Clinical trial NCT00799604: Clevidipine Bolus Administration in the Treatment of Hypertensive Patients Undergoing Cardiac Surgery (SPRINT)
Official title: An Open-label Study in Patients Undergoing Cardiac Surgery to Evaluate the Effect of Bolus Clevidipine Administration (SPRINT)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertension
Keywords: Hypertension
Antihypertensive Agent
Calcium Channel Blocker
Lead sponsor: The Medicines Company
Sponsor class: INDUSTRY
First posted: 2008-12-01
Enrollment: 30
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: 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.

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 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

Primary outcomes:
measure: 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).
timeFrame: From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia).
measure: 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).
timeFrame: From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia).
Secondary outcomes:
measure: 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).
timeFrame: From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia).
measure: 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).
timeFrame: From start to 15 minutes of Bolus 1 of clevidipine (pre-anesthesia).
measure: 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).
timeFrame: From start to 15 minutes of Bolus 1 of clevidipine (pre-anesthesia).
measure: 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).
timeFrame: Up to 15 minutes following the first bolus dose of clevidipine (pre-anesthesia).
measure: Change in Heart Rate After Bolus 1 (Pre-anesthesia).
timeFrame: Baseline up until the first 15 minutes following Bolus 1 (pre-anesthesia).
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital, Harvard Medical School
state: Massachusetts
city: Philadelphia
country: United States
facility: Hospital of the University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Albert T. Cheung, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital
name: Edwin G. Avery, IV, MD
role: PRINCIPAL_INVESTIGATOR
References: