Trial Outcomes & Findings for Assessment of Efficacy, Safety and Dosing of Clevidipine in Pediatric Participants Undergoing Surgery (PIONEER) (NCT NCT01938547)

NCT ID: NCT01938547

Last Updated: 2025-04-17

Results Overview

Efficacy: Median time to attain the initial pre-specified target SBP range (≥20 mm Hg and ≤ 40 mm Hg apart). The reason for initiating clevidipine administration was to keep blood pressure within a pre-specified range during surgery. Time to first achieve SBP target range within first 30 minutes. A target systolic blood pressure (SBP) range was specified for each patient prior to study drug initiation and could not be changed for the first 30 minutes of the treatment period. Adolescent patients received an initial weight-based dose of 0.4 μg/kg/minute, to be maintained for the first 1.5 minutes. Treatment period: from study drug initiation to termination of infusion (up to 96 hours) was: Phase 1: initial dosing (0 to 1.5 minutes); Phase 2: titration and maintenance phase (\>1.5 minutes up to 96 hours); Phase 3: transition and termination phase where the study drug is ceased, and the patient is transitioned to an alternative IV or oral antihypertensive if required.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

22 participants

Primary outcome timeframe

During the first 30 minutes of clevidipine infusion start (baseline).

Results posted on

2025-04-17

Participant Flow

Participant milestones

Participant milestones
Measure
Clevidipine
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol. Following the initial dose, clevidipine was up-titrated every 1.5 minutes, according to participant need, to achieve a systolic blood pressure (SBP) within the pre-specified SBP target range. Doses could be increased by less than doubling, and the time between dose adjustments could be lengthened, as the target blood pressure was approached. The infusion rate may have been maintained for up to 96 hours, once the participant's SBP was within the target range, and titrated as necessary to maintain blood pressure within the range.
Overall Study
STARTED
22
Overall Study
COMPLETED
21
Overall Study
NOT COMPLETED
1

Reasons for withdrawal

Reasons for withdrawal
Measure
Clevidipine
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol. Following the initial dose, clevidipine was up-titrated every 1.5 minutes, according to participant need, to achieve a systolic blood pressure (SBP) within the pre-specified SBP target range. Doses could be increased by less than doubling, and the time between dose adjustments could be lengthened, as the target blood pressure was approached. The infusion rate may have been maintained for up to 96 hours, once the participant's SBP was within the target range, and titrated as necessary to maintain blood pressure within the range.
Overall Study
Physician Decision
1

Baseline Characteristics

Assessment of Efficacy, Safety and Dosing of Clevidipine in Pediatric Participants Undergoing Surgery (PIONEER)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol. Following the initial dose, clevidipine will be up-titrated every 1.5 minutes, according to participant need, to achieve a systolic blood pressure (SBP) within the pre-specified SBP target range. Doses may be increased by less than doubling, and the time between dose adjustments may be lengthened, as the target blood pressure is approached. The infusion rate may be maintained for up to 96 hours, once the participant's SBP is within the target range, and titrated as necessary to maintain blood pressure within the range.
Age, Categorical
<=18 years
21 Participants
n=99 Participants
Age, Categorical
Between 18 and 65 years
0 Participants
n=99 Participants
Age, Categorical
>=65 years
0 Participants
n=99 Participants
Age, Continuous
15.0 years
STANDARD_DEVIATION 1.56 • n=99 Participants
Sex: Female, Male
Female
17 Participants
n=99 Participants
Sex: Female, Male
Male
4 Participants
n=99 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
1 Participants
n=99 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
20 Participants
n=99 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=99 Participants
Race (NIH/OMB)
Asian
5 Participants
n=99 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=99 Participants
Race (NIH/OMB)
Black or African American
3 Participants
n=99 Participants
Race (NIH/OMB)
White
13 Participants
n=99 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=99 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=99 Participants
Region of Enrollment
United States
21 participants
n=99 Participants
Height
158.20 cm
STANDARD_DEVIATION 13.46 • n=99 Participants
Weight
51.49 kg
STANDARD_DEVIATION 13.47 • n=99 Participants
Baseline Blood Pressure
Systolic
111.0 mmHg
STANDARD_DEVIATION 17.67 • n=99 Participants
Baseline Blood Pressure
Diastolic
63.4 mmHg
STANDARD_DEVIATION 5.84 • n=99 Participants

PRIMARY outcome

Timeframe: During the first 30 minutes of clevidipine infusion start (baseline).

