipine (pre-anesthesia). ] [ Designated as safety issue: No ]
    BP was measured at 60, 45, 30, 0 seconds prior to first Bolus dose (Bolus 1), and every 5 seconds after Bolus 1 for 15 minutes. Baseline SBP of Bolus 1 is defined as median of all measurements prior to or at the start of Bolus 1. SBP change (percent change) from baseline is calculated at each collection time point after bolus 1 dose for each patient.

  • The Median Time to 50%, and, When Available, 90% Recovery From Maximum SBP Effect Following the First Bolus Dose of Clevidipine for Patients Who Achieved the Endpoints (Treatment Period 1, Bolus 1 - Pre-anesthesia). [ Time Frame: Up to 15 minutes following the first bolus dose of clevidipine (pre-anesthesia). ] [ Designated as safety issue: No ]
    Analysis is of the time in minutes between the recorded time at the maximum absolute change and the time of the systolic blood pressure value at the first 50% recovery. The 50% recovery value is equal to the minimum recorded systolic blood pressure value plus 50% of the maximum amount of systolic blood pressure reduction (the Bolus 1 baseline value minus the value at the maximum absolute change).

  • Change in Heart Rate After Bolus 1 (Pre-anesthesia). [ Time Frame: Baseline up until the first 15 minutes following Bolus 1 (pre-anesthesia). ] [ Designated as safety issue: No ]
    The baseline heart rate was measured as the median of all the heart rate measurements within 60 seconds or at the start of the administration of Bolus 1.


Enrollment: 30
Study Start Date: November 2008
Study Completion Date: October 2009
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: clevidipine

Patients were sequentially assigned to one of following three planned dose cohorts for Bolus 1 within the clevidipine arm:

  • Cohort 1: clevidipine 250 µg (0.5 mL)
  • Cohort 2: clevidipine 500 µg (1 mL)
  • Cohort 3: clevidipine 125 µg (0.25 mL or 0.5 mL of a 1:1 solution)
Drug: clevidipine
Clevidipine (0.5mg/mL in 20% lipid emulsion) was administered as an IV bolus (<5 sec) by rapid injection for Bolus 1 and for Bolus 2, if second bolus dose was administered, directly into a peripheral venous catheter followed by a normal saline flush (10mL).
Other Names:
  • clevidipine injectable emulsion
  • clevidipine emulsion
  • Cleviprex

Detailed Description:

Study participants were screened up to 14 days prior to their elective cardiac surgery. For the purpose of this study, hypertension was defined as systolic blood pressure (SBP) ≥140 mm Hg immediately prior to initiation of study drug.

On the day of surgery, an IV bolus dose of clevidipine (Bolus 1 - pre-anesthesia) was administered to each eligible study participant during Treatment Period 1 to decrease BP before induction of general anesthesia. The dose (either 125 μg, 250 μg or 500 μg) given was based on the assigned cohort for each participant, listed in the 'Arms' section below.

At the discretion of the investigator, a second IV bolus dose of clevidipine (Bolus 2 - with anesthesia) could have been administered during Treatment Period 2 at either 125 μg, 250 μg or 500 μg, based upon the earlier observed response to Bolus 1. This dose was administered after the induction of anesthesia, to decrease BP prior to cannulation of the ascending aorta for initiation of cardiopulmonary bypass.

Assessment of safety was performed throughout Treatment Periods 1 and 2 with Adverse Events (AEs) followed 6 hours post final bolus dose and Serious Adverse Events (SAEs) followed 24 hours post final bolus dose.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Require elective cardiac operation involving the use of cardiopulmonary bypass
  • Age 18 years or older
  • A history or hypertension and/or expected to require perioperative antihypertensive therapy in the opinion of the investigator
  • Written informed consent
  • Pre-anesthesia baseline SBP ≥140 mm Hg just prior to bolus, measured using an arterial line

Exclusion Criteria:

  • Receiving either intravenous vasopressor or intravenous vasodilatory therapy in the 72 hours prior to dosing
  • Critical left main coronary artery stenosis
  • Critical aortic valve (<0.5 cm3) or mitral valve (<1.0 cm3) stenosis
  • Acute myocardial infarction within the prior 14 days
  • Fully paced cardiac rhythm
  • Known or suspected aortic dissection
  • Requiring preoperative intra-aortic balloon pump counterpulsation therapy
  • Contraindication to transesophageal echocardiography
  • Positive pregnancy test or breast feeding
  • Intolerance or allergy to calcium channel blockers
  • Allergy to soybean oil or egg lecithin
  • Any condition(s) that in the Investigator's opinion would warrant exclusion from the study or prevent the patient from completing the study
  • Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of enrollment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00799604

Locations
United States, Massachusetts
Massachusetts General Hospital, Harvard Medical School
Boston, Massachusetts, United States, 02114
United States, Pennsylvania
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
The Medicines Company
Investigators
Principal Investigator: Albert T. Cheung, MD University of Pennsylvania
Principal Investigator: Edwin G. Avery, IV, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT00799604     History of Changes
Other Study ID Numbers: TMC-CLV-08-02
Study First Received: November 26, 2008
Results First Received: July 30, 2012
Last Updated: May 12, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by The Medicines Company:
Hypertension
Antihypertensive Agent
Calcium Channel Blocker

Additional relevant MeSH terms:
Hypertension
Vascular Diseases
Cardiovascular Diseases
Antihypertensive Agents
Calcium Channel Blockers
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014