Heart Failure, Hypertension
Conditions
Keywords
Hypertension, Antihypertensive Agent, Calcium Channel Blocker
Brief summary
The purpose of this study was to evaluate the efficacy and safety of intravenous (IV) clevidipine as compared with standard of care IV antihypertensive agents for blood pressure (BP) lowering in patients with acute heart failure and elevated BP.
Detailed description
This study was an open-label randomized efficacy and safety pilot trial in patients with acute heart failure (AHF) and hypertension (systolic blood pressure \[SBP\] ≥160 mm Hg) requiring parenteral antihypertensive therapy. Eligible patients were randomized to receive clevidipine or standard of care (SOC) intravenous antihypertensive treatment in an open-label manner in a ratio of 1:1. At the time of randomization, a patient-specific, prespecified SBP target range was determined and be recorded, prior to study drug treatment. Information on the dosing regimen, use of additional or alternative agents and transition to oral therapy if needed is detailed in the study 'ARM' and 'INTERVENTION' sections. A Data Safety Monitoring Board was utilized periodically throughout the study to monitor the safety of patients. Adverse events were assessed for 7 days post-study randomization or hospital discharge, whichever occured first. Serious adverse events (SAEs) were assessed for 30 days following study randomization. Subjects were contacted by telephone or in person up to 5 days after their 30-day time point to determine if any SAEs occurred following study drug treatment and to follow up on the Heath Economic assessments.
Interventions
DRUGClevidipine
Clevidipine was to be administered continuously as monotherapy during the first 30 minutes. Use of an alternative IV antihypertensive agent(s) was discouraged and was limited to where medically necessary to maintain patient safety. Patients who received an alternative antihypertensive agent along with the study drug were allowed to continue in the study. If transition to an oral antihypertensive agent was required, it was to be administered approximately 1 hour prior to the termination of clevidipine with study drug down-titrated or terminated in order to maintain the desired blood pressure level.
DRUGStandard of Care IV antihypertensive
SOC IV antihypertensive agent will be administered for a minimum of 30 min and, if medically warranted, may continue beyond 96 hours at the investigator's discretion. As with clevidipine, the SOC agent was to be administered continuously as monotherapy during the first 30 minutes. Use of an alternative agent(s) was discouraged and was limited to where medically necessary to maintain patient safety. Higher dose titration rates were required to be attempted prior to making the decision to switch to or add on an alternative antihypertensive agent(s). Patients who received an alternative antihypertensive agent with SOC were allowed to continue in the study. If transition to an oral antihypertensive agent was required, it was to be administered per institutional practice.
Sponsors
The Medicines Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older * Presentation consistent with acute heart failure and pulmonary congestion on physical examination as evidenced by rales * Baseline systolic blood pressure (immediately prior to initiation of study drug) of ≥160 mm Hg * Dyspnea score (sitting) of at least 5 on a 10 cm visual analog scale (VAS) * Required IV antihypertensive therapy to lower blood pressure * Written informed consent
Exclusion criteria
* Administration of an agent (IV or oral) for the treatment of elevated BP within the previous 2 hours of randomization. (Previous short-acting non-IV nitrates, continuous positive airway pressure (CPAP), and bi-level positive airway pressure (BiPAP) were permitted) * Chest pain and/or electrocardiogram with ST segment changes consistent with acute coronary syndrome * Known or suspected aortic dissection * Acute myocardial infarction within the prior 14 days * Dialysis-dependant renal failure * Requirement for immediate endotracheal intubation * Positive pregnancy test, known pregnancy or breast feeding female * Intolerance or allergy to calcium channel blockers * Allergy to soybean oil or egg lecithin * Known liver failure, cirrhosis or pancreatitis * Prior directives against advanced life support * Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to First Achieve Initial Prespecified SBP Target Range and 15% Reduction From Baseline Within First 30 Minutes | Initiation of study drug through the initial 30-minutes | Time to first achieve the initial pre-specified systolic blood pressure (SBP) target range and a 15% SBP reduction from baseline is the time in minutes between the initiation of study medication and the time the patient first achieved both components. Median time was estimated using Kaplan Meier method. 95% two-sided confidence interval of the median time is from 'Simon and Lee, 1982'. If patients did not reach both components within 30 minutes from the initial treatment with study medication, or another antihypertensive agent was administered, the patient was censored at 30 minutes or the time when another antihypertensive agent is given, whichever came first. |
