Hypertension
Conditions
Keywords
Hypertension, Antihypertensive Agent, Calcium Channel Blocker
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.
Interventions
DRUGclevidipine
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).
Sponsors
The Medicines Company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). | From start to 15 minutes of Bolus 1 dose of clevidipine (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. |
| 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). | From start to 15 minutes of Bolus 1 dose of clevidipine (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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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). | 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 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 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. |
| Change in Heart Rate After Bolus 1 (Pre-anesthesia). | Baseline up until the first 15 minutes following Bolus 1 (pre-anesthesia). | 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. |
| 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). | 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). |
| 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). | 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. |
Countries
United States
Participant flow
Recruitment details
Thirty patients were enrolled at two hospitals. All received an initial dose of clevidipine (Bolus 1-pre-anesthesia) during Treatment Period 1; 21 participants received a second bolus dose (Bolus 2-with anesthesia)during Treatment 2 per the discretion of the investigator at 250, 500 or 125μg, depending on patient response to Bolus 1.
Pre-assignment details
A screening period began up to 14 days prior to study drug administration, consisting of obtaining informed consent, confirming patient eligibility, and collecting screening assessments. Patient eligibility was further verified on treatment day to confirm SPB ≥140 mm Hg prior to study drug. If SBP was \<140 mm Hg, no study drug was administered.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Clevidipine 250 μg (0.5 mL) Baseline characteristics are reflective of the participant groupings during Treatment Period 1 (10 participants per cohort) during which clevidipine was administered at 250 μg prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds). | 10 |
| Cohort 2: Clevidipine 500 μg (1.0 mL) Baseline characteristics are reflective of the participant groupings during Treatment Period 1 (10 participants per cohort) during which Clevidipine was administered at 250 μg prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds). | 10 |
| Cohort 3: Clevidipine 125 μg ( mL) Baseline characteristics are reflective of the participant groupings during Treatment Period 1 (10 participants per cohort) during which clevidipine was administered at 250 μg prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds). | 10 |
| Total | 30 |
Baseline characteristics
| Characteristic | Total | Cohort 3: Clevidipine 125 μg ( mL) | Cohort 2: Clevidipine 500 μg (1.0 mL) | Cohort 1: Clevidipine 250 μg (0.5 mL) |
|---|---|---|---|---|
| Age, Continuous | 62.4 years STANDARD_DEVIATION 9.98 | 60.2 years STANDARD_DEVIATION 8.85 | 66.4 years STANDARD_DEVIATION 8.62 | 60.5 years STANDARD_DEVIATION 11.88 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants 0 | 0 Participants 0 | 0 Participants 0 | 0 Participants 0 |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants 100 | 10 Participants 100 | 10 Participants 100 | 10 Participants 100 |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants 0 | 0 Participants 0 | 0 Participants 0 | 0 Participants 0 |
| Height | 173.15 centimeters (cm) STANDARD_DEVIATION 10.792 | 176.35 centimeters (cm) STANDARD_DEVIATION 9.663 | 168.15 centimeters (cm) STANDARD_DEVIATION 11.462 | 174.96 centimeters (cm) STANDARD_DEVIATION 10.381 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 10 Participants | 10 Participants | 10 Participants |
| Region of Enrollment United States | 30 participants | 10 participants | 10 participants | 10 participants |
| Screening Blood Pressure Diastolic Blood Pressure (DBP) | 77.3 mm Hg STANDARD_DEVIATION 10.18 | 77.7 mm Hg STANDARD_DEVIATION 11.51 | 74.1 mm Hg STANDARD_DEVIATION 10.29 | 80.0 mm Hg STANDARD_DEVIATION 8.71 |
| Screening Blood Pressure Systolic Blood Pressure (SBP) | 168.2 mm Hg STANDARD_DEVIATION 18.53 | 175.5 mm Hg STANDARD_DEVIATION 19.43 | 170.2 mm Hg STANDARD_DEVIATION 16.33 | 159.0 mm Hg STANDARD_DEVIATION 17.45 |
| Screening Heart Rate | 70.3 Beats Per Minute (BPM) STANDARD_DEVIATION 13.43 | 69.3 Beats Per Minute (BPM) STANDARD_DEVIATION 10.49 | 68.5 Beats Per Minute (BPM) STANDARD_DEVIATION 10.42 | 73.1 Beats Per Minute (BPM) STANDARD_DEVIATION 18.69 |
| Sex: Female, Male Female | 6 Participants | 1 Participants | 3 Participants | 2 Participants |
| Sex: Female, Male Male | 24 Participants | 9 Participants | 7 Participants | 8 Participants |
| Weight | 88.65 kilograms (kg) STANDARD_DEVIATION 21.279 | 105.05 kilograms (kg) STANDARD_DEVIATION 24.724 | 79.24 kilograms (kg) STANDARD_DEVIATION 12.639 | 81.65 kilograms (kg) STANDARD_DEVIATION 15.374 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 12 / 30 |
| serious Total, serious adverse events | 1 / 30 |
Outcome results
Primary
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.
