Trial Outcomes & Findings for Clevidipine in the Treatment of Blood Pressure in Patients With Acute Heart Failure (PRONTO) (NCT NCT00803634)

Last Updated: 2014-08-29

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

117 participants

Primary outcome timeframe

Initiation of study drug through the initial 30-minutes

Results posted on

2014-08-29

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	Clevidipine Clevidipine (0.5 mg/mL in 20% lipid emulsion) was administered intravenously via a single dedicated line to all patients randomized to the clevidipine arm. Clevidipine was titrated to effect thereafter by doubling the dose every 3 minutes, per physician discretion and as tolerated by the patient, until the desired SBP target range was attained. The infusion rate could then be increased or decreased as needed in order to maintain blood pressure for minimum of 30 minutes and a maximum duration of 96 hours. The minimum infusion rate was 1 mg/h and maximum infusion rate was 32 mg/h.	Standard of Care The selection of the standard of care (SOC) IV antihypertensive treatment agent was at the discretion of the investigator. The infusion was administered per the institution's treatment practice. Dose titrations were to be performed to the maximum allowed or tolerated dose in order to achieve SBP control within the patient-specified SBP target range within the first 30 minutes. SOC was to be administered for a minimum of 30 minutes and, if medically warranted, could continue beyond 96 hours at the investigator's discretion.
Overall Study STARTED	51	53
Overall Study mITT (Dosed & Have Confirmed AHF)	44	41
Overall Study COMPLETED	45	48
Overall Study NOT COMPLETED	6	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Clevidipine Clevidipine (0.5 mg/mL in 20% lipid emulsion) was administered intravenously via a single dedicated line to all patients randomized to the clevidipine arm. Clevidipine was titrated to effect thereafter by doubling the dose every 3 minutes, per physician discretion and as tolerated by the patient, until the desired SBP target range was attained. The infusion rate could then be increased or decreased as needed in order to maintain blood pressure for minimum of 30 minutes and a maximum duration of 96 hours. The minimum infusion rate was 1 mg/h and maximum infusion rate was 32 mg/h.	Standard of Care The selection of the standard of care (SOC) IV antihypertensive treatment agent was at the discretion of the investigator. The infusion was administered per the institution's treatment practice. Dose titrations were to be performed to the maximum allowed or tolerated dose in order to achieve SBP control within the patient-specified SBP target range within the first 30 minutes. SOC was to be administered for a minimum of 30 minutes and, if medically warranted, could continue beyond 96 hours at the investigator's discretion.
Overall Study Withdrew Consent	1	0
Overall Study Lost to Follow-up	2	3
Overall Study Death	3	2

Baseline Characteristics

Clevidipine in the Treatment of Blood Pressure in Patients With Acute Heart Failure (PRONTO)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Clevidipine Emulsion n=51 Participants All randomized and eligible patients who received any dose of clevidipine.	SOC IV Antihypertensive Therapy n=53 Participants All randomized and eligible patients who received any SOC dose.	Total n=104 Participants Total of all reporting groups
Age, Continuous	61.8 years STANDARD_DEVIATION 14.95 • n=5 Participants	60.2 years STANDARD_DEVIATION 14.89 • n=7 Participants	61.0 years STANDARD_DEVIATION 14.87 • n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	29 Participants n=7 Participants	54 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	24 Participants n=7 Participants	50 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	50 Participants n=5 Participants	53 Participants n=7 Participants	103 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	39 Participants n=5 Participants	44 Participants n=7 Participants	83 Participants n=5 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	9 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Systolic Blood Pressure (SBP)	188.2 mm Hg STANDARD_DEVIATION 25.02 • n=5 Participants	184.8 mm Hg STANDARD_DEVIATION 21.92 • n=7 Participants	186.5 mm Hg STANDARD_DEVIATION 23.44 • n=5 Participants
Diastolic Blood Pressure (DBP)	102.2 mm Hg STANDARD_DEVIATION 24.14 • n=5 Participants	99.2 mm Hg STANDARD_DEVIATION 24.28 • n=7 Participants	100.7 mm Hg STANDARD_DEVIATION 24.14 • n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Outcome measures
Measure	Clevidipine n=44 Participants Clevidipine was titrated to effect thereafter by doubling the dose every 3 minutes, per physician discretion and as tolerated by the patient, until the desired SBP target range was attained. The infusion rate could then be increased or decreased as needed in order to maintain blood pressure for minimum of 30 minutes and a maximum duration of 96 hours. The minimum infusion rate was 1 mg/h and maximum infusion rate was 32 mg/h.	Standard of Care n=41 Participants The selection of the standard of care (SOC) IV antihypertensive treatment agent was at the discretion of the investigator. The infusion was administered per the institution's treatment practice. Dose titrations were to be performed to the maximum allowed or tolerated dose in order to achieve SBP control within the patient-specified SBP target range within the first 30 minutes. SOC was to be administered for a minimum of 30 minutes and, if medically warranted, could continue beyond 96 hours at the investigator's discretion.
Time to First Achieve Initial Prespecified SBP Target Range and 15% Reduction From Baseline Within First 30 Minutes	15.0 Minutes Interval 15.0 to 21.0	NA Minutes NA=Not Reached: Median time to achieve this goal could not be determined in the SOC IV therapy group because less than 50% (15/41; 36.6%) of patients achieved both the pre-specified target range and a 15% reduction in SBP within the first 30 minutes.