| Percentage to First Achieve Initial Prespecified SBP Target Range [≥20 mm Hg and ≤40 mm Hg Apart] and 15% Reduction From Baseline Within First 30 Minutes | Initiation of study drug through the initial 30-minutes | Analysis of the percentage of patients achieving both components of this composite endpoint (attainment of the initial prespecified SBP target range and a 15% reduction in SBP from baseline) was calculated within each treatment group using the number of mITT patients achieving the SBP reduction goal divided by the number of mITT patients, and multiplied by 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Falling Below Lower Limit of SBP Target Range Within First 30 Minutes | Initiation of study drug through the initial 30-minutes | The percentage of patients in whom the SBP fell below the lower limit of the prespecified target range at any time during the first 30 minutes was calculated within each treatment group using the number of mITT patients achieving the endpoint divided by the number of mITT patients and multiplied by 100. Two-tailed 95% CIs were computed for these percentages. |
| Percentage Falling Below Lower Limit of SBP Target Range at Any Time During Study | Initiation through termination of study drug (up to 96 hours) | The percentage of patients in whom the SBP fell below the lower limit of the prespecified target range at any time during the entire study drug treatment period (up to 96 hours) was calculated within each treatment group using the number of mITT patients achieving the endpoint divided by the number of mITT patients and multiplied by 100. Two-tailed 95% CIs were computed for these percentages. |
| Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point | Baseline (immediately prior to study drug administration) through 1 hour after study drug termination | A validated visual analog scale (VAS) with a horizontal ruler showing increments from 0 to 100 mm with 0 = Best and 100 = Worst was used. The test was asked from the patient's perspective and had to be administered with patient sitting. Relative change in VAS from baseline is the value at each time point minus the baseline value. Relative change from baseline was summarized descriptively (with associated two-tailed 95% CIs of the mean values) at 15, 30 and 45 minutes and at 1, 2, 3 hours and 12 hours, and 1 hour post termination of study drug treatment. |
| Percentage Reaching Prespecified Target Range Without Falling Below Lower Limit of Target Range Within First 30 Minutes | Initiation of study drug through the initial 30-minutes | The percentage of patients reaching this endpoint was calculated within each treatment group using the number of mITT patients reaching the endpoint divided by the number of mITT patients, and multiplied by 100. Two-tailed 95% CIs were computed for these percentages. |
| Percentage of Patients Who Received Any Alternative IV Antihypertensive Drug at Any Time During Study Drug Treatment | Initiation through termination of study drug (up to 96 hours) | The percentage of patients who received any alternative IV antihypertensive drug at any time during the study drug treatment period (up to 96 hours) was calculated using mITT patients within each treatment group. |
| Percentage of Patients With at Least One Episode of SBP < 90 mm Hg During Study Drug Administration (up to 96 Hours) | Initiation through termination of study drug (up to 96 hours) | The percent of patients with at least one episode of SBP \<90 mm Hg was calculated as the number of mITT patients who had at least one episode of SBP\<90 mm Hg during study drug administration up to 96 hours divided by mITT patients, and multiplied by 100 for each treatment group. |
| Number of Patients That Require Intubation During Study Drug Administration up to 96 Hours | Initiation through termination of study drug (up to 96 hours) | The number of patients requiring intubation was calculated based on the total number of mITT patients. |
| Time to Use Other IV Antihypertensives During the Study Drug Administration | Initiation of study drug through any other concomitant IV antihypertensive agent administered, up to 96 hours | The length of time to use other IV antihypertensive agents was defined as the duration in hours from the initiation of study drug through the time when any other concomitant IV antihypertensive agent was administered, thus, representing the time period without use of any other concomitant IV antihypertensive agent. Median time to use other IV antihypertensive agents was obtained using Kaplan-Meier method. If a patient did not receive any concomitant IV antihypertensive during the 96-hour treatment period, this patient was considered censored at 96 hours. If study drug was stopped less than 96 hours and the patient has no concomitant IV antihypertensive agent, the patient was considered censored when study drug was stopped. |
| SBP Area Under the Curve (AUC) Outside Prespecified Target Range | Initiation of study drug through end of monotherapy (up to 96 hours) | The magnitude and duration of SBP excursions was calculated as the area under the curve (AUC) for each patient, using the trapezoidal rule, related to time (in minutes) that each patient's SBP was outside the target range. AUC was determined based on data collected from the initiation of study medication through the end of monotherapy treatment up to 96 hours, normalized per hour, and expressed as mmHg × minute/hour. |
Countries
France, Germany, United States
Participant flow
Recruitment details
Participants with symptoms of acute heart failure (AHF) and elevated blood pressure (BP) presented to the Emergency Departments at 13 hospitals (9 US; 3 France; 1 Germany) between Feb 2009 and Feb 2012 and received either clevidipine or standard of care (SOC) continuous IV antihypertensive therapy for management of their blood pressure.
