Pediatric Perioperative Blood Pressure Management
Conditions
Keywords
perioperative, blood pressure, pediatrics, pediatric surgery
Brief summary
Evaluate the efficacy, safety, and dosing of clevidipine as an intravenous (IV) infusion for blood pressure (BP) management in paediatric participants in the perioperative setting.
Detailed description
This was an open-label study to assess, in a stepwise approach across 4 age cohorts from oldest to youngest (birth to \<age 18), the efficacy and safety of clevidipine exposure for a minimum of 30 minutes and up to a maximum of 96 hours in pediatric participants undergoing a surgical procedure with anesthesia for greater than or equal to 1 hour and for whom parenteral IV infusion of antihypertensive therapy for the management of blood pressure was expected. The reason for initiating clevidipine administration was to keep blood pressure within a pre-specified range during surgery. After the study completion for Cohort 1 (adolescent patients 12 to less than 18 years), the PIONEER study was placed on partial clinical hold by the FDA; later, the study was terminated by the sponsor. Enrolment of the subsequent cohorts did not take place; results are presented for Cohort 1 only.
Interventions
DRUGclevidipine
Sponsors
Chiesi Farmaceutici S.p.A.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 17 Years
Healthy volunteers
No
Inclusion criteria
* Less than 18 years of age * Written informed consent obtained before initiation of any study-related procedures * The enrolling physician determines that the participant will likely require a 15% reduction in BP during the perioperative course * Intra-arterial line is available for blood pressure monitoring * Surgical procedure requiring a minimum of 1 hour of anesthesia, in which IV antihypertensive therapy to control BP for at least 30 minutes is anticipated
Exclusion criteria
* Administration of an IV or oral antihypertensive agent within 2 hours prior to study drug administration * Congenital heart disease described as single ventricle * Evidence of liver failure, severe liver disease, pulmonary disease (e.g. uncontrolled asthma), hyperlipidemia, lipoid nephrosis, lipid dysfunction or acute pancreatitis * Allergy to soya bean oil or egg lecithin * Known to be intolerant to calcium channel blockers * Hemophilia or blood coagulation disorders * Any serious medical condition which, in the opinion of the investigator, is likely to interfere with study procedures * Clinically significant abnormal physical findings at the screening evaluation * Any serious surgical or medical condition which, in the opinion of the investigator, is likely to interfere with study procedures or with the pharmacokinetics or pharmacodynamics of the study drug * Participant is terminally ill (death likely to occur within 48 hours) * Use of Methylphenidate, calcium channel blockers, Aripiprazole and other atypical anti- psychotics and antihypertensives used for BP control within 2 hours prior to study drug initiation * Positive serum or urine pregnancy test for any female of child bearing potential * Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of enrollment * Participants who, for any reason, are deemed by the Investigator to be inappropriate for this study * Participant is a relative of the Investigator or his/her deputy, research assistant, pharmacist, study coordinator, other staff directly involved in the conduct of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacology: Clevidipine -- Half-Life (T1/2) | From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours). | 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. |
| Efficacy: Total Dose to Attain the Initial Pre-specified Target SBP Range | During the first 30 minutes of clevidipine infusion start (baseline). | 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. |
| Efficacy: Median Time to Attain the Initial Pre-specified Target SBP Range | During the first 30 minutes of clevidipine infusion start (baseline). | 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. |
| Efficacy: Number and Percentage of Participants Achieving the Initial Pre-specified Target SBP Range -- During First 30 Min of Clevidipine Infusion | During the first 30 minutes of clevidipine infusion start (baseline). | Efficacy: Number and percentage of participants achieving the initial pre-specified target SBP range within first 30 minutes of clevidipine infusion. |
| Pharmacology: Pharmacodynamic Variable -- Infusion Rate | Duration of clevidipine infusion (minimum of 30 minutes up to a maximum 96 hours). | 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. |
| Pharmacology: Clevidipine -- Tmax | From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours). | 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. |
| Pharmacology: Clevidipine -- Cmax | From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours). | 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. |
| Pharmacology: Clevidipine -- Area Under the Concentration Curve (AUCall) | From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours). | 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. |
| Pharmacology: Clevidipine -- Area Under the Concentration Curve Infinity (AUCinf) | From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours). | 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. |
| Pharmacology: Clevidipine -- Volume of Distribution (Vd) | From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours). | 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. |
| Pharmacology: Clevidipine -- Total Clearance (CL) | From 30 minutes before start of infusion up to termination of infusion (minimum of 9 hours up to a maximum of 96 hours). | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy: Percent Change From Baseline in SBP -- Hourly Measurements -- From 30 Min to 6 Hours of Infusion Start (Baseline) | At each hour from 30 minutes post-clevidipine infusion start (baseline) to 6 hours from baseline. | 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). |
