Acute Heart Failure, Dyspnea, Hypertension
Conditions
Brief summary
The purpose of this study is to evaluate dyspnea improvement and other parameters of efficacy and safety in acute heart failure (AHF) patients receiving an intravenous (IV) infusion of clevidipine in comparison to standard of care (SOC) and placebo.
Detailed description
Randomization will occur in two stages. Stage 1 patients will be randomized in a double-blinded manner in a 1:1 ratio to receive either clevidipine or placebo IV infusion. Upon completion of Stage 1, Stage 2 patients will be randomized in an open-label manner in a 1:1 ratio to receive either clevidipine or standard of care (SOC) IV infusion. At the time of randomization, a patient-specific, prespecified systolic blood pressure (SBP) target range will be determined and recorded prior to study drug treatment. Up to 500 patients may be enrolled to achieve a total of 100 Stage 1 and 300 Stage 2 patients with confirmed AHF per protocol. A Data Safety Monitoring Board will be utilized periodically throughout the study to monitor the safety of patients. Adverse events will be assessed for 7 days post-study randomization or hospital discharge, whichever occurred sooner. Serious adverse events (SAEs) were assessed for 30 days following study randomization.
Interventions
DRUGStage 1: Clevidipine (double-blinded)
Patients may be transitioned to an oral antihypertensive medication as necessary. When such a transition is required, then approximately 1 hour prior to the anticipated cessation of the double-blinded clevidipine infusion, an oral antihypertensive agent may be administered. The clevidipine infusion may be down-titrated or terminated at any time following administration of the oral agent, in order to achieve the desired BP level.
DRUGStage 1: Placebo (double-blinded)
Patients may be transitioned to an oral antihypertensive medication as necessary. When such a transition is required, then approximately 1 hour prior to the anticipated cessation of the double-blinded placebo infusion, an oral antihypertensive agent may be administered. The placebo infusion may be down-titrated or terminated at any time following administration of the oral agent, in order to achieve the desired BP level.
DRUGStage 2: Clevidipine (open-label)
Patients may be transitioned to an oral antihypertensive medication as necessary. When such a transition is required, then approximately 1 hour prior to the anticipated cessation of the clevidipine infusion, an oral antihypertensive agent may be administered. The clevidipine infusion may be down-titrated or terminated at any time following administration of the oral agent, in order to achieve the desired BP level.
DRUGStage 2: Standard of Care (open-label)
Transition to oral antihypertensive medication from SOC IV antihypertensive is per institutional practice.
Sponsors
The Medicines Company
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older and providing * Presentation consistent with AHF as manifest by pulmonary congestion * Dyspnea score (sitting) ≥ 50 mm on a 100 mm visual analog scale * In Stage 1, baseline SBP ≥130 - 160 mmHg (measured immediately prior to initiation of study drug); in Stage 2, baseline SBP ≥ 130 mmHg
Exclusion criteria
* Administration of an IV or oral antihypertensive agent within the previous 2 hours of randomization (short acting oral or sublingual nitrates are permitted) * Chest pain and/or electrocardiogram (ECG) with ST segment changes consistent with acute coronary syndrome * Known or suspected aortic dissection * Acute myocardial infarction (AMI) within the prior 14 days * Dialysis-dependent renal failure * Requirement for immediate endotracheal intubation * Suspected pregnancy or breast feeding female * Intolerance or allergy to calcium channel blockers * Allergy to soybean oil or lecithin * Known liver failure, cirrhosis or pancreatitis * 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 |
|---|---|
| Change in dyspnea VAS score from baseline at 3 hours post-baseline | Immediately prior to study drug administration (baseline) to 3 hours post-baseline |
Secondary
| Measure | Time frame |
|---|---|
| Median time to reach target BP within the first 30 minutes | Study drug initiation through the first 30 minutes of study drug infusion |
| Percentage of patients who require rescue therapy (ie, receive any alternative IV antihypertensive drug) within the first 30 minutes | Study drug initiation through the first 30 minutes of study drug infusion |
Countries
United States
Outcome results
None listed