Population: Safety population: All patients who received any study drug.

Efficacy: Median time to attain the initial pre-specified target SBP range (≥20 mm Hg and ≤ 40 mm Hg apart). The reason for initiating clevidipine administration was to keep blood pressure within a pre-specified range during surgery. Time to first achieve SBP target range within first 30 minutes. A target systolic blood pressure (SBP) range was specified for each patient prior to study drug initiation and could not be changed for the first 30 minutes of the treatment period. Adolescent patients received an initial weight-based dose of 0.4 μg/kg/minute, to be maintained for the first 1.5 minutes. Treatment period: from study drug initiation to termination of infusion (up to 96 hours) was: Phase 1: initial dosing (0 to 1.5 minutes); Phase 2: titration and maintenance phase (\>1.5 minutes up to 96 hours); Phase 3: transition and termination phase where the study drug is ceased, and the patient is transitioned to an alternative IV or oral antihypertensive if required.

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Efficacy: Median Time to Attain the Initial Pre-specified Target SBP Range
7.9 minutes
Interval 7.2 to 10.5

PRIMARY outcome

Timeframe: During the first 30 minutes of clevidipine infusion start (baseline).

Population: Safety population: All patients who received any study drug. This was the primary population used for the safety analyses.

Efficacy: Number and percentage of participants achieving the initial pre-specified target SBP range within first 30 minutes of clevidipine infusion.

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Efficacy: Number and Percentage of Participants Achieving the Initial Pre-specified Target SBP Range -- During First 30 Min of Clevidipine Infusion
21 participants

PRIMARY outcome

Timeframe: During the first 30 minutes of clevidipine infusion start (baseline).

Population: Safety population: All patients who received any study drug. This was the primary population used for the safety analyses.

Efficacy: Total dose infused to attain the initial pre-specified target SBP range (≥20 mm Hg and ≤ 40 mm Hg apart) within the first 30 min.

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Efficacy: Total Dose to Attain the Initial Pre-specified Target SBP Range
0.28 mg
Interval 0.02 to 0.91

PRIMARY outcome

Timeframe: Duration of clevidipine infusion (minimum of 30 minutes up to a maximum 96 hours).

Population: Safety population: All patients who received any study drug. This was the primary population used for the safety analyses.

Pharmacodynamic (PD) variable: infusion rate. A target systolic blood pressure (SBP) range was specified for each patient prior to study drug initiation by the Investigator and could not be changed for the first 30 minutes of the treatment period. Adolescent patients received an initial weight-based dose of 0.4 μg/kg/minute, to be maintained for the first 1.5 minutes.

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Pharmacology: Pharmacodynamic Variable -- Infusion Rate
0.80 microgram/kg/min
Interval 0.4 to 3.2

PRIMARY outcome

Timeframe: From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours).

Population: PK/PD population: All patients who received any study drug, had at least one documented and evaluable blood concentration and/or SBP observation and documented dose records.

Pharmacology: Pharmacokinetic (PK) variables for clevidipine were established by non-compartmental analysis and non-linear mixed effects modelling (NONMEM). PK results represent those that were obtained during and after the infusion of clevidipine, started at infusion rate of 0.4 µg/kg/min and then titrated according to the study protocol. Tmax: The time it takes for a drug to reach the maximum concentration after administration of a drug.

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Pharmacology: Clevidipine -- Tmax
51 minutes
Standard Deviation 47

PRIMARY outcome

Timeframe: From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours).

Population: PK/PD population: All patients who received any study drug, had at least one documented and evaluable blood concentration and/or SBP observation and documented dose records.

Pharmacology: Pharmacokinetic (PK) variables for clevidipine were established by non-compartmental analysis and non-linear mixed effects modelling (NONMEM). PK results represent those that were obtained during and after the infusion of clevidipine, started at infusion rate of 0.4 µg/kg/min and then titrated according to the study protocol. Cmax: Highest concentration of a drug reached after administration.