| Efficacy: Percent Change in SBP From Baseline at Each Time Point -- From Cessation of Study Drug Infusion up to 12 Hours | During the first 12 hours (measured at each hour) after cessation of clevidipine infusion. | Efficacy: Percent change in SBP from baseline at each time point -- from cessation of study drug infusion and up to 12 hours. |
| 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 | During the first 30 minutes and during the entire drug treatment period (up to a maximum of 96 hours of clevidipine infusion). | 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. |
| 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) | From 30 minutes after infusion start (baseline) and up to 6 hours post-clevidipine infusion. | 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). |
| Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion | From infusion start (baseline) to 30 minutes post baseline. | Efficacy: Percent change from baseline in heart rate (HR). From infusion start (baseline) to 30 minutes post baseline. |
| Efficacy: Percent Change From Baseline in Heart Rate (HR). | At each hour after 30 minutes post-clevidipine infusion start (baseline) and up to 6 hours. | Efficacy: Percent change from baseline in heart rate (HR) -- From 30 Min to 6 Hours From Baseline. |
| Efficacy: Percent Change From Baseline in Heart Rate (HR) -- From Cessation of Study Drug Infusion up to 12 Hours | At each hour after cessation of clevidipine infusion (up to 12 hours). | Efficacy: Percent change from baseline in heart rate. At each hour after cessation of clevidipine infusion (up to 12 hours). |
| Efficacy: Number and Percentage of Participants Requiring Rescue Therapy | Minimum of 30 minutes up to a maximum of 96 hours post infusion start (baseline). | 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. |
| Efficacy: Number and Percentage of Participants Discontinuing Due to Adverse Events | Minimum of 30 minutes up to a maximum of 96 hours post infusion start (baseline). | Number and percentage of participants discontinuing the study due to adverse events. |
| Efficacy: Percent Change in SBP From Baseline at Each Time Point -- During First 30 Min of Infusion Start (Baseline) | From infusion start (baseline) to 30 minutes post baseline. | Efficacy: Percent Change in SBP From Baseline at Each Time Point -- During First 30 Min of Infusion Start (Baseline). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Clevidipine 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. | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Clevidipine |
|---|---|
| Age, Categorical <=18 years | 21 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 15.0 years STANDARD_DEVIATION 1.56 |
| Baseline Blood Pressure Diastolic | 63.4 mmHg STANDARD_DEVIATION 5.84 |
| Baseline Blood Pressure Systolic | 111.0 mmHg STANDARD_DEVIATION 17.67 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 158.20 cm STANDARD_DEVIATION 13.46 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 13 Participants |
| Region of Enrollment United States | 21 participants |
| Sex: Female, Male Female | 17 Participants |
| Sex: Female, Male Male | 4 Participants |
| Weight | 51.49 kg STANDARD_DEVIATION 13.47 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 21 |
| other Total, other adverse events | 21 / 21 |
| serious Total, serious adverse events | 1 / 21 |
Outcome results
Primary
Efficacy: Median Time to Attain the Initial Pre-specified Target SBP Range
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.
Time frame: During the first 30 minutes of clevidipine infusion start (baseline).
Population: Safety population: All patients who received any study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clevidipine | Efficacy: Median Time to Attain the Initial Pre-specified Target SBP Range | 7.9 minutes |
Primary
Efficacy: Number and Percentage of Participants Achieving the Initial Pre-specified Target SBP Range -- During First 30 Min of Clevidipine Infusion
Efficacy: Number and percentage of participants achieving the initial pre-specified target SBP range within first 30 minutes of clevidipine infusion.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clevidipine | Efficacy: Number and Percentage of Participants Achieving the Initial Pre-specified Target SBP Range -- During First 30 Min of Clevidipine Infusion | 21 participants |
Primary
Efficacy: Total Dose to Attain the Initial Pre-specified Target SBP Range
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clevidipine | Efficacy: Total Dose to Attain the Initial Pre-specified Target SBP Range | 0.28 mg |
Primary
Pharmacology: Clevidipine -- Area Under the Concentration Curve (AUCall)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clevidipine | Pharmacology: Clevidipine -- Area Under the Concentration Curve (AUCall) | 1598 min*ng/mL | Standard Deviation 1540 |
Primary
Pharmacology: Clevidipine -- Area Under the Concentration Curve Infinity (AUCinf)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clevidipine | Pharmacology: Clevidipine -- Area Under the Concentration Curve Infinity (AUCinf) | 1598 min*ng/mL | Standard Deviation 1540 |
Primary
Pharmacology: Clevidipine -- Cmax
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clevidipine | Pharmacology: Clevidipine -- Cmax | 14.0 ng/mL | Standard Deviation 5.6 |
Primary
Pharmacology: Clevidipine -- Half-Life (T1/2)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clevidipine | Pharmacology: Clevidipine -- Half-Life (T1/2) | 4.3 min | Standard Deviation 3.6 |
Primary
Pharmacology: Clevidipine -- Tmax
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clevidipine | Pharmacology: Clevidipine -- Tmax | 51 minutes | Standard Deviation 47 |
Primary
Pharmacology: Clevidipine -- Total Clearance (CL)
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).
