Trial Outcomes & Findings for Clevidipine Bolus Administration in the Treatment of Hypertensive Patients Undergoing Cardiac Surgery (SPRINT) (NCT NCT00799604)

Last Updated: 2014-08-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

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

Results posted on

2014-08-29

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Planned Cohort 1: Clevidipine 250 μg (0.5 mL) Clevidipine was administered at 250 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (\<5 seconds) (Bolus 1 - pre-anesthesia) by rapid injection. At the discretion of the investigator, a second bolus (Bolus 2 - with anesthesia) could be administered during Treatment Period 2 after induction of general anesthesia at 125 μg, 250 μg or 500 μg based upon the earlier observed response to Bolus 1. Five participants who received a Bolus 1 dose of 250 μg during Treatment Period 1 and one participant who received a Bolus 1 dose of 125 μg during Treatment Period 1 received a Bolus 2 dose of 250 μg during Treatment Period 2 in this cohort.	Planned Cohort 2: Clevidipine 500 μg (1.0 mL) Clevidipine was administered at 500 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (\<5 seconds) (Bolus 1 - pre-anesthesia) by rapid injection. At the discretion of the investigator, a second bolus (Bolus 2 - with anesthesia) could be administered during Treatment Period 2 after induction of general anesthesia at 125 μg, 250 μg or 500 μg based upon the earlier observed response to Bolus 1. Six participants who received a Bolus 1 dose of 500 μg and six participants who received a Bolus 1 dose of 125 μg during Treatment Period 1 received a Bolus 2 dose of 500 μg during Treatment Period 2 in this cohort.	Planned Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5mL Sol) Clevidipine was administered at 125 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (\<5 seconds) (Bolus 1 - pre-anesthesia) by rapid injection. At the discretion of the investigator, a second bolus (Bolus 2 - with anesthesia) could be administered during Treatment Period 2 after induction of general anesthesia at 125 μg, 250 μg or 500 μg based upon the earlier observed response to Bolus 1. Three participants who received a Bolus 1 dose of 250 μg during Treatment Period 1 received a Bolus 2 dose of 125 μg during Treatment Period 2 in this cohort.
Bolus 1 (Pre-anesthesia) STARTED	10	10	10
Bolus 1 (Pre-anesthesia) COMPLETED	10	10	10
Bolus 1 (Pre-anesthesia) NOT COMPLETED	0	0	0
Bolus 2 (With Anesthesia) STARTED	6	12	3
Bolus 2 (With Anesthesia) COMPLETED	6	12	3
Bolus 2 (With Anesthesia) NOT COMPLETED	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: Clevidipine 250 μg (0.5 mL) n=10 Participants 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).	Cohort 2: Clevidipine 500 μg (1.0 mL) n=10 Participants 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).	Cohort 3: Clevidipine 125 μg ( mL) n=10 Participants 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).	Total n=30 Participants Total of all reporting groups
Age, Continuous	60.5 years STANDARD_DEVIATION 11.88 • n=5 Participants	66.4 years STANDARD_DEVIATION 8.62 • n=7 Participants	60.2 years STANDARD_DEVIATION 8.85 • n=5 Participants	62.4 years STANDARD_DEVIATION 9.98 • n=4 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	7 Participants n=7 Participants	9 Participants n=5 Participants	24 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants 0 • n=5 Participants	0 Participants 0 • n=7 Participants	0 Participants 0 • n=5 Participants	0 Participants 0 • n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	10 Participants 100.0 • n=5 Participants	10 Participants 100.0 • n=7 Participants	10 Participants 100.0 • n=5 Participants	30 Participants 100.0 • n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants 0 • n=5 Participants	0 Participants 0 • n=7 Participants	0 Participants 0 • n=5 Participants	0 Participants 0 • n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants	30 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment United States	10 participants n=5 Participants	10 participants n=7 Participants	10 participants n=5 Participants	30 participants n=4 Participants
Height	174.96 centimeters (cm) STANDARD_DEVIATION 10.381 • n=5 Participants	168.15 centimeters (cm) STANDARD_DEVIATION 11.462 • n=7 Participants	176.35 centimeters (cm) STANDARD_DEVIATION 9.663 • n=5 Participants	173.15 centimeters (cm) STANDARD_DEVIATION 10.792 • n=4 Participants
Weight	81.65 kilograms (kg) STANDARD_DEVIATION 15.374 • n=5 Participants	79.24 kilograms (kg) STANDARD_DEVIATION 12.639 • n=7 Participants	105.05 kilograms (kg) STANDARD_DEVIATION 24.724 • n=5 Participants	88.65 kilograms (kg) STANDARD_DEVIATION 21.279 • n=4 Participants
Screening Blood Pressure Systolic Blood Pressure (SBP)	159.0 mm Hg STANDARD_DEVIATION 17.45 • n=5 Participants	170.2 mm Hg STANDARD_DEVIATION 16.33 • n=7 Participants	175.5 mm Hg STANDARD_DEVIATION 19.43 • n=5 Participants	168.2 mm Hg STANDARD_DEVIATION 18.53 • n=4 Participants
Screening Blood Pressure Diastolic Blood Pressure (DBP)	80.0 mm Hg STANDARD_DEVIATION 8.71 • n=5 Participants	74.1 mm Hg STANDARD_DEVIATION 10.29 • n=7 Participants	77.7 mm Hg STANDARD_DEVIATION 11.51 • n=5 Participants	77.3 mm Hg STANDARD_DEVIATION 10.18 • n=4 Participants
Screening Heart Rate	73.1 Beats Per Minute (BPM) STANDARD_DEVIATION 18.69 • n=5 Participants	68.5 Beats Per Minute (BPM) STANDARD_DEVIATION 10.42 • n=7 Participants	69.3 Beats Per Minute (BPM) STANDARD_DEVIATION 10.49 • n=5 Participants	70.3 Beats Per Minute (BPM) STANDARD_DEVIATION 13.43 • n=4 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Clevidipine 250 μg (0.5 mL) n=10 Participants Clevidipine was administered at 250 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).	Cohort 2: Clevidipine 500 μg (1.0 mL) n=10 Participants Clevidipine was administered at 500 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).	Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) n=10 Participants Clevidipine was administered at 125 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).
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	-37.0 mm Hg Standard Deviation 17.76	-15.8 mm Hg Standard Deviation 11.43

