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

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ClinicalTrials.gov Identifier: NCT00803634
Recruitment Status : Completed
First Posted : December 5, 2008
Results First Posted : August 19, 2014
Last Update Posted : August 29, 2014
Sponsor:
Information provided by (Responsible Party):
The Medicines Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Hypertension
Heart Failure
Interventions Drug: Clevidipine
Drug: Standard of Care IV antihypertensive
Enrollment 117
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.
Arm/Group Title Clevidipine Standard of Care
Hide Arm/Group Description 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. 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.
Period Title: Overall Study
Started 51 [1] 53 [2]
mITT (Dosed & Have Confirmed AHF) 44 [3] 41 [4]
Completed 45 [1] 48 [2]
Not Completed 6 5
Reason Not Completed
Withdrew Consent             1             0
Lost to Follow-up             2             3
Death             3             2
[1]
All patients dosed with clevidipine [Safety population]
[2]
All patients dosed with SOC antihypertensive therapy [Safety population]
[3]
All patients dosed with clevidipine and confirmed to have AHF [mITT population]
[4]
All patients dosed with SOC antihypertensive therapy and confirmed to have AHF [mITT population]
Arm/Group Title Clevidipine Emulsion SOC IV Antihypertensive Therapy Total
Hide Arm/Group Description All randomized and eligible patients who received any dose of clevidipine. All randomized and eligible patients who received any SOC dose. Total of all reporting groups
Overall Number of Baseline Participants 51 53 104
Hide Baseline Analysis Population Description
Safety Population: Includes all patients dosed with clevidipine (for patients randomized to the clevidipine arm) of standard of care (SOC) (for patients randomized to the SOC arm) continuous IV antihypertensive therapy.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 51 participants 53 participants 104 participants
61.8  (14.95) 60.2  (14.89) 61.0  (14.87)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 53 participants 104 participants
Female
25
  49.0%
29
  54.7%
54
  51.9%
Male
26
  51.0%
24
  45.3%
50
  48.1%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 53 participants 104 participants
Hispanic or Latino
1
   2.0%
0
   0.0%
1
   1.0%
Not Hispanic or Latino
50
  98.0%
53
 100.0%
103
  99.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 51 participants 53 participants 104 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
39
  76.5%
44
  83.0%
83
  79.8%
White
12
  23.5%
9
  17.0%
21
  20.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Systolic Blood Pressure (SBP)  
Mean (Standard Deviation)
Unit of measure:  Mm Hg
Number Analyzed 51 participants 53 participants 104 participants
188.2  (25.02) 184.8  (21.92) 186.5  (23.44)
Diastolic Blood Pressure (DBP)  
Mean (Standard Deviation)
Unit of measure:  Mm Hg
Number Analyzed 51 participants 53 participants 104 participants
102.2  (24.14) 99.2  (24.28) 100.7  (24.14)
1.Primary Outcome
Title Time to First Achieve Initial Prespecified SBP Target Range and 15% Reduction From Baseline Within First 30 Minutes
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Clevidipine Standard of Care
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 44 41
Median (95% Confidence Interval)
Unit of Measure: Minutes
15.0
(15.0 to 21.0)
NA [1] 
(NA to NA)
[1]
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.
2.Primary Outcome
Title 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
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Clevidipine Standard of Care
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 44 41
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of patients
70.5
(57.0 to 83.9)
36.6
(21.8 to 51.3)
3.Secondary Outcome
Title Percentage Reaching Prespecified Target Range Without Falling Below Lower Limit of Target Range Within First 30 Minutes
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Clevidipine SOC IV Therapy
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 44 41
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of patients
45.5
(30.7 to 60.2)
51.2
(35.9 to 66.5)
4.Secondary Outcome
Title SBP Area Under the Curve (AUC) Outside Prespecified Target Range
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Clevidipine Standard of Care
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 44 41
Mean (Standard Deviation)
Unit of Measure: mm Hg x min/h
494.96  (428.554) 966.15  (860.278)
5.Secondary Outcome
Title Percentage Falling Below Lower Limit of SBP Target Range Within First 30 Minutes
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Clevidipine Standard of Care
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 44 41
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of patients
34.1
(20.5 to 49.9)
2.4
(0.1 to 12.9)
6.Secondary Outcome
Title Percentage Falling Below Lower Limit of SBP Target Range at Any Time During Study
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Clevidipine Standard of Care
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 44 41
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of patients
68.2
(52.4 to 81.4)
70.7
(54.5 to 83.9)
7.Secondary Outcome
Title Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Clevidipine Standard of Care
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 44 41
Mean (Standard Deviation)
Unit of Measure: millimeters (mm)
Baseline Through Initial 15 Min- CLV n=44;SOC n=38 -18.6  (17.49) -16.1  (19.78)
Baseline Through Initial 30 Min- CLV n=43;SOC n=39 -28.8  (19.94) -22.8  (21.03)
Baseline Through Initial 45 Min- CLV n=43;SOC n=39 -37.1  (20.87) -27.9  (21.73)
Baseline Through Initial 1 H- CLV n=41;SOC n=38 -43.6  (21.74) -34.6  (23.38)
Baseline Through Initial 2 H- CLV n=29;SOC n=29 -45.2  (22.66) -35.3  (22.30)
Baseline Through Initial 3 H- CLV n=14;SOC n=22 -47.9  (16.57) -40.5  (21.69)
Baseline Through Initial 12 H- CLV n=0;SOC n=7 NA [1]   (NA) -57.9  (15.18)
Baseline Through 1 H Post Drug- CLV n=41;SOC n=33 -50.1  (23.22) -50.1  (26.09)
[1]
All patients in the clevidipine arm either completed the study or dropped out by the 12 hour time point.