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clevidipine | Pharmacology: Clevidipine -- Total Clearance (CL) | 113 mL/min/kg | Standard Deviation 54 |
Primary
Pharmacology: Clevidipine -- Volume of Distribution (Vd)
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clevidipine | Pharmacology: Clevidipine -- Volume of Distribution (Vd) | 789 mL/kg | Standard Deviation 1165 |
Primary
Pharmacology: Pharmacodynamic Variable -- Infusion Rate
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.
Time frame: 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.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clevidipine | Pharmacology: Pharmacodynamic Variable -- Infusion Rate | 0.80 microgram/kg/min |
Secondary
Efficacy: Number and Percentage of Participants Discontinuing Due to Adverse Events
Number and percentage of participants discontinuing the study due to adverse events.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clevidipine | Efficacy: Number and Percentage of Participants Discontinuing Due to Adverse Events | 0 participants |
Secondary
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)
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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
Efficacy: Number and Percentage of Participants Requiring Rescue Therapy
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.
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clevidipine | Efficacy: Number and Percentage of Participants Requiring Rescue Therapy | 0 participants |
Secondary
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
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Clevidipine | 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 |
| Clevidipine | 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
Efficacy: Percent Change From Baseline in Heart Rate (HR).
Efficacy: Percent change from baseline in heart rate (HR) -- From 30 Min to 6 Hours From Baseline.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Clevidipine | Efficacy: Percent Change From Baseline in Heart Rate (HR). | 1 hour | 11.5 Percent change in HR from baseline | Standard Deviation 16.13 |
| Clevidipine | Efficacy: Percent Change From Baseline in Heart Rate (HR). | 2 hours | 10.68 Percent change in HR from baseline | Standard Deviation 12.89 |
| Clevidipine | Efficacy: Percent Change From Baseline in Heart Rate (HR). | 3 hours | 8.5 Percent change in HR from baseline | Standard Deviation 17.64 |
| Clevidipine | Efficacy: Percent Change From Baseline in Heart Rate (HR). | 4 hours | 13.2 Percent change in HR from baseline | Standard Deviation 16.2 |
| Clevidipine | Efficacy: Percent Change From Baseline in Heart Rate (HR). | 5 hours | 11.3 Percent change in HR from baseline | Standard Deviation 12.26 |
| Clevidipine | Efficacy: Percent Change From Baseline in Heart Rate (HR). | 6 hours | 12.0 Percent change in HR from baseline | Standard Deviation 0 |
Secondary
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- During First 30 Min of Infusion
Efficacy: Percent change from baseline in heart rate (HR). From infusion start (baseline) to 30 minutes post baseline.
Time frame: From infusion start (baseline) to 30 minutes post baseline.
Population: Safety population: All patients who received any study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Clevidipine | 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 |
| Clevidipine | 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 6.8 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 14.1 |
| Clevidipine | 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 |
| Clevidipine | 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
Efficacy: Percent Change From Baseline in Heart Rate (HR) -- From Cessation of Study Drug Infusion up to 12 Hours
Efficacy: Percent change from baseline in heart rate. At each hour after cessation of clevidipine infusion (up to 12 hours).
Time frame: At each hour after cessation of clevidipine infusion (up to 12 hours).
Population: Safety population: All patients who received any study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 17.3 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 24.9 |
| Clevidipine | 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 |
| Clevidipine | 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
Efficacy: Percent Change From Baseline in SBP -- Hourly Measurements -- From 30 Min to 6 Hours of Infusion Start (Baseline)
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).
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 9.2 |
| Clevidipine | 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 |
| Clevidipine | 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 |
Secondary
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- During First 30 Min of Infusion Start (Baseline)
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- During First 30 Min of Infusion Start (Baseline).
Time frame: From infusion start (baseline) to 30 minutes post baseline.
Population: Safety population: All patients who received any study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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
Efficacy: Percent Change in SBP From Baseline at Each Time Point -- From Cessation of Study Drug Infusion up to 12 Hours
Efficacy: Percent change in SBP from baseline at each time point -- from cessation of study drug infusion and up to 12 hours.
Time frame: During the first 12 hours (measured at each hour) after cessation of clevidipine infusion.
Population: Safety population: All patients who received any study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 23.2 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |
| Clevidipine | 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 |