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Clevidipine n=44 Participants Clevidipine was titrated to effect thereafter by doubling the dose every 3 minutes, per physician discretion and as tolerated by the patient, until the desired SBP target range was attained. The infusion rate could then be increased or decreased as needed in order to maintain blood pressure for minimum of 30 minutes and a maximum duration of 96 hours. The minimum infusion rate was 1 mg/h and maximum infusion rate was 32 mg/h.	Standard of Care n=41 Participants The selection of the standard of care (SOC) IV antihypertensive treatment agent was at the discretion of the investigator. The infusion was administered per the institution's treatment practice. Dose titrations were to be performed to the maximum allowed or tolerated dose in order to achieve SBP control within the patient-specified SBP target range within the first 30 minutes. SOC was to be administered for a minimum of 30 minutes and, if medically warranted, could continue beyond 96 hours at the investigator's discretion.
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 Interval 57.0 to 83.9	36.6 Percentage of patients Interval 21.8 to 51.3

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Clevidipine n=44 Participants Clevidipine was titrated to effect thereafter by doubling the dose every 3 minutes, per physician discretion and as tolerated by the patient, until the desired SBP target range was attained. The infusion rate could then be increased or decreased as needed in order to maintain blood pressure for minimum of 30 minutes and a maximum duration of 96 hours. The minimum infusion rate was 1 mg/h and maximum infusion rate was 32 mg/h.	Standard of Care n=41 Participants The selection of the standard of care (SOC) IV antihypertensive treatment agent was at the discretion of the investigator. The infusion was administered per the institution's treatment practice. Dose titrations were to be performed to the maximum allowed or tolerated dose in order to achieve SBP control within the patient-specified SBP target range within the first 30 minutes. SOC was to be administered for a minimum of 30 minutes and, if medically warranted, could continue beyond 96 hours at the investigator's discretion.
Percentage Reaching Prespecified Target Range Without Falling Below Lower Limit of Target Range Within First 30 Minutes	45.5 Percentage of patients Interval 30.7 to 60.2	51.2 Percentage of patients Interval 35.9 to 66.5

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Clevidipine n=44 Participants Clevidipine was titrated to effect thereafter by doubling the dose every 3 minutes, per physician discretion and as tolerated by the patient, until the desired SBP target range was attained. The infusion rate could then be increased or decreased as needed in order to maintain blood pressure for minimum of 30 minutes and a maximum duration of 96 hours. The minimum infusion rate was 1 mg/h and maximum infusion rate was 32 mg/h.	Standard of Care n=41 Participants The selection of the standard of care (SOC) IV antihypertensive treatment agent was at the discretion of the investigator. The infusion was administered per the institution's treatment practice. Dose titrations were to be performed to the maximum allowed or tolerated dose in order to achieve SBP control within the patient-specified SBP target range within the first 30 minutes. SOC was to be administered for a minimum of 30 minutes and, if medically warranted, could continue beyond 96 hours at the investigator's discretion.
SBP Area Under the Curve (AUC) Outside Prespecified Target Range	494.96 mm Hg x min/h Standard Deviation 428.554	966.15 mm Hg x min/h Standard Deviation 860.278