8.Secondary Outcome
Title Time to Use Other IV Antihypertensives During the Study Drug Administration
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Clevidipine Standard of Care
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 44 41
Median (95% Confidence Interval)
Unit of Measure: Hours
NA [1] 
(NA to NA)
5.7 [2] 
(1.7 to NA)
[1]
NA=Not estimable: Less than 50% of patients received a concomitant IV antihypertensive during study drug administration.
[2]
The upper limit of the 95% CI could not be calculated according to Samon and Lee, 1982.
9.Secondary Outcome
Title Percentage of Patients Who Received Any Alternative IV Antihypertensive Drug at Any Time During Study Drug Treatment
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Clevidipine Standard of Care
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 44 41
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of patients
15.9
(5.1 to 26.7)
51.2
(35.9 to 66.5)
10.Secondary Outcome
Title Percentage of Patients With at Least One Episode of SBP < 90 mm Hg During Study Drug Administration (up to 96 Hours)
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety population: All randomized and eligible patients who were dosed with study drug.
Arm/Group Title Clevidipine Standard of Care
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 51 53
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of patients
5.9
(1.2 to 16.2)
1.9
(0.0 to 10.1)
11.Secondary Outcome
Title Number of Patients That Require Intubation During Study Drug Administration up to 96 Hours
Hide Description 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)
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Clevidipine Standard of Care
Hide Arm/Group Description:
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.
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 Number of Participants Analyzed 44 41
Measure Type: Number
Unit of Measure: Patients
0 0
Time Frame ▪ 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.
Adverse Event Reporting Description 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.
 
Arm/Group Title Clevidipine Standard of Care
Hide Arm/Group Description 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. 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.
All-Cause Mortality
Clevidipine Standard of Care
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Clevidipine Standard of Care
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/51 (23.53%)      10/53 (18.87%)    
Cardiac disorders     
Acute coronary syndrome  1  1/51 (1.96%)  1 0/53 (0.00%)  0
Angina pectoris  1  1/51 (1.96%)  1 0/53 (0.00%)  0
Atrial fibrillation  2  1/51 (1.96%)  1 0/53 (0.00%)  0
Cardiac failure  2  1/51 (1.96%)  1 1/53 (1.89%)  1
Cardiac failure congestive  2  4/51 (7.84%)  4 2/53 (3.77%)  2
Cardio-respiratory arrest  2  0/51 (0.00%)  0 1/53 (1.89%)  1
Coronary artery disease  2  0/51 (0.00%)  0 1/53 (1.89%)  1
Myocardial infarction  2  0/51 (0.00%)  0 1/53 (1.89%)  1
Sick sinus syndrome  2  0/51 (0.00%)  0 1/53 (1.89%)  1
Infections and infestations     
Urosepsis  2  0/51 (0.00%)  0 1/53 (1.89%)  1
Injury, poisoning and procedural complications     
Fall  2  0/51 (0.00%)  0 1/53 (1.89%)  1
Fracture  2  1/51 (1.96%)  1 0/53 (0.00%)  0
Metabolism and nutrition disorders     
Hypoglycemia  2  1/51 (1.96%)  1 0/53 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Prostate cancer  2  1/51 (1.96%)  1 0/53 (0.00%)  0
Renal and urinary disorders     
Renal failure  2  0/51 (0.00%)  0 1/53 (1.89%)  1
Renal failure chronic  2  1/51 (1.96%)  1 1/53 (1.89%)  1
Respiratory, thoracic and mediastinal disorders     
Asthma  2  0/51 (0.00%)  0 1/53 (1.89%)  1
Chronic obstructive pulmonary disease  2  1/51 (1.96%)  1 0/53 (0.00%)  0
Dyspnea  2  0/51 (0.00%)  0 1/53 (1.89%)  1
Pleural effusion  2  1/51 (1.96%)  1 0/53 (0.00%)  0
Respiratory distress  2  0/51 (0.00%)  0 1/53 (1.89%)  1
Respiratory failure  2  2/51 (3.92%)  2 1/53 (1.89%)  1
Vascular disorders     
Aortic dissection  2  1/51 (1.96%)  1 0/53 (0.00%)  0
Hemorrhage  2  1/51 (1.96%)  1 0/53 (0.00%)  0
Hypertension  2  0/51 (0.00%)  0 1/53 (1.89%)  1
Hypertensive crisis  2  1/51 (1.96%)  1 0/53 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 11.0
2
Term from vocabulary, MedDRA (11.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Clevidipine Standard of Care
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   20/51 (39.22%)      19/53 (35.85%)    
Gastrointestinal disorders     
Nausea  1  6/51 (11.76%)  6/53 (11.32%) 
Nervous system disorders     
Headache  1  11/51 (21.57%)  13/53 (24.53%) 
Psychiatric disorders     
Insomnia  1  3/51 (5.88%)  0/53 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (11.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Jason Campagna
Organization: The Medicines Company
Phone: 973-290-6199
EMail: jason.campagna@themedco.com
Layout table for additonal information
Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT00803634    
Other Study ID Numbers: TMC-CLV-08-01
TMC-CLV-08-01 ( Other Identifier: Sponsor )
First Submitted: December 3, 2008
First Posted: December 5, 2008
Results First Submitted: June 3, 2014
Results First Posted: August 19, 2014
Last Update Posted: August 29, 2014