Pre-assignment details
Eligible patients who met all inclusion and none of the exclusion criteria, including confirmation that systolic blood pressure (SBP) was ≥160 mm Hg immediately prior to study drug, were randomized into the study. If SBP \< 160 mm Hg immediately prior to drug, the patient was not to receive study drug and was treated per institutional practice.
Participants by arm
| Arm | Count |
|---|---|
| Clevidipine Emulsion All randomized and eligible patients who received any dose of clevidipine. | 51 |
| SOC IV Antihypertensive Therapy All randomized and eligible patients who received any SOC dose. | 53 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 2 |
| Overall Study | Lost to Follow-up | 2 | 3 |
| Overall Study | Withdrew Consent | 1 | 0 |
Baseline characteristics
| Characteristic | Clevidipine Emulsion | SOC IV Antihypertensive Therapy | Total |
|---|---|---|---|
| Age, Continuous | 61.8 years STANDARD_DEVIATION 14.95 | 60.2 years STANDARD_DEVIATION 14.89 | 61.0 years STANDARD_DEVIATION 14.87 |
| Diastolic Blood Pressure (DBP) | 102.2 mm Hg STANDARD_DEVIATION 24.14 | 99.2 mm Hg STANDARD_DEVIATION 24.28 | 100.7 mm Hg STANDARD_DEVIATION 24.14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants | 53 Participants | 103 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 39 Participants | 44 Participants | 83 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 9 Participants | 21 Participants |
| Sex: Female, Male Female | 25 Participants | 29 Participants | 54 Participants |
| Sex: Female, Male Male | 26 Participants | 24 Participants | 50 Participants |
| Systolic Blood Pressure (SBP) | 188.2 mm Hg STANDARD_DEVIATION 25.02 | 184.8 mm Hg STANDARD_DEVIATION 21.92 | 186.5 mm Hg STANDARD_DEVIATION 23.44 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 51 | 19 / 53 |
| serious Total, serious adverse events | 12 / 51 | 10 / 53 |
Outcome results
Primary
Percentage to First Achieve Initial Prespecified SBP Target Range [≥20 mm Hg and ≤40 mm Hg Apart] and 15% Reduction From Baseline Within First 30 Minutes
Analysis of the percentage of patients achieving both components of this composite endpoint (attainment of the initial prespecified SBP target range and a 15% reduction in SBP from baseline) was calculated within each treatment group using the number of mITT patients achieving the SBP reduction goal divided by the number of mITT patients, and multiplied by 100.
