Clevidipine vs Placebo or Standard of Care for Dyspnea and Blood Pressure Control in AHF

A Randomized Parallel Group Controlled Comparison Study of Clevidipine Versus Placebo or Standard of Care for Dyspnea and Blood Pressure Control in Acute Heart Failure (PRONTO II)

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.

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.

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