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Pharmacology: Clevidipine -- Cmax
14.0 ng/mL
Standard Deviation 5.6

PRIMARY outcome

Timeframe: From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours).

Population: PK/PD population: All patients who received any study drug, had at least one documented and evaluable blood concentration and/or SBP observation and documented dose records.

Pharmacology: Pharmacokinetic (PK) variables for clevidipine were established by non-compartmental analysis and non-linear mixed effects modelling (NONMEM). PK results represent those that were obtained during and after the infusion of clevidipine, started at infusion rate of 0.4 µg/kg/min and then titrated according to the study protocol. AUC all: Area under the curve, represents the total drug exposure integrated over time.

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Pharmacology: Clevidipine -- Area Under the Concentration Curve (AUCall)
1598 min*ng/mL
Standard Deviation 1540

PRIMARY outcome

Timeframe: From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours).

Population: PK/PD population: All patients who received any study drug, had at least one documented and evaluable blood concentration and/or SBP observation and documented dose records.

Pharmacology: Pharmacokinetic (PK) variables for clevidipine were established by non-compartmental analysis and non-linear mixed effects modelling (NONMEM). PK results represent those that were obtained during and after the infusion of clevidipine, started at infusion rate of 0.4 µg/kg/min and then titrated according to the study protocol. AUC inf: Area under the curve of the blood concentration from time zero and extrapolated to infinity.

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Pharmacology: Clevidipine -- Area Under the Concentration Curve Infinity (AUCinf)
1598 min*ng/mL
Standard Deviation 1540

PRIMARY outcome

Timeframe: From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours).

Population: PK/PD population: All patients who received any study drug, had at least one documented and evaluable blood concentration and/or SBP observation and documented dose records.

Pharmacology: Pharmacokinetic (PK) variables for clevidipine were established by non-compartmental analysis and non-linear mixed effects modelling (NONMEM). PK results represent those that were obtained during and after the infusion of clevidipine, started at infusion rate of 0.4 µg/kg/min and then titrated according to the study protocol. Vd: Volume of distribution is defined as the total amount of drug in the body divided by its concentration in plasma.

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Pharmacology: Clevidipine -- Volume of Distribution (Vd)
789 mL/kg
Standard Deviation 1165

PRIMARY outcome

Timeframe: From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours).

Population: PK/PD population: All patients who received any study drug, had at least one documented and evaluable blood concentration and/or SBP observation and documented dose records.

Pharmacology: Pharmacokinetic (PK) variables for clevidipine were established by non-compartmental analysis and non-linear mixed effects modelling (NONMEM). PK results represent those that were obtained during and after the infusion of clevidipine, started at infusion rate of 0.4 µg/kg/min and then titrated according to the study protocol. CL: Total Clearance is defined as the rate at which a drug is removed from plasma (mg/min) divided by the concentration of that drug in the plasma (mg/mL).

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Pharmacology: Clevidipine -- Total Clearance (CL)
113 mL/min/kg
Standard Deviation 54

PRIMARY outcome

Timeframe: From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours).

Population: PK/PD population: All patients who received any study drug, had at least one documented and evaluable blood concentration and/or SBP observation and documented dose records.

Pharmacology: Pharmacokinetic (PK) variables for clevidipine were established by non-compartmental analysis and non-linear mixed effects modelling (NONMEM). PK results represent those that were obtained during and after the infusion of clevidipine, started at infusion rate of 0.4 µg/kg/min and then titrated according to the study protocol. T1/2: The half-life of a drug is the time it takes for the amount of a drug's active substance in your body to reduce by half.

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Pharmacology: Clevidipine -- Half-Life (T1/2)
4.3 min
Standard Deviation 3.6

SECONDARY outcome

Timeframe: From infusion start (baseline) to 30 minutes post baseline.

Population: Safety population: All patients who received any study drug.

Efficacy: Percent Change in SBP From Baseline at Each Time Point -- During First 30 Min of Infusion Start (Baseline).