Time frame: Initiation of study drug through the initial 30-minutes
Population: mITT population: All randomized and eligible patients who were dosed with study drug and have a baseline SBP ≥160 mm Hg, at least one post-baseline on-treatment SBP measurement, and a confirmed diagnosis of AHF
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clevidipine | Percentage to First Achieve Initial Prespecified SBP Target Range [≥20 mm Hg and ≤40 mm Hg Apart] and 15% Reduction From Baseline Within First 30 Minutes | 70.5 Percentage of patients |
| Standard of Care | Percentage to First Achieve Initial Prespecified SBP Target Range [≥20 mm Hg and ≤40 mm Hg Apart] and 15% Reduction From Baseline Within First 30 Minutes | 36.6 Percentage of patients |
Primary
Time to First Achieve Initial Prespecified SBP Target Range and 15% Reduction From Baseline Within First 30 Minutes
Time to first achieve the initial pre-specified systolic blood pressure (SBP) target range and a 15% SBP reduction from baseline is the time in minutes between the initiation of study medication and the time the patient first achieved both components. Median time was estimated using Kaplan Meier method. 95% two-sided confidence interval of the median time is from 'Simon and Lee, 1982'. If patients did not reach both components within 30 minutes from the initial treatment with study medication, or another antihypertensive agent was administered, the patient was censored at 30 minutes or the time when another antihypertensive agent is given, whichever came first.
Time frame: Initiation of study drug through the initial 30-minutes
Population: mITT population: All randomized and eligible patients who were dosed with study drug and have a baseline SBP ≥160 mm Hg, at least one post-baseline on-treatment SBP measurement, and a confirmed diagnosis of AHF
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clevidipine | Time to First Achieve Initial Prespecified SBP Target Range and 15% Reduction From Baseline Within First 30 Minutes | 15.0 Minutes |
| Standard of Care | Time to First Achieve Initial Prespecified SBP Target Range and 15% Reduction From Baseline Within First 30 Minutes | NA Minutes |
Secondary
Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point
A validated visual analog scale (VAS) with a horizontal ruler showing increments from 0 to 100 mm with 0 = Best and 100 = Worst was used. The test was asked from the patient's perspective and had to be administered with patient sitting. Relative change in VAS from baseline is the value at each time point minus the baseline value. Relative change from baseline was summarized descriptively (with associated two-tailed 95% CIs of the mean values) at 15, 30 and 45 minutes and at 1, 2, 3 hours and 12 hours, and 1 hour post termination of study drug treatment.
Time frame: Baseline (immediately prior to study drug administration) through 1 hour after study drug termination
Population: mITT population: All randomized and eligible patients who were dosed with study drug and have a baseline SBP ≥160 mm Hg, at least one post-baseline on-treatment SBP measurement, and a confirmed diagnosis of AHF
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Clevidipine | Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point | Baseline Through Initial 15 Min- CLV n=44;SOC n=38 | -18.6 millimeters (mm) | Standard Deviation 17.49 |
| Clevidipine | Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point | Baseline Through Initial 30 Min- CLV n=43;SOC n=39 | -28.8 millimeters (mm) | Standard Deviation 19.94 |
| Clevidipine | Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point | Baseline Through Initial 45 Min- CLV n=43;SOC n=39 | -37.1 millimeters (mm) | Standard Deviation 20.87 |
| Clevidipine | Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point | Baseline Through Initial 1 H- CLV n=41;SOC n=38 | -43.6 millimeters (mm) | Standard Deviation 21.74 |
| Clevidipine | Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point | Baseline Through Initial 2 H- CLV n=29;SOC n=29 | -45.2 millimeters (mm) | Standard Deviation 22.66 |
| Clevidipine | Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point | Baseline Through Initial 3 H- CLV n=14;SOC n=22 | -47.9 millimeters (mm) | Standard Deviation 16.57 |
| Clevidipine | Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point | Baseline Through Initial 12 H- CLV n=0;SOC n=7 | NA millimeters (mm) | — |
| Clevidipine | Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point | Baseline Through 1 H Post Drug- CLV n=41;SOC n=33 | -50.1 millimeters (mm) | Standard Deviation 23.22 |
| Standard of Care | Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point | Baseline Through 1 H Post Drug- CLV n=41;SOC n=33 | -50.1 millimeters (mm) | Standard Deviation 26.09 |
| Standard of Care | Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point | Baseline Through Initial 15 Min- CLV n=44;SOC n=38 | -16.1 millimeters (mm) | Standard Deviation 19.78 |
| Standard of Care | Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point | Baseline Through Initial 2 H- CLV n=29;SOC n=29 | -35.3 millimeters (mm) | Standard Deviation 22.3 |
| Standard of Care | Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point | Baseline Through Initial 30 Min- CLV n=43;SOC n=39 | -22.8 millimeters (mm) | Standard Deviation 21.03 |
| Standard of Care | Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point | Baseline Through Initial 12 H- CLV n=0;SOC n=7 | -57.9 millimeters (mm) | Standard Deviation 15.18 |
| Standard of Care | Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point | Baseline Through Initial 45 Min- CLV n=43;SOC n=39 | -27.9 millimeters (mm) | Standard Deviation 21.73 |
| Standard of Care | Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point | Baseline Through Initial 3 H- CLV n=14;SOC n=22 | -40.5 millimeters (mm) | Standard Deviation 21.69 |
| Standard of Care | Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point | Baseline Through Initial 1 H- CLV n=41;SOC n=38 | -34.6 millimeters (mm) | Standard Deviation 23.38 |
Secondary
Number of Patients That Require Intubation During Study Drug Administration up to 96 Hours
The number of patients requiring intubation was calculated based on the total number of mITT patients.