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Clevidipine n=44 Participants Clevidipine was titrated to effect thereafter by doubling the dose every 3 minutes, per physician discretion and as tolerated by the patient, until the desired SBP target range was attained. The infusion rate could then be increased or decreased as needed in order to maintain blood pressure for minimum of 30 minutes and a maximum duration of 96 hours. The minimum infusion rate was 1 mg/h and maximum infusion rate was 32 mg/h.	Standard of Care n=41 Participants The selection of the standard of care (SOC) IV antihypertensive treatment agent was at the discretion of the investigator. The infusion was administered per the institution's treatment practice. Dose titrations were to be performed to the maximum allowed or tolerated dose in order to achieve SBP control within the patient-specified SBP target range within the first 30 minutes. SOC was to be administered for a minimum of 30 minutes and, if medically warranted, could continue beyond 96 hours at the investigator's discretion.
Percentage Falling Below Lower Limit of SBP Target Range Within First 30 Minutes	34.1 Percentage of patients Interval 20.5 to 49.9	2.4 Percentage of patients Interval 0.1 to 12.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Clevidipine n=44 Participants Clevidipine was titrated to effect thereafter by doubling the dose every 3 minutes, per physician discretion and as tolerated by the patient, until the desired SBP target range was attained. The infusion rate could then be increased or decreased as needed in order to maintain blood pressure for minimum of 30 minutes and a maximum duration of 96 hours. The minimum infusion rate was 1 mg/h and maximum infusion rate was 32 mg/h.	Standard of Care n=41 Participants The selection of the standard of care (SOC) IV antihypertensive treatment agent was at the discretion of the investigator. The infusion was administered per the institution's treatment practice. Dose titrations were to be performed to the maximum allowed or tolerated dose in order to achieve SBP control within the patient-specified SBP target range within the first 30 minutes. SOC was to be administered for a minimum of 30 minutes and, if medically warranted, could continue beyond 96 hours at the investigator's discretion.
Percentage Falling Below Lower Limit of SBP Target Range at Any Time During Study	68.2 Percentage of patients Interval 52.4 to 81.4	70.7 Percentage of patients Interval 54.5 to 83.9

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Clevidipine n=44 Participants Clevidipine was titrated to effect thereafter by doubling the dose every 3 minutes, per physician discretion and as tolerated by the patient, until the desired SBP target range was attained. The infusion rate could then be increased or decreased as needed in order to maintain blood pressure for minimum of 30 minutes and a maximum duration of 96 hours. The minimum infusion rate was 1 mg/h and maximum infusion rate was 32 mg/h.	Standard of Care n=41 Participants The selection of the standard of care (SOC) IV antihypertensive treatment agent was at the discretion of the investigator. The infusion was administered per the institution's treatment practice. Dose titrations were to be performed to the maximum allowed or tolerated dose in order to achieve SBP control within the patient-specified SBP target range within the first 30 minutes. SOC was to be administered for a minimum of 30 minutes and, if medically warranted, could continue beyond 96 hours at the investigator's discretion.
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	-16.1 millimeters (mm) Standard Deviation 19.78
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	-22.8 millimeters (mm) Standard Deviation 21.03
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	-27.9 millimeters (mm) Standard Deviation 21.73
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	-34.6 millimeters (mm) Standard Deviation 23.38
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	-35.3 millimeters (mm) Standard Deviation 22.30
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	-40.5 millimeters (mm) Standard Deviation 21.69
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) Standard Deviation NA All patients in the clevidipine arm either completed the study or dropped out by the 12 hour time point.	-57.9 millimeters (mm) Standard Deviation 15.18
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	-50.1 millimeters (mm) Standard Deviation 26.09

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Clevidipine n=44 Participants Clevidipine was titrated to effect thereafter by doubling the dose every 3 minutes, per physician discretion and as tolerated by the patient, until the desired SBP target range was attained. The infusion rate could then be increased or decreased as needed in order to maintain blood pressure for minimum of 30 minutes and a maximum duration of 96 hours. The minimum infusion rate was 1 mg/h and maximum infusion rate was 32 mg/h.	Standard of Care n=41 Participants The selection of the standard of care (SOC) IV antihypertensive treatment agent was at the discretion of the investigator. The infusion was administered per the institution's treatment practice. Dose titrations were to be performed to the maximum allowed or tolerated dose in order to achieve SBP control within the patient-specified SBP target range within the first 30 minutes. SOC was to be administered for a minimum of 30 minutes and, if medically warranted, could continue beyond 96 hours at the investigator's discretion.
Time to Use Other IV Antihypertensives During the Study Drug Administration	NA Hours NA=Not estimable: Less than 50% of patients received a concomitant IV antihypertensive during study drug administration.	5.7 Hours Interval 1.7 to The upper limit of the 95% CI could not be calculated according to Samon and Lee, 1982.