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- During First 30 Min of Infusion Start (Baseline)
1.5 minutes
-0.6 percent change from baseline
Standard Deviation 9.53
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- During First 30 Min of Infusion Start (Baseline)
3.0 minutes
-3.4 percent change from baseline
Standard Deviation 8.19
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- During First 30 Min of Infusion Start (Baseline)
4.5 minutes
-4.7 percent change from baseline
Standard Deviation 6.68
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- During First 30 Min of Infusion Start (Baseline)
7.5 minutes
-11.6 percent change from baseline
Standard Deviation 7.18
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- During First 30 Min of Infusion Start (Baseline)
10.5 minutes
-18.3 percent change from baseline
Standard Deviation 6.89
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- During First 30 Min of Infusion Start (Baseline)
15 minutes
-18.2 percent change from baseline
Standard Deviation 8.09
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- During First 30 Min of Infusion Start (Baseline)
21 minutes
-18.6 percent change from baseline
Standard Deviation 8.28
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- During First 30 Min of Infusion Start (Baseline)
25.5 minutes
-19.3 percent change from baseline
Standard Deviation 9.18
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- During First 30 Min of Infusion Start (Baseline)
30 minutes
-20.8 percent change from baseline
Standard Deviation 7.62

SECONDARY outcome

Timeframe: At each hour from 30 minutes post-clevidipine infusion start (baseline) to 6 hours from baseline.

Population: Safety population: All patients who received any study drug.

Efficacy: Percent change from baseline (infusion start) in SBP at each hour after the first 30 minutes of clevidipine infusion up to the cessation of infusion (up to 6 hours from baseline).

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Efficacy: Percent Change From Baseline in SBP -- Hourly Measurements -- From 30 Min to 6 Hours of Infusion Start (Baseline)
1 hour
-22.9 percent change from baseline
Standard Deviation 9.47
Efficacy: Percent Change From Baseline in SBP -- Hourly Measurements -- From 30 Min to 6 Hours of Infusion Start (Baseline)
1.5 hours
-18.6 percent change from baseline
Standard Deviation 12.52
Efficacy: Percent Change From Baseline in SBP -- Hourly Measurements -- From 30 Min to 6 Hours of Infusion Start (Baseline)
3 hours
-15.3 percent change from baseline
Standard Deviation 6.47
Efficacy: Percent Change From Baseline in SBP -- Hourly Measurements -- From 30 Min to 6 Hours of Infusion Start (Baseline)
4 hours
-21.5 percent change from baseline
Standard Deviation 9.20
Efficacy: Percent Change From Baseline in SBP -- Hourly Measurements -- From 30 Min to 6 Hours of Infusion Start (Baseline)
5 hours
-21.4 percent change from baseline
Standard Deviation 14.07
Efficacy: Percent Change From Baseline in SBP -- Hourly Measurements -- From 30 Min to 6 Hours of Infusion Start (Baseline)
2 hours
-24.1 percent change from baseline
Standard Deviation 11.33
Efficacy: Percent Change From Baseline in SBP -- Hourly Measurements -- From 30 Min to 6 Hours of Infusion Start (Baseline)
6 hours
-14.29 percent change from baseline
Standard Deviation 0.0

SECONDARY outcome

Timeframe: During the first 12 hours (measured at each hour) after cessation of clevidipine infusion.

Population: Safety population: All patients who received any study drug.

Efficacy: Percent change in SBP from baseline at each time point -- from cessation of study drug infusion and up to 12 hours.