Time frame: Initiation through termination of study drug (up to 96 hours)
Population: mITT population: All randomized and eligible patients who were dosed with study drug and have a baseline SBP ≥160 mm Hg, at least one post-baseline on-treatment SBP measurement, and a confirmed diagnosis of AHF
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clevidipine | Number of Patients That Require Intubation During Study Drug Administration up to 96 Hours | 0 Patients |
| Standard of Care | Number of Patients That Require Intubation During Study Drug Administration up to 96 Hours | 0 Patients |
Secondary
Percentage Falling Below Lower Limit of SBP Target Range at Any Time During Study
The percentage of patients in whom the SBP fell below the lower limit of the prespecified target range at any time during the entire study drug treatment period (up to 96 hours) was calculated within each treatment group using the number of mITT patients achieving the endpoint divided by the number of mITT patients and multiplied by 100. Two-tailed 95% CIs were computed for these percentages.
Time frame: Initiation through termination of study drug (up to 96 hours)
Population: mITT population: All randomized and eligible patients who were dosed with study drug and have a baseline SBP ≥160 mm Hg, at least one post-baseline on-treatment SBP measurement, and a confirmed diagnosis of AHF
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clevidipine | Percentage Falling Below Lower Limit of SBP Target Range at Any Time During Study | 68.2 Percentage of patients |
| Standard of Care | Percentage Falling Below Lower Limit of SBP Target Range at Any Time During Study | 70.7 Percentage of patients |
Secondary
Percentage Falling Below Lower Limit of SBP Target Range Within First 30 Minutes
The percentage of patients in whom the SBP fell below the lower limit of the prespecified target range at any time during the first 30 minutes was calculated within each treatment group using the number of mITT patients achieving the endpoint divided by the number of mITT patients and multiplied by 100. Two-tailed 95% CIs were computed for these percentages.
Time frame: Initiation of study drug through the initial 30-minutes
Population: mITT population: All randomized and eligible patients who were dosed with study drug and have a baseline SBP ≥160 mm Hg, at least one post-baseline on-treatment SBP measurement, and a confirmed diagnosis of AHF
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clevidipine | Percentage Falling Below Lower Limit of SBP Target Range Within First 30 Minutes | 34.1 Percentage of patients |
| Standard of Care | Percentage Falling Below Lower Limit of SBP Target Range Within First 30 Minutes | 2.4 Percentage of patients |
Secondary
Percentage of Patients Who Received Any Alternative IV Antihypertensive Drug at Any Time During Study Drug Treatment
The percentage of patients who received any alternative IV antihypertensive drug at any time during the study drug treatment period (up to 96 hours) was calculated using mITT patients within each treatment group.
Time frame: Initiation through termination of study drug (up to 96 hours)
Population: mITT population: All randomized and eligible patients who were dosed with study drug and have a baseline SBP ≥160 mm Hg, at least one post-baseline on-treatment SBP measurement, and a confirmed diagnosis of AHF
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clevidipine | Percentage of Patients Who Received Any Alternative IV Antihypertensive Drug at Any Time During Study Drug Treatment | 15.9 Percentage of patients |
| Standard of Care | Percentage of Patients Who Received Any Alternative IV Antihypertensive Drug at Any Time During Study Drug Treatment | 51.2 Percentage of patients |
Secondary
Percentage of Patients With at Least One Episode of SBP < 90 mm Hg During Study Drug Administration (up to 96 Hours)
The percent of patients with at least one episode of SBP \<90 mm Hg was calculated as the number of mITT patients who had at least one episode of SBP\<90 mm Hg during study drug administration up to 96 hours divided by mITT patients, and multiplied by 100 for each treatment group.
