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

Condition(s) targeted: Hypertension; Heart Failure

Intervention: Clevidipine (Drug); Standard of Care IV antihypertensive (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: The Medicines Company

Official(s) and/or principal investigator(s):
W. Frank Peacock, MD, Principal Investigator, Affiliation: The Cleveland Clinic

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.

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

Time to First Achieve Initial Prespecified SBP Target Range and 15% Reduction From Baseline Within First 30 Minutes

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

Secondary outcome:

Percentage Reaching Prespecified Target Range Without Falling Below Lower Limit of Target Range Within First 30 Minutes

SBP Area Under the Curve (AUC) Outside Prespecified Target Range

Percentage Falling Below Lower Limit of SBP Target Range Within First 30 Minutes

Percentage Falling Below Lower Limit of SBP Target Range at Any Time During Study

Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point

Time to Use Other IV Antihypertensives During the Study Drug Administration

Percentage of Patients Who Received Any Alternative IV Antihypertensive Drug at Any Time During Study Drug Treatment

Percentage of Patients With at Least One Episode of SBP < 90 mm Hg During Study Drug Administration (up to 96 Hours)

Number of Patients That Require Intubation During Study Drug Administration up to 96 Hours

Detailed description: 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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

Hopial AP-HP Hotel-Dieu, Paris 75004, France

Hopital AP-HP La Pitie Sapetriere, Paris 75013, France

Hopital AP-HP Lariboisiere Urgencies-SMUR, Paris 75475, France

Charité - Universitätsmedizin Berlin, Berlin 13353, Germany

Jackson Hospital, Montgomery, Alabama 36106, United States

Centinela Hospital, Inglewood, California 90301, United States

Louisiana State University Health Sciences Center, Baton Rouge, Louisiana 70805, United States

Louisiana State University Health Sciences Center - Emergency Medicine, New Orleans, Louisiana 70112, United States

Washington University School of Medicine, St. Louis, Missouri 63110, United States

Stony Brook University and Medical Center, Stony Brook, New York 11794, United States

Duke University Medical Center, Durham, North Carolina 27710, United States

University of Cincinnati, Cincinnati, Ohio 45267, United States

The Cleveland Clinic, Cleveland, Ohio 44195, United States

Starting date: December 2008
Last updated: August 21, 2014