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- From Cessation of Study Drug Infusion up to 12 Hours
1 hour
-12.2 percent change from baseline
Standard Deviation 22.92
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- From Cessation of Study Drug Infusion up to 12 Hours
2 hours
-12.1 percent change from baseline
Standard Deviation 21.83
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- From Cessation of Study Drug Infusion up to 12 Hours
3 hours
-4.9 percent change from baseline
Standard Deviation 25.07
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- From Cessation of Study Drug Infusion up to 12 Hours
4 hours
-2.8 percent change from baseline
Standard Deviation 23.20
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- From Cessation of Study Drug Infusion up to 12 Hours
5 hours
-1.1 percent change from baseline
Standard Deviation 21.00
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- From Cessation of Study Drug Infusion up to 12 Hours
6 hours
0.5 percent change from baseline
Standard Deviation 21.76
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- From Cessation of Study Drug Infusion up to 12 Hours
7 hours
1.2 percent change from baseline
Standard Deviation 20.68
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- From Cessation of Study Drug Infusion up to 12 Hours
8 hours
-2.7 percent change from baseline
Standard Deviation 20.79
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- From Cessation of Study Drug Infusion up to 12 Hours
9 hours
1.7 percent change from baseline
Standard Deviation 24.21
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- From Cessation of Study Drug Infusion up to 12 Hours
10 hours
0.9 percent change from baseline
Standard Deviation 19.48
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- From Cessation of Study Drug Infusion up to 12 Hours
11 hours
-7.1 percent change from baseline
Standard Deviation 18.48
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- From Cessation of Study Drug Infusion up to 12 Hours
12 hours
-4.0 percent change from baseline
Standard Deviation 19.83

SECONDARY outcome

Timeframe: During the first 30 minutes and during the entire drug treatment period (up to a maximum of 96 hours of clevidipine infusion).

Population: Safety population: All patients who received any study drug.

Efficacy: Number and percentage of patients falling below the target systolic blood pressure range lower limit -- during the first 30 minutes and during the entire drug treatment period of clevidipine infusion.

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Efficacy: Number and Percentage of Patients Falling Below the Target Systolic Blood Pressure Range Lower Limit -- During the First 30 Minutes and During the Entire Drug Treatment Period of Clevidipine Infusion
First 30 minutes of clevidipine infusion
1 participants
Efficacy: Number and Percentage of Patients Falling Below the Target Systolic Blood Pressure Range Lower Limit -- During the First 30 Minutes and During the Entire Drug Treatment Period of Clevidipine Infusion
Up to 96 hours of clevidipine infusion
5 participants

SECONDARY outcome

Timeframe: From 30 minutes after infusion start (baseline) and up to 6 hours post-clevidipine infusion.

Population: Safety population: All patients who received any study drug.

The number and percentage of participants in whom the SBP was within target range at each hour after the first 30 minutes of clevidipine infusion (up to 6 hours).

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Efficacy: Number and Percentage of Participants in Whom the SBP Was Within Target Range at Each Hour After the First 30 Minutes of Clevidipine Infusion (up to 6 Hours)
SBP within target range at 1 hour
8 participants
Efficacy: Number and Percentage of Participants in Whom the SBP Was Within Target Range at Each Hour After the First 30 Minutes of Clevidipine Infusion (up to 6 Hours)
SBP within target range at 2 hour
5 participants
Efficacy: Number and Percentage of Participants in Whom the SBP Was Within Target Range at Each Hour After the First 30 Minutes of Clevidipine Infusion (up to 6 Hours)
SBP within target range at 3 hour
5 participants
Efficacy: Number and Percentage of Participants in Whom the SBP Was Within Target Range at Each Hour After the First 30 Minutes of Clevidipine Infusion (up to 6 Hours)
SBP within target range at 4 hour
1 participants
Efficacy: Number and Percentage of Participants in Whom the SBP Was Within Target Range at Each Hour After the First 30 Minutes of Clevidipine Infusion (up to 6 Hours)
SBP within target range at 5 hour
2 participants
Efficacy: Number and Percentage of Participants in Whom the SBP Was Within Target Range at Each Hour After the First 30 Minutes of Clevidipine Infusion (up to 6 Hours)
SBP within target range at 6 hour
0 participants

SECONDARY outcome

Timeframe: From infusion start (baseline) to 30 minutes post baseline.

Population: Safety population: All patients who received any study drug.

Efficacy: Percent change from baseline in heart rate (HR). From infusion start (baseline) to 30 minutes post baseline.