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Clevidipine 250 μg (0.5 mL) n=10 Participants Clevidipine was administered at 250 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).	Cohort 2: Clevidipine 500 μg (1.0 mL) n=10 Participants Clevidipine was administered at 500 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).	Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) n=10 Participants Clevidipine was administered at 125 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).
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	-22.10 percent change Standard Deviation 9.288	-8.91 percent change Standard Deviation 5.966

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Cohort 1: Clevidipine 250 μg (0.5 mL) n=10 Participants Clevidipine was administered at 250 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).	Cohort 2: Clevidipine 500 μg (1.0 mL) n=10 Participants Clevidipine was administered at 500 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).	Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) n=10 Participants Clevidipine was administered at 125 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).
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 Interval 0.0 to 0.0	0 percent patients Interval 0.0 to 0.0	0 percent patients Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Clevidipine 250 μg (0.5 mL) n=10 Participants Clevidipine was administered at 250 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).	Cohort 2: Clevidipine 500 μg (1.0 mL) n=10 Participants Clevidipine was administered at 500 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).	Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) n=10 Participants Clevidipine was administered at 125 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).
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 Interval 0.8 to 1.4	0.8 minutes Interval 0.2 to 1.3	1.0 minutes Interval 0.7 to Not Estimable: Unable to be determined due to a lack of enough participants achieving a 5% systolic blood pressure reduction within 15 minutes within this cohort.
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 Interval 1.0 to Not Estimable: Unable to be determined due to a lack of enough participants achieving a 10% systolic blood pressure reduction within 15 minutes within this cohort.	1.1 minutes Interval 0.4 to 1.3	NA minutes Not Estimable: Unable to be determined due to a lack of enough participants achieving a 10% systolic blood pressure reduction within 15 minutes within this cohort.
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 Not Estimable: Unable to be determined due to a lack of enough participants achieving a 15% systolic blood pressure reduction within 15 minutes within this cohort.	1.2 minutes Interval 0.8 to Not Estimable: Unable to be determined due to a lack of enough participants achieving a 15% systolic blood pressure reduction within 15 minutes within this cohort.	NA minutes Not Estimable: Unable to be determined due to a lack of enough participants achieving a 15% systolic blood pressure reduction within 15 minutes within this cohort.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Cohort 1: Clevidipine 250 μg (0.5 mL) n=10 Participants Clevidipine was administered at 250 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).	Cohort 2: Clevidipine 500 μg (1.0 mL) n=10 Participants Clevidipine was administered at 500 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).	Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) n=10 Participants Clevidipine was administered at 125 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).
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	-0.10 percent change Standard Deviation 7.585	0.18 percent change Standard Deviation 3.034
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	-2.41 percent change Standard Deviation 6.057	-1.59 percent change Standard Deviation 3.172
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	-9.09 percent change Standard Deviation 6.901	-5.87 percent change Standard Deviation 3.705
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	-12.29 percent change Standard Deviation 8.714	-5.67 percent change Standard Deviation 5.848
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	-19.40 percent change Standard Deviation 8.744	-6.68 percent change Standard Deviation 3.694
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	-20.36 percent change Standard Deviation 10.773	-7.07 percent change Standard Deviation 5.336
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	-17.95 percent change Standard Deviation 9.732	-6.79 percent change Standard Deviation 5.665
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	-11.08 percent change Standard Deviation 5.711	-3.07 percent change Standard Deviation 4.170
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	-6.77 percent change Standard Deviation 7.837	-3.17 percent change Standard Deviation 3.443
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	-0.33 percent change Standard Deviation 14.384	-2.32 percent change Standard Deviation 3.347

SECONDARY outcome

Timeframe: 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).