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Clevidipine n=44 Participants Clevidipine was titrated to effect thereafter by doubling the dose every 3 minutes, per physician discretion and as tolerated by the patient, until the desired SBP target range was attained. The infusion rate could then be increased or decreased as needed in order to maintain blood pressure for minimum of 30 minutes and a maximum duration of 96 hours. The minimum infusion rate was 1 mg/h and maximum infusion rate was 32 mg/h.	Standard of Care n=41 Participants The selection of the standard of care (SOC) IV antihypertensive treatment agent was at the discretion of the investigator. The infusion was administered per the institution's treatment practice. Dose titrations were to be performed to the maximum allowed or tolerated dose in order to achieve SBP control within the patient-specified SBP target range within the first 30 minutes. SOC was to be administered for a minimum of 30 minutes and, if medically warranted, could continue beyond 96 hours at the investigator's discretion.
Percentage of Patients Who Received Any Alternative IV Antihypertensive Drug at Any Time During Study Drug Treatment	15.9 Percentage of patients Interval 5.1 to 26.7	51.2 Percentage of patients Interval 35.9 to 66.5

SECONDARY outcome

Timeframe: Initiation through termination of study drug (up to 96 hours)

Population: Safety population: All randomized and eligible patients who were dosed with study drug.

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.

Outcome measures

Outcome measures
Measure	Clevidipine n=51 Participants Clevidipine was titrated to effect thereafter by doubling the dose every 3 minutes, per physician discretion and as tolerated by the patient, until the desired SBP target range was attained. The infusion rate could then be increased or decreased as needed in order to maintain blood pressure for minimum of 30 minutes and a maximum duration of 96 hours. The minimum infusion rate was 1 mg/h and maximum infusion rate was 32 mg/h.	Standard of Care n=53 Participants The selection of the standard of care (SOC) IV antihypertensive treatment agent was at the discretion of the investigator. The infusion was administered per the institution's treatment practice. Dose titrations were to be performed to the maximum allowed or tolerated dose in order to achieve SBP control within the patient-specified SBP target range within the first 30 minutes. SOC was to be administered for a minimum of 30 minutes and, if medically warranted, could continue beyond 96 hours at the investigator's discretion.
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 Interval 1.2 to 16.2	1.9 Percentage of patients Interval 0.0 to 10.1

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Clevidipine n=44 Participants Clevidipine was titrated to effect thereafter by doubling the dose every 3 minutes, per physician discretion and as tolerated by the patient, until the desired SBP target range was attained. The infusion rate could then be increased or decreased as needed in order to maintain blood pressure for minimum of 30 minutes and a maximum duration of 96 hours. The minimum infusion rate was 1 mg/h and maximum infusion rate was 32 mg/h.	Standard of Care n=41 Participants The selection of the standard of care (SOC) IV antihypertensive treatment agent was at the discretion of the investigator. The infusion was administered per the institution's treatment practice. Dose titrations were to be performed to the maximum allowed or tolerated dose in order to achieve SBP control within the patient-specified SBP target range within the first 30 minutes. SOC was to be administered for a minimum of 30 minutes and, if medically warranted, could continue beyond 96 hours at the investigator's discretion.
Number of Patients That Require Intubation During Study Drug Administration up to 96 Hours	0 Patients	0 Patients