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
1.5 minutes
5.7 Percent change in HR from baseline
Standard Deviation 16.89
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
3 minutes
0.8 Percent change in HR from baseline
Standard Deviation 6.80
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
4.5 minutes
0.7 Percent change in HR from baseline
Standard Deviation 7.64
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
6 minutes
2.2 Percent change in HR from baseline
Standard Deviation 7.61
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
7.5 minutes
5.4 Percent change in HR from baseline
Standard Deviation 10.12
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
9 minutes
12.2 Percent change in HR from baseline
Standard Deviation 17.97
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
10.5 minutes
10.6 Percent change in HR from baseline
Standard Deviation 15.29
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
12 minutes
11.1 Percent change in HR from baseline
Standard Deviation 14.72
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
13.5 minutes
10.7 Percent change in HR from baseline
Standard Deviation 14.02
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
15 minutes
13.7 Percent change in HR from baseline
Standard Deviation 19.63
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
16.5 minutes
14.8 Percent change in HR from baseline
Standard Deviation 20.38
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
18 minutes
12.7 Percent change in HR from baseline
Standard Deviation 16.54
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
19.5 minutes
13.0 Percent change in HR from baseline
Standard Deviation 14.48
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
21 minutes
12.2 Percent change in HR from baseline
Standard Deviation 13.59
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
22.5 minutes
14.7 Percent change in HR from baseline
Standard Deviation 15.81
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
24.0 minutes
12.9 Percent change in HR from baseline
Standard Deviation 13.95
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
25.5 minutes
15.2 Percent change in HR from baseline
Standard Deviation 16.26
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
27 minutes
13.5 Percent change in HR from baseline
Standard Deviation 14.10
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
28.5 minutes
14.9 Percent change in HR from baseline
Standard Deviation 13.69
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
30 minutes
13.0 Percent change in HR from baseline
Standard Deviation 14.61

SECONDARY outcome

Timeframe: At each hour after 30 minutes post-clevidipine infusion start (baseline) and up to 6 hours.

Population: Safety population: All patients who received any study drug.

Efficacy: Percent change from baseline in heart rate (HR) -- From 30 Min to 6 Hours From Baseline.

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Efficacy: Percent Change From Baseline in Heart Rate (HR).
1 hour
11.5 Percent change in HR from baseline
Standard Deviation 16.13
Efficacy: Percent Change From Baseline in Heart Rate (HR).
2 hours
10.68 Percent change in HR from baseline
Standard Deviation 12.89
Efficacy: Percent Change From Baseline in Heart Rate (HR).
3 hours
8.5 Percent change in HR from baseline
Standard Deviation 17.64
Efficacy: Percent Change From Baseline in Heart Rate (HR).
4 hours
13.2 Percent change in HR from baseline
Standard Deviation 16.20
Efficacy: Percent Change From Baseline in Heart Rate (HR).
5 hours
11.3 Percent change in HR from baseline
Standard Deviation 12.26
Efficacy: Percent Change From Baseline in Heart Rate (HR).
6 hours
12.0 Percent change in HR from baseline
Standard Deviation 0.00

SECONDARY outcome

Timeframe: At each hour after cessation of clevidipine infusion (up to 12 hours).

Population: Safety population: All patients who received any study drug.

Efficacy: Percent change from baseline in heart rate. At each hour after cessation of clevidipine infusion (up to 12 hours).

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- From Cessation of Study Drug Infusion up to 12 Hours
1 hour
11.4 Percent change in HR from baseline
Standard Deviation 17.03
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- From Cessation of Study Drug Infusion up to 12 Hours
2 hours
13.2 Percent change in HR from baseline
Standard Deviation 17.88
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- From Cessation of Study Drug Infusion up to 12 Hours
3 hours
10.4 Percent change in HR from baseline
Standard Deviation 17.30
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- From Cessation of Study Drug Infusion up to 12 Hours
4 hours
17.0 Percent change in HR from baseline
Standard Deviation 29.48
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- From Cessation of Study Drug Infusion up to 12 Hours
5 hours
11.2 Percent change in HR from baseline
Standard Deviation 20.83
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- From Cessation of Study Drug Infusion up to 12 Hours
6 hours
12.3 Percent change in HR from baseline
Standard Deviation 23.55
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- From Cessation of Study Drug Infusion up to 12 Hours
7 hours
13.48 Percent change in HR from baseline
Standard Deviation 22.33
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- From Cessation of Study Drug Infusion up to 12 Hours
8 hours
12.0 Percent change in HR from baseline
Standard Deviation 22.71
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- From Cessation of Study Drug Infusion up to 12 Hours
9 hours
19.8 Percent change in HR from baseline
Standard Deviation 31.63
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- From Cessation of Study Drug Infusion up to 12 Hours
10 hours
16.8 Percent change in HR from baseline
Standard Deviation 24.90
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- From Cessation of Study Drug Infusion up to 12 Hours
11 hours
15.9 Percent change in HR from baseline
Standard Deviation 28.31
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- From Cessation of Study Drug Infusion up to 12 Hours
12 hours
13.0 Percent change in HR from baseline
Standard Deviation 21.54