Outcome measures

Outcome measures
Measure	Cohort 1: Clevidipine 250 μg (0.5 mL) n=10 Participants Clevidipine was administered at 250 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).	Cohort 2: Clevidipine 500 μg (1.0 mL) n=10 Participants Clevidipine was administered at 500 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).	Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) n=10 Participants Clevidipine was administered at 125 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).
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 Interval 0.4 to 3.9	2.9 minutes Interval 1.8 to 4.4	2.5 minutes Interval 1.1 to Not Estimable: Not reached since \>50% of patients did not achieve 50% of recovery within 15 min.
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 Interval 2.1 to Not Estimable: Not reached since \>50% of patients did not achieve 90% of recovery within 15 min.	6.8 minutes Interval 3.1 to Not Estimable: Not reached since \>50% of patients did not achieve 90% of recovery within 15 min.	NA minutes Not Estimable: Not reached since \>50% of patients did not achieve 90% of recovery within 15 min.

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Cohort 1: Clevidipine 250 μg (0.5 mL) n=10 Participants Clevidipine was administered at 250 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).	Cohort 2: Clevidipine 500 μg (1.0 mL) n=10 Participants Clevidipine was administered at 500 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).	Cohort 3: Clevidipine 125 μg (0.25 mL or 0.5 mL of a 1:1 Sol) n=10 Participants Clevidipine was administered at 125 μg during Treatment Period 1 prior to induction of general anesthesia as an IV bolus (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds).
Change in Heart Rate After Bolus 1 (Pre-anesthesia).	11.0 beats per minute (bpm) Standard Deviation 10.15	3.1 beats per minute (bpm) Standard Deviation 2.73	2.0 beats per minute (bpm) Standard Deviation 2.83

Adverse Events

All Participants Across All Cohorts and Treatment Periods

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	All Participants Across All Cohorts and Treatment Periods n=30 participants at risk Study participants were sequentially assigned one of three cohorts to receive either a 250 μg, 500 μg or 125 μg bolus dose of clevidipine during Treatment Period 1 prior to induction of general anesthesia (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds). At the discretion of the investigator, a second bolus could be administered during Treatment Period 2 after induction of general anesthesia (Bolus 2 - with anesthesia) at 125 μg, 250 μg or 500 μg based upon the earlier observed response to Bolus 1.
Nervous system disorders Encephalopathy	3.3% 1/30 • Number of events 1 • Non-serious AE(s) were documented and assessed following initiation of clevidipine administration through 6 hours post final bolus dose. SAEs were assessed up to 24 hours post final bolus dose, regardless of causal relationship to the study drug.

Other adverse events

Other adverse events
Measure	All Participants Across All Cohorts and Treatment Periods n=30 participants at risk Study participants were sequentially assigned one of three cohorts to receive either a 250 μg, 500 μg or 125 μg bolus dose of clevidipine during Treatment Period 1 prior to induction of general anesthesia (Bolus 1 - pre-anesthesia) by rapid injection (\<5 seconds). At the discretion of the investigator, a second bolus could be administered during Treatment Period 2 after induction of general anesthesia (Bolus 2 - with anesthesia) at 125 μg, 250 μg or 500 μg based upon the earlier observed response to Bolus 1.
Metabolism and nutrition disorders Acidosis	13.3% 4/30 • Non-serious AE(s) were documented and assessed following initiation of clevidipine administration through 6 hours post final bolus dose. SAEs were assessed up to 24 hours post final bolus dose, regardless of causal relationship to the study drug.
Respiratory, thoracic and mediastinal disorders Atelectasis	13.3% 4/30 • Non-serious AE(s) were documented and assessed following initiation of clevidipine administration through 6 hours post final bolus dose. SAEs were assessed up to 24 hours post final bolus dose, regardless of causal relationship to the study drug.
Vascular disorders Hypotension	13.3% 4/30 • Non-serious AE(s) were documented and assessed following initiation of clevidipine administration through 6 hours post final bolus dose. SAEs were assessed up to 24 hours post final bolus dose, regardless of causal relationship to the study drug.

Additional Information

Jason Campagna. MD, PhD

The Medicines Company

Phone: 973-290-6199

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The site agrees that publication of Study results at the site is not permitted until after the presentation and publication of the multi-center results or an affirmative decision is made by Sponsor not to proceed with such publication. In such a case, Sponsor shall provide access to all Study site data to the academic Study Coordination Center, or upon request Sponsor will provide access to all Study site data to Institution. The site will adhere to terms for Sponsor review prior to submission.
Publication restrictions are in place

Restriction type: OTHER