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

This study has been completed.
Sponsor:
Information provided by:
The Medicines Company
ClinicalTrials.gov Identifier:
NCT00799604
First received: November 26, 2008
Last updated: October 27, 2009
Last verified: October 2009
  Purpose

The purpose of this study is to evaluate the pharmacodynamics of a bolus dosing regimen of clevidipine 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 butyrate injectable emulsion
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 and percent change in systolic blood pressure from baseline within 15 minutes from the first bolus dose of clevidipine (pre-anesthesia). [ Time Frame: Within 15 minutes from the first bolus dose of clevidipine (pre-anesthesia). ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The percentage of patients with systolic blood pressure ≤85 mm Hg within 15 minutes from the first bolus dose of clevidipine (pre-anesthesia). [ Time Frame: Within 15 minutes from the first bolus dose of clevidipine (pre-anesthesia). ] [ Designated as safety issue: No ]
  • The median time to 5%, 10%, and 15% systolic blood pressure reduction from baseline within 15 minutes from the first bolus dose of clevidipine (pre-anesthesia). [ Time Frame: Within 15 minutes from the first bolus dose of clevidipine (pre-anesthesia). ] [ Designated as safety issue: No ]
  • The mean percent change in systolic blood pressure from baseline over time during the first 15 minutes following first bolus dose of clevidipine (pre-anesthesia). [ Time Frame: The first 15 minutes following first bolus dose of clevidipine (pre-anesthesia). ] [ Designated as safety issue: No ]
  • The median time to 50% and, when available, 90% recovery from maximum systolic blood pressure effect following the first bolus dose of clevidipine (pre-anesthesia). [ Time Frame: Following the first bolus dose of clevidipine (pre-anesthesia). ] [ Designated as safety issue: No ]
  • The area under the concentration versus time curve, maximum concentration, elimination half-life, clearance, volume of distribution, and elimination rate constant will be determined, if feasible, for each individual patient. [ Time Frame: Following the first bolus dose of clevidipine ] [ Designated as safety issue: No ]
  • The following pharmacodynamic parameters will be determined, if feasible, for each individual patient following the first bolus dose of clevidipine: area under the effect-time curve, maximum effect, and time to maximum observed effect. [ Time Frame: Following the first bolus dose of clevidipine. ] [ Designated as safety issue: No ]
  • The relationship between change in systolic blood pressure from baseline and the blood concentration of clevidipine following the first bolus dose. [ Time Frame: Following first bolus dose of clevidipine. ] [ Designated as safety issue: No ]
  • Incidence of adverse events and serious adverse events. [ Time Frame: Adverse events will be followed for 6 hours and serious adverse events for up to 24 hours after the final bolus dose. ] [ Designated as safety issue: Yes ]
  • Change in heart rate. [ Time Frame: Following the first bolus dose of clevidipine. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: November 2008
Primary Completion Date: October 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Clevidipine butyrate injectable emulsion
    Clevidipine (0.5mg/mL in 20% lipid emulsion) in 100mL bottles will be administered as an IV bolus (<5 sec) by rapid injection, directly into a peripheral venous catheter followed by a normal saline flush (10mL). 10 patients will be allocated to each of the following 3 planned dose cohorts: 250μg (0.5mL), 500μg (1mL), 125μg (0.25mL or 0.5mL of a 1:1 solution). Patients will be given a bolus dose of clevidipine prior to anesthesia; at the discretion of the investigator, a second bolus may be administered after induction of anesthesia and immediately prior to aortic cannulation at either 125μg, 250μg or 500μg based on earlier observed response to Bolus 1. An additional dose cohort of up to 10 patients may be added if required at a dose between 125μg and 500μg; final determination of dose will be based on the results of Cohorts 1-3. In Cohort 4, if required, the final determination of the dose to be used for Bolus 2 will be based on the results of Bolus 1 and Cohorts 1-3.
    Other Name: Cleviprex
Detailed Description:

This open-label, single-arm study is designed to demonstrate the efficacy and safety of a bolus dose of clevidipine, a vascular-selective L-type calcium channel antagonist, in the management of hypertension in patients undergoing cardiac surgery requiring the use of cardiopulmonary bypass.

Informed consent will be obtained from patients meeting the inclusion criteria before the initiation of any study-specific procedures. Prior to administration of study drug, a clinical examination will be carried out. For the purposes of this study, hypertension will be defined as systolic blood pressure ≥140 mm Hg immediately prior to initiation of study drug.

The study will occur in four separate periods: Screening period (-14 to -1 days), Treatment Period 1 (Day 1; before anesthesia to at least 15 minutes and up to 30 minutes after Bolus 1), Treatment Period 2 (Day 1; from the end of Treatment Period 1, after initiation of anesthesia to final bolus) and a Follow-up Period (up to 24 hours after final bolus), representing a maximum of 16 days on study.

It is planned that 10 patients will be allocated to each of the following 3 planned dose cohorts:

  • 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)

If the initial 5 patients dosed in a cohort demonstrate no response in SBP (≤5-10 mm Hg change in SBP) patients will be enrolled into the next higher dose cohort. If ≥1 of the initial patients in a cohort demonstrates a response in SBP, the full 10 patients will be enrolled. When at least 5 patients are enrolled in a cohort, dose escalation will be terminated if ≥60% of patients, demonstrate a SBP of ≤85 mm Hg (pre-anesthesia).

Clevidipine will be administered prior to induction of general anesthesia in Treatment Period 1 as an intravenous bolus (<5 seconds) by rapid injection directly into a peripheral venous catheter followed by a normal saline flush (10 mL). At the discretion of the Investigator, a second bolus dose of clevidipine (Bolus 2) may be administered in Treatment Period 2, after induction of general anesthesia at either 125 μg, 250 μg or 500 μg based upon the earlier observed response to Bolus 1.

An additional dose cohort of up to 10 patients may be added if required (Cohort 4) in which clevidipine will be administered at a dose between 125 μg and 500 μg. The final determination of the dose to be used in Cohort 4 will be based on the results of Cohorts 1, 2 and 3.

Assessment of safety will be performed throughout the treatment period and for at least 6 hours after termination of study drug. Patients will be followed for up to 24 hours after the 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
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: Linda Rootkin, Director of Clinical Operations, The Medicines Company
ClinicalTrials.gov Identifier: NCT00799604     History of Changes
Other Study ID Numbers: TMC-CLV-08-02
Study First Received: November 26, 2008
Last Updated: October 27, 2009
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 April 22, 2014