Time frame: Initiation through termination of study drug (up to 96 hours)
Population: Safety population: All randomized and eligible patients who were dosed with study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clevidipine | Percentage of Patients With at Least One Episode of SBP < 90 mm Hg During Study Drug Administration (up to 96 Hours) | 5.9 Percentage of patients |
| Standard of Care | Percentage of Patients With at Least One Episode of SBP < 90 mm Hg During Study Drug Administration (up to 96 Hours) | 1.9 Percentage of patients |
Secondary
Percentage Reaching Prespecified Target Range Without Falling Below Lower Limit of Target Range Within First 30 Minutes
The percentage of patients reaching this endpoint was calculated within each treatment group using the number of mITT patients reaching the endpoint divided by the number of mITT patients, and multiplied by 100. Two-tailed 95% CIs were computed for these percentages.
Time frame: Initiation of study drug through the initial 30-minutes
Population: mITT population: All randomized and eligible patients who were dosed with study drug and have a baseline SBP ≥160 mm Hg, at least one post-baseline on-treatment SBP measurement, and a confirmed diagnosis of AHF
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Clevidipine | Percentage Reaching Prespecified Target Range Without Falling Below Lower Limit of Target Range Within First 30 Minutes | 45.5 Percentage of patients |
| Standard of Care | Percentage Reaching Prespecified Target Range Without Falling Below Lower Limit of Target Range Within First 30 Minutes | 51.2 Percentage of patients |
Secondary
SBP Area Under the Curve (AUC) Outside Prespecified Target Range
The magnitude and duration of SBP excursions was calculated as the area under the curve (AUC) for each patient, using the trapezoidal rule, related to time (in minutes) that each patient's SBP was outside the target range. AUC was determined based on data collected from the initiation of study medication through the end of monotherapy treatment up to 96 hours, normalized per hour, and expressed as mmHg × minute/hour.
Time frame: Initiation of study drug through end of monotherapy (up to 96 hours)
Population: mITT population: All randomized and eligible patients who were dosed with study drug and have a baseline SBP ≥160 mm Hg, at least one post-baseline on-treatment SBP measurement, and a confirmed diagnosis of AHF
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Clevidipine | SBP Area Under the Curve (AUC) Outside Prespecified Target Range | 494.96 mm Hg x min/h | Standard Deviation 428.554 |
| Standard of Care | SBP Area Under the Curve (AUC) Outside Prespecified Target Range | 966.15 mm Hg x min/h | Standard Deviation 860.278 |
Secondary
Time to Use Other IV Antihypertensives During the Study Drug Administration
The length of time to use other IV antihypertensive agents was defined as the duration in hours from the initiation of study drug through the time when any other concomitant IV antihypertensive agent was administered, thus, representing the time period without use of any other concomitant IV antihypertensive agent. Median time to use other IV antihypertensive agents was obtained using Kaplan-Meier method. If a patient did not receive any concomitant IV antihypertensive during the 96-hour treatment period, this patient was considered censored at 96 hours. If study drug was stopped less than 96 hours and the patient has no concomitant IV antihypertensive agent, the patient was considered censored when study drug was stopped.
Time frame: Initiation of study drug through any other concomitant IV antihypertensive agent administered, up to 96 hours
Population: mITT population: All randomized and eligible patients who were dosed with study drug and have a baseline SBP ≥160 mm Hg, at least one post-baseline on-treatment SBP measurement, and a confirmed diagnosis of AHF
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Clevidipine | Time to Use Other IV Antihypertensives During the Study Drug Administration | NA Hours |
| Standard of Care | Time to Use Other IV Antihypertensives During the Study Drug Administration | 5.7 Hours |