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

The Medicines Company

Status and phase: Completed; Phase 2

Conditions: Hypertension

Treatments: Drug: clevidipine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00799604

TMC-CLV-08-02

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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30 participants in 1 patient group

clevidipine

Experimental group

Description:

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)

Treatment:

Drug: clevidipine