SECONDARY outcome

Timeframe: Minimum of 30 minutes up to a maximum of 96 hours post infusion start (baseline).

Population: Safety population: All patients who received any study drug.

Efficacy: Number and percentage of participants who require rescue therapy (i.e. receive any alternative IV antihypertensive drug) at any time during the study drug treatment period.

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Efficacy: Number and Percentage of Participants Requiring Rescue Therapy
0 participants

SECONDARY outcome

Timeframe: Minimum of 30 minutes up to a maximum of 96 hours post infusion start (baseline).

Population: Safety population: All patients who received any study drug.

Number and percentage of participants discontinuing the study due to adverse events.

Outcome measures

Outcome measures
Measure
Clevidipine
n=21 Participants
An initial clevidipine IV infusion dose for the adolescent cohort has been specified per protocol.
Efficacy: Number and Percentage of Participants Discontinuing Due to Adverse Events
0 participants

Adverse Events

Clevidipine

Serious events: 1 serious events
Other events: 21 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Clevidipine
n=21 participants at risk
An initial clevidipine IV infusion dose for the adolescent cohort as specified per protocol.
Respiratory, thoracic and mediastinal disorders
Respiratory depression
4.8%
1/21 • Number of events 1 • From start of infusion (baseline) to 7 days after the end of clevidipine infusion (minimum of approximately 7.5 days up to a maximum of approximately 11.5 days).
Safety population was used for analysis of safety. Treatment-emergent adverse events (TEAEs) were defined as those adverse events (AEs) occurring after study drug initiation that were either not present at baseline or were present at baseline but increased in severity after study drug initiation.