Time frame: From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia).
Population: Modified Intent-to-Treat (mITT) population: all enrolled patients who were deemed eligible for the study by meeting all inclusion and no exclusion criteria and were treated with clevidipine. The mITT population is the primary population for the analyses of efficacy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Clevidipine 250 μg (0.5 mL) | 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). | -18.8 mm Hg | Standard Deviation 6.51 |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | 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). | -37.0 mm Hg | Standard Deviation 17.76 |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | 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). | -15.8 mm Hg | Standard Deviation 11.43 |
Primary
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.
Time frame: From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia).
Population: Modified Intent-to-Treat (mITT) population: all enrolled patients who were deemed eligible for the study by meeting all inclusion and no exclusion criteria and were treated with clevidipine. The mITT population is the primary population for the analyses of efficacy.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Clevidipine 250 μg (0.5 mL) | 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). | -11.89 percent change | Standard Deviation 3.851 |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | 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). | -22.10 percent change | Standard Deviation 9.288 |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | 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). | -8.91 percent change | Standard Deviation 5.966 |
Secondary
Change in Heart Rate After Bolus 1 (Pre-anesthesia).
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.
Time frame: Baseline up until the first 15 minutes following Bolus 1 (pre-anesthesia).
Population: Safety population: all enrolled patients (irrespective of eligibility) who are dosed with clevidipine. The safety population will be the primary population used for the safety analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort 1: Clevidipine 250 μg (0.5 mL) | Change in Heart Rate After Bolus 1 (Pre-anesthesia). | 11.0 beats per minute (bpm) | Standard Deviation 10.15 |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | Change in Heart Rate After Bolus 1 (Pre-anesthesia). | 3.1 beats per minute (bpm) | Standard Deviation 2.73 |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | Change in Heart Rate After Bolus 1 (Pre-anesthesia). | 2.0 beats per minute (bpm) | Standard Deviation 2.83 |
Secondary
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).
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.
Time frame: From start to 15 minutes of Bolus 1 of clevidipine (pre-anesthesia).
Population: Modified Intent-to-Treat (mITT) population: all enrolled patients who are eligible for the study and treated with clevidipine. The mITT population will be the primary population for the analyses of efficacy.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Clevidipine 250 μg (0.5 mL) | 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). | SBP 3 minutes after Bolus 1 | -6.58 percent change | Standard Deviation 5.492 |
| Cohort 1: Clevidipine 250 μg (0.5 mL) | 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). | SBP 0.75 minutes after Bolus 1 | -5.22 percent change | Standard Deviation 4.916 |
| Cohort 1: Clevidipine 250 μg (0.5 mL) | 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). | SBP 15 minutes after Bolus 1 | 0.58 percent change | Standard Deviation 6.119 |
| Cohort 1: Clevidipine 250 μg (0.5 mL) | 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). | SBP 2 minutes after Bolus 1 | -9.51 percent change | Standard Deviation 4.669 |
| Cohort 1: Clevidipine 250 μg (0.5 mL) | 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). | SBP 1 minute after Bolus 1 | -8.37 percent change | Standard Deviation 4.181 |
| Cohort 1: Clevidipine 250 μg (0.5 mL) | 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). | SBP 0.25 minutes after Bolus 1 | 0.96 percent change | Standard Deviation 4.346 |
| Cohort 1: Clevidipine 250 μg (0.5 mL) | 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). | SBP 1.5 minutes after Bolus 1 | -8.64 percent change | Standard Deviation 3.031 |
| Cohort 1: Clevidipine 250 μg (0.5 mL) | 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). | SBP 7 minutes after Bolus 1 | -1.31 percent change | Standard Deviation 4.909 |
| Cohort 1: Clevidipine 250 μg (0.5 mL) | 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). | SBP 0.5 minutes after Bolus 1 | 2.79 percent change | Standard Deviation 5.397 |
| Cohort 1: Clevidipine 250 μg (0.5 mL) | 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). | SBP 5 minutes after Bolus 1 | -4.23 percent change | Standard Deviation 4.506 |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | 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). | SBP 1 minute after Bolus 1 | -12.29 percent change | Standard Deviation 8.714 |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | 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). | SBP 1.5 minutes after Bolus 1 | -19.40 percent change | Standard Deviation 8.744 |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | 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). | SBP 2 minutes after Bolus 1 | -20.36 percent change | Standard Deviation 10.773 |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | 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). | SBP 3 minutes after Bolus 1 | -17.95 percent change | Standard Deviation 9.732 |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | 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). | SBP 0.25 minutes after Bolus 1 | -0.10 percent change | Standard Deviation 7.585 |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | 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). | SBP 0.5 minutes after Bolus 1 | -2.41 percent change | Standard Deviation 6.057 |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | 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). | SBP 0.75 minutes after Bolus 1 | -9.09 percent change | Standard Deviation 6.901 |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | 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). | SBP 5 minutes after Bolus 1 | -11.08 percent change | Standard Deviation 5.711 |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | 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). | SBP 7 minutes after Bolus 1 | -6.77 percent change | Standard Deviation 7.837 |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | 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). | SBP 15 minutes after Bolus 1 | -0.33 percent change | Standard Deviation 14.384 |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | 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). | SBP 0.5 minutes after Bolus 1 | -1.59 percent change | Standard Deviation 3.172 |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | 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). | SBP 3 minutes after Bolus 1 | -6.79 percent change | Standard Deviation 5.665 |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | 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). | SBP 1.5 minutes after Bolus 1 | -6.68 percent change | Standard Deviation 3.694 |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | 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). | SBP 5 minutes after Bolus 1 | -3.07 percent change | Standard Deviation 4.17 |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | 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). | SBP 0.25 minutes after Bolus 1 | 0.18 percent change | Standard Deviation 3.034 |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | 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). | SBP 15 minutes after Bolus 1 | -2.32 percent change | Standard Deviation 3.347 |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | 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). | SBP 7 minutes after Bolus 1 | -3.17 percent change | Standard Deviation 3.443 |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | 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). | SBP 1 minute after Bolus 1 | -5.67 percent change | Standard Deviation 5.848 |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | 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). | SBP 0.75 minutes after Bolus 1 | -5.87 percent change | Standard Deviation 3.705 |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | 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). | SBP 2 minutes after Bolus 1 | -7.07 percent change | Standard Deviation 5.336 |
Secondary
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).
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).
Time frame: Up to 15 minutes following the first bolus dose of clevidipine (pre-anesthesia).
Population: Modified Intent-to-Treat (mITT) population: all enrolled patients who are eligible for the study and treated with clevidipine. The mITT population will be the primary population for the analyses of efficacy.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: Clevidipine 250 μg (0.5 mL) | 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 to 90% recovery in SBP | 5.2 minutes |
| Cohort 1: Clevidipine 250 μg (0.5 mL) | 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 to 50% recovery in SBP | 1.8 minutes |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | 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 to 50% recovery in SBP | 2.9 minutes |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | 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 to 90% recovery in SBP | 6.8 minutes |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | 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 to 50% recovery in SBP | 2.5 minutes |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | 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 to 90% recovery in SBP | NA minutes |
Secondary
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).
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.
Time frame: From start to 15 minutes of Bolus 1 of clevidipine (pre-anesthesia).
Population: Modified Intent-to-Treat (mITT) population: all enrolled patients who are eligible for the study and treated with clevidipine. The mITT population will be the primary population for the analyses of efficacy.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: Clevidipine 250 μg (0.5 mL) | 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). | 5 % Reduction | 0.9 minutes |
| Cohort 1: Clevidipine 250 μg (0.5 mL) | 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). | 15% Reduction | NA minutes |
| Cohort 1: Clevidipine 250 μg (0.5 mL) | 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). | 10% Reduction | 1.3 minutes |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | 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). | 10% Reduction | 1.1 minutes |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | 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). | 15% Reduction | 1.2 minutes |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | 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). | 5 % Reduction | 0.8 minutes |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | 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). | 5 % Reduction | 1.0 minutes |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | 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). | 15% Reduction | NA minutes |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | 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). | 10% Reduction | NA minutes |
Secondary
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).
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.
Time frame: From start to 15 minutes of Bolus 1 dose of clevidipine (pre-anesthesia).
Population: Modified Intent-to-Treat (mITT) population: all enrolled patients who are eligible for the study and treated with clevidipine. The mITT population will be the primary population for the analyses of efficacy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Clevidipine 250 μg (0.5 mL) | 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). | 0 percent patients |
| Cohort 2: Clevidipine 500 μg (1.0 mL) | 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). | 0 percent patients |
| Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) | 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). | 0 percent patients |