Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT00803634 | Clevidipine in the Treatment of Blood Pressure in Patients With Acute Heart Failure (PRONTO) | PHASE3 | COMPLETED | 117 | — | — | Dec 1, 2008 | Mar 1, 2012 | Aug 29, 2014 | 13 | United States, France +1 |
| NCT00666328 | Clevidipine in the Treatment of Patients With Acute Hypertension and Intracerebral Hemorrhage (ACCELERATE) | PHASE3 | COMPLETED | 37 | — | — | Jun 1, 2008 | Apr 1, 2010 | Aug 29, 2014 | 17 | United States, Germany |
| NCT00369837 | Clevidipine in the Treatment of Patients With Severe Hypertension (VELOCITY) | PHASE3 | COMPLETED | 131 | — | — | Sep 1, 2006 | Feb 1, 2007 | May 22, 2014 | 14 | United States |
| NCT00093912 | Clevidipine in the Perioperative Treatment of Hypertension (ECLISPE-SNP) | PHASE3 | COMPLETED | 739 | — | — | Jun 1, 2004 | Nov 1, 2006 | May 6, 2014 | 29 | United States |
| NCT00093925 | Clevidipine in the Postoperative Treatment of Hypertension (ECLIPSE-NIC) | PHASE3 | COMPLETED | 739 | — | — | May 1, 2004 | Sep 1, 2006 | May 6, 2014 | 9 | United States |
| NCT00093886 | Clevidipine in the Perioperative Treatment of Hypertension (ECLIPSE-NTG) | PHASE3 | COMPLETED | 629 | — | — | Apr 1, 2004 | Apr 1, 2005 | May 6, 2014 | 28 | United States |
| NCT00093249 | Study of Clevidipine Assessing Its Preoperative Antihypertensive Effect in Cardiac Surgery (ESCAPE-1) | PHASE3 | COMPLETED | 105 | — | — | Jan 1, 2004 | Nov 1, 2004 | Aug 22, 2014 | 12 | United States |
| NCT00093262 | Study of Clevidipine Assessing Its Postoperative Antihypertensive Effect in Cardiac Surgery (ESCAPE-2) | PHASE3 | COMPLETED | 206 | — | — | Dec 1, 2003 | Oct 1, 2004 | May 8, 2014 | 15 | United States |
| NCT00799604 | Clevidipine Bolus Administration in the Treatment of Hypertensive Patients Undergoing Cardiac Surgery (SPRINT) | PHASE2 | COMPLETED | 30 | — | — | Nov 1, 2008 | Oct 1, 2009 | Aug 29, 2014 | 2 | United States |
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.
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.
The median time, in minutes, was estimated with its two-tailed 95% confidence interval from the time of the initiation of clevidipine infusion until the first observed SBP was achieved in the target range of ≤160 mmHg to ≥140 mmHg within the first 30 minutes of clevidipine treatment. If patients did not reach the blood pressure target range within the first 30 minutes, their data was considered censored at 30 minutes. If another IV and/or oral antihypertensive agent indicated for hypertension was administered less than 30 minutes prior to achieving the endpoint, the data was considered censored at the time when the additional or alternative antihypertensive agent was given.
discontinuation of study drug categorized according to the following reasons: * Bailout for lack of efficacy * Bailout for safety reason(s) * Bailout due to treatment failure
Blood Pressure was measured at 60, 45, 30, 0 seconds prior to first Bolus dose (Bolus 1), and every 5 seconds after Bolus 1 for 15 minutes. Baseline SBP of Bolus 1 is defined as, 'median of all measurements prior to or at the start of Bolus 1'. Locally weighted scatterplot smoothing (LOWESS) method was used to determine the minimum SBP value for each patient. Maximum absolute change is the minimum SBP value within 15 minutes from bolus 1 minus baseline value.
Blood Pressure was measured at 60, 45, 30, 0 seconds prior to first Bolus dose (Bolus 1), and every 5 seconds after Bolus 1 for 15 minutes. Baseline SBP of Bolus 1 is defined as, 'median of all measurements prior to or at the start of Bolus 1'. Locally weighted scatterplot smoothing (LOWESS) method was used to determine the minimum SBP value for each patient. Maximum percent change is defined as the maximum absolute change divided by the baseline value of bolus 1 and multiplied by 100.
| Arm | Type | Description |
|---|---|---|
| Clevidipine | EXPERIMENTAL | 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 infused at an initial rate of 2 mg/h for the first 3 minutes. If blood pressure was not in the target range at 3 minutes, clevidipine was titrated to effect thereafter by doubling the dose every 3 min, per physician discretion and as tolerated by the patient until the desired effect until the SBP target range was attained. Once target range was achieved, the infusion rate could be increased or decreased as needed 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 IV antihypertensive | ACTIVE_COMPARATOR | For patients randomized to standard of care (SOC) IV antihypertensive treatment, a continuous infusion of an intravenous antihypertensive agent represented standard of care. The selection of treatment was at the discretion of the investigator. The infusion was to be administered according to the institution's treatment practice. |
| sodium nitroprusside | ACTIVE_COMPARATOR | Sodium nitroprusside (SNP) was initiated after insertion of an arterial line upon the occurrence of perioperative hypertension, as determined by the investigator, and was administered intravenously as per institutional practice. Treatment was maintained as long as was deemed clinically necessary or until discharge from the ICU. |
| nicardipine | ACTIVE_COMPARATOR | Nicardipine (NIC) was initiated after insertion of an arterial line upon the occurrence of postoperative hypertension, as determined by the investigator, and was administered intravenously as per institutional practice. Treatment was maintained as long as was deemed clinically necessary or until discharge from the ICU. |
| nitroglycerin | ACTIVE_COMPARATOR | Nitroglycerin (NTG) was initiated after insertion of an arterial line upon the occurrence of perioperative hypertension, as determined by the investigator, and was administered intravenously as per institutional practice. Treatment was maintained as long as was deemed clinically necessary or until discharge from the ICU. |
| placebo | PLACEBO_COMPARATOR | Placebo consisted of 20% lipid emulsion (the same lipid vehicle used for clevidipine) administered in a blinded fashion intravenously following the same study drug administration guidelines as with clevidipine study drug administration guidelines. As with clevidipine, placebo was to be administered for a minimum of 30 minutes, unless bailout occurred, and up to a maximum of one hour. |
| Name | Type | Description |
|---|---|---|
| Clevidipine | DRUG | 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. |
| Standard of Care IV antihypertensive | DRUG | 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. |
| sodium nitroprusside | DRUG | - |
| nicardipine | DRUG | - |
| nitroglycerin | DRUG | - |
| placebo | DRUG | Placebo (20% lipid emulsion - vehicle) will be administered intravenously in a fashion identical to clevidipine as described above. |
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 leas...