Other adverse events

Other adverse events
Measure
Clevidipine
n=21 participants at risk
An initial clevidipine IV infusion dose for the adolescent cohort as specified per protocol.
Gastrointestinal disorders
Nausea
57.1%
12/21 • Number of events 12 • From start of infusion (baseline) to 7 days after the end of clevidipine infusion (minimum of approximately 7.5 days up to a maximum of approximately 11.5 days).
Safety population was used for analysis of safety. Treatment-emergent adverse events (TEAEs) were defined as those adverse events (AEs) occurring after study drug initiation that were either not present at baseline or were present at baseline but increased in severity after study drug initiation.
Gastrointestinal disorders
Constipation
47.6%
10/21 • Number of events 10 • From start of infusion (baseline) to 7 days after the end of clevidipine infusion (minimum of approximately 7.5 days up to a maximum of approximately 11.5 days).
Safety population was used for analysis of safety. Treatment-emergent adverse events (TEAEs) were defined as those adverse events (AEs) occurring after study drug initiation that were either not present at baseline or were present at baseline but increased in severity after study drug initiation.
Gastrointestinal disorders
Vomiting
42.9%
9/21 • Number of events 9 • From start of infusion (baseline) to 7 days after the end of clevidipine infusion (minimum of approximately 7.5 days up to a maximum of approximately 11.5 days).
Safety population was used for analysis of safety. Treatment-emergent adverse events (TEAEs) were defined as those adverse events (AEs) occurring after study drug initiation that were either not present at baseline or were present at baseline but increased in severity after study drug initiation.
Gastrointestinal disorders
Abdominal Pain
14.3%
3/21 • Number of events 3 • From start of infusion (baseline) to 7 days after the end of clevidipine infusion (minimum of approximately 7.5 days up to a maximum of approximately 11.5 days).
Safety population was used for analysis of safety. Treatment-emergent adverse events (TEAEs) were defined as those adverse events (AEs) occurring after study drug initiation that were either not present at baseline or were present at baseline but increased in severity after study drug initiation.
Nervous system disorders
Dizziness
33.3%
7/21 • Number of events 7 • From start of infusion (baseline) to 7 days after the end of clevidipine infusion (minimum of approximately 7.5 days up to a maximum of approximately 11.5 days).
Safety population was used for analysis of safety. Treatment-emergent adverse events (TEAEs) were defined as those adverse events (AEs) occurring after study drug initiation that were either not present at baseline or were present at baseline but increased in severity after study drug initiation.
Nervous system disorders
Headache
19.0%
4/21 • Number of events 4 • From start of infusion (baseline) to 7 days after the end of clevidipine infusion (minimum of approximately 7.5 days up to a maximum of approximately 11.5 days).
Safety population was used for analysis of safety. Treatment-emergent adverse events (TEAEs) were defined as those adverse events (AEs) occurring after study drug initiation that were either not present at baseline or were present at baseline but increased in severity after study drug initiation.
Nervous system disorders
Hypoaesthesia
9.5%
2/21 • Number of events 2 • From start of infusion (baseline) to 7 days after the end of clevidipine infusion (minimum of approximately 7.5 days up to a maximum of approximately 11.5 days).
Safety population was used for analysis of safety. Treatment-emergent adverse events (TEAEs) were defined as those adverse events (AEs) occurring after study drug initiation that were either not present at baseline or were present at baseline but increased in severity after study drug initiation.
Nervous system disorders
Sedation
9.5%
2/21 • Number of events 2 • From start of infusion (baseline) to 7 days after the end of clevidipine infusion (minimum of approximately 7.5 days up to a maximum of approximately 11.5 days).
Safety population was used for analysis of safety. Treatment-emergent adverse events (TEAEs) were defined as those adverse events (AEs) occurring after study drug initiation that were either not present at baseline or were present at baseline but increased in severity after study drug initiation.
General disorders
Pyrexia
23.8%
5/21 • Number of events 5 • From start of infusion (baseline) to 7 days after the end of clevidipine infusion (minimum of approximately 7.5 days up to a maximum of approximately 11.5 days).
Safety population was used for analysis of safety. Treatment-emergent adverse events (TEAEs) were defined as those adverse events (AEs) occurring after study drug initiation that were either not present at baseline or were present at baseline but increased in severity after study drug initiation.
General disorders
Fatigue
9.5%
2/21 • Number of events 2 • From start of infusion (baseline) to 7 days after the end of clevidipine infusion (minimum of approximately 7.5 days up to a maximum of approximately 11.5 days).
Safety population was used for analysis of safety. Treatment-emergent adverse events (TEAEs) were defined as those adverse events (AEs) occurring after study drug initiation that were either not present at baseline or were present at baseline but increased in severity after study drug initiation.
Musculoskeletal and connective tissue disorders
Muscle spasms
19.0%
4/21 • Number of events 4 • From start of infusion (baseline) to 7 days after the end of clevidipine infusion (minimum of approximately 7.5 days up to a maximum of approximately 11.5 days).
Safety population was used for analysis of safety. Treatment-emergent adverse events (TEAEs) were defined as those adverse events (AEs) occurring after study drug initiation that were either not present at baseline or were present at baseline but increased in severity after study drug initiation.
Blood and lymphatic system disorders
Anaemia
14.3%
3/21 • Number of events 3 • From start of infusion (baseline) to 7 days after the end of clevidipine infusion (minimum of approximately 7.5 days up to a maximum of approximately 11.5 days).
Safety population was used for analysis of safety. Treatment-emergent adverse events (TEAEs) were defined as those adverse events (AEs) occurring after study drug initiation that were either not present at baseline or were present at baseline but increased in severity after study drug initiation.

Additional Information

Clinical Trial Transparency

Chiesi Farmaceutici S.p.A.

Phone: + 39 0521 2791

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place