Adverse Events

Clevidipine

Serious events: 12 serious events

Other events: 20 other events

Deaths: 0 deaths

Standard of Care

Serious events: 10 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Clevidipine n=51 participants at risk Clevidipine was titrated to effect thereafter by doubling the dose every 3 minutes, per physician discretion and as tolerated by the patient, until the desired SBP target range was attained. The infusion rate could then be increased or decreased as needed in order to maintain blood pressure for minimum of 30 minutes and a maximum duration of 96 hours. The minimum infusion rate was 1 mg/h and maximum infusion rate was 32 mg/h.	Standard of Care n=53 participants at risk The selection of the standard of care (SOC) IV antihypertensive treatment agent was at the discretion of the investigator. The infusion was administered per the institution's treatment practice. Dose titrations were to be performed to the maximum allowed or tolerated dose in order to achieve SBP control within the patient-specified SBP target range within the first 30 minutes. SOC was to be administered for a minimum of 30 minutes and, if medically warranted, could continue beyond 96 hours at the investigator's discretion.
Gastrointestinal disorders Nausea	11.8% 6/51 • ▪ Non-serious Adverse Events (AEs) assessed up to 7 days following randomization or discharge whichever occurred first, regardless of causal relationship to the study drug ▪ Serious AEs (SAEs) assessed up to 30 days post-randomization into the study. AEs/SAEs were recorded in the electronic case report form (eCRF) by study personnel as a means of submitting required data to study Sponsor. The investigator was to complete an SAE Report (SAER) for each SAE regardless of causality by study medications, which was faxed to the Sponsor's safety vendor within 24 hours of when the SAE was recognized.	11.3% 6/53 • ▪ Non-serious Adverse Events (AEs) assessed up to 7 days following randomization or discharge whichever occurred first, regardless of causal relationship to the study drug ▪ Serious AEs (SAEs) assessed up to 30 days post-randomization into the study. AEs/SAEs were recorded in the electronic case report form (eCRF) by study personnel as a means of submitting required data to study Sponsor. The investigator was to complete an SAE Report (SAER) for each SAE regardless of causality by study medications, which was faxed to the Sponsor's safety vendor within 24 hours of when the SAE was recognized.
Nervous system disorders Headache	21.6% 11/51 • ▪ Non-serious Adverse Events (AEs) assessed up to 7 days following randomization or discharge whichever occurred first, regardless of causal relationship to the study drug ▪ Serious AEs (SAEs) assessed up to 30 days post-randomization into the study. AEs/SAEs were recorded in the electronic case report form (eCRF) by study personnel as a means of submitting required data to study Sponsor. The investigator was to complete an SAE Report (SAER) for each SAE regardless of causality by study medications, which was faxed to the Sponsor's safety vendor within 24 hours of when the SAE was recognized.	24.5% 13/53 • ▪ Non-serious Adverse Events (AEs) assessed up to 7 days following randomization or discharge whichever occurred first, regardless of causal relationship to the study drug ▪ Serious AEs (SAEs) assessed up to 30 days post-randomization into the study. AEs/SAEs were recorded in the electronic case report form (eCRF) by study personnel as a means of submitting required data to study Sponsor. The investigator was to complete an SAE Report (SAER) for each SAE regardless of causality by study medications, which was faxed to the Sponsor's safety vendor within 24 hours of when the SAE was recognized.
Psychiatric disorders Insomnia	5.9% 3/51 • ▪ Non-serious Adverse Events (AEs) assessed up to 7 days following randomization or discharge whichever occurred first, regardless of causal relationship to the study drug ▪ Serious AEs (SAEs) assessed up to 30 days post-randomization into the study. AEs/SAEs were recorded in the electronic case report form (eCRF) by study personnel as a means of submitting required data to study Sponsor. The investigator was to complete an SAE Report (SAER) for each SAE regardless of causality by study medications, which was faxed to the Sponsor's safety vendor within 24 hours of when the SAE was recognized.	0.00% 0/53 • ▪ Non-serious Adverse Events (AEs) assessed up to 7 days following randomization or discharge whichever occurred first, regardless of causal relationship to the study drug ▪ Serious AEs (SAEs) assessed up to 30 days post-randomization into the study. AEs/SAEs were recorded in the electronic case report form (eCRF) by study personnel as a means of submitting required data to study Sponsor. The investigator was to complete an SAE Report (SAER) for each SAE regardless of causality by study medications, which was faxed to the Sponsor's safety vendor within 24 hours of when the SAE was recognized.

Additional Information

Jason Campagna

The Medicines Company

Phone: 973-290-6199

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After initial multicenter results communications are published, or after 12 months from study closure (whichever occurs first), sponsor can review results communications prior to submission and can embargo submissions for a period of 45 days from the time submitted to the sponsor for review, agreeing to resolve differences of opinion or interpretation through scientific debate. Sponsor can request further delay for an additional 90 days to file any patent applications if deemed necessary.
Publication restrictions are in place

Restriction type: OTHER