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

NCT00799604 | Completed Phase 2 Results

• 1 other identifier: TMC-CLV-08-02
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Hypertension

Keywords

Hypertension; Antihypertensive Agent; Calcium Channel Blocker

Outcome Measures

Primary Outcomes (2)

• 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).

  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.

  From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia).

• 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).

  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.

  From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia).

Secondary Outcomes (5)

• 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).

  From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia).

• 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).

  From start to 15 minutes of Bolus 1 of clevidipine (pre-anesthesia).

• 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).

  From start to 15 minutes of Bolus 1 of clevidipine (pre-anesthesia).

• 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).

  Up to 15 minutes following the first bolus dose of clevidipine (pre-anesthesia).

• Change in Heart Rate After Bolus 1 (Pre-anesthesia).

  Baseline up until the first 15 minutes following Bolus 1 (pre-anesthesia).

Study Arms (1)

clevidipine

EXPERIMENTAL

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

Interventions

clevidipine DRUG

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).

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:

• 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

You may not qualify if:

• 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
• 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 (2)

Massachusetts General Hospital, Harvard Medical School

Boston, Massachusetts, 02114, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Hypertension

Interventions

clevidipine

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

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

jason.campagna@themedco.com

973-290-6199

Study Officials

• Albert T. Cheung, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• Edwin G. Avery, IV, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2008
• First Posted: December 1, 2008
• Study Start: November 1, 2008
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: August 29, 2014
• Results First Posted: June 4, 2014

Record last verified: 2014-08

Locations

US (2)