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

A Safety and Efficacy Study of Blood Pressure Control in Acute Heart Failure - A Pilot Study (PRONTO)

The purpose of this study was to evaluate the efficacy and safety of intravenous (IV) clevidipine as compared with standard of care IV antihypertensive agents for blood pressure (BP) lowering in patients with acute heart failure and elevated BP.

This study was an open-label randomized efficacy and safety pilot trial in patients with acute heart failure (AHF) and hypertension (systolic blood pressure [SBP] ≥160 mm Hg) requiring parenteral antihypertensive therapy. Eligible patients were randomized to receive clevidipine or standard of care (SOC) intravenous antihypertensive treatment in an open-label manner in a ratio of 1:1. At the time of randomization, a patient-specific, prespecified SBP target range was determined and be recorded, prior to study drug treatment. Information on the dosing regimen, use of additional or alternative agents and transition to oral therapy if needed is detailed in the study 'ARM' and 'INTERVENTION' sections.

A Data Safety Monitoring Board was utilized periodically throughout the study to monitor the safety of patients. Adverse events were assessed for 7 days post-study randomization or hospital discharge, whichever occured first. Serious adverse events (SAEs) were assessed for 30 days following study randomization. Subjects were contacted by telephone or in person up to 5 days after their 30-day time point to determine if any SAEs occurred following study drug treatment and to follow up on the Heath Economic assessments.

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 least 5 on a 10 cm visual analog scale (VAS)
• Required IV antihypertensive therapy to lower blood pressure
• Written informed consent

Exclusion Criteria:

• Administration of an agent (IV or oral) for the treatment of elevated BP within the previous 2 hours of randomization. (Previous short-acting non-IV nitrates, continuous positive airway pressure (CPAP), and bi-level positive airway pressure (BiPAP) were permitted)
• Chest pain and/or electrocardiogram with ST segment changes consistent with acute coronary syndrome
• Known or suspected aortic dissection
• Acute myocardial infarction within the prior 14 days
• Dialysis-dependant renal failure
• Requirement for immediate endotracheal intubation
• Positive pregnancy test, known pregnancy or breast feeding female
• Intolerance or allergy to calcium channel blockers
• Allergy to soybean oil or egg lecithin
• Known liver failure, cirrhosis or pancreatitis
• Prior directives against advanced life support
• Participation in other clinical research studies involving the evaluation of other investigational drugs or devices within 30 days of enrollment