Clinical trial NCT00803634: Clevidipine in the Treatment of Blood Pressure in Patients With Acute Heart Failure (PRONTO)
Official title: A Safety and Efficacy Study of Blood Pressure Control in Acute Heart Failure - A Pilot Study (PRONTO)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension
Heart Failure
Keywords: Hypertension
Antihypertensive Agent
Calcium Channel Blocker
Lead sponsor: The Medicines Company
Sponsor class: INDUSTRY
First posted: 2008-12-05
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility 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

Primary outcomes:
measure: Time to First Achieve Initial Prespecified SBP Target Range and 15% Reduction From Baseline Within First 30 Minutes
timeFrame: Initiation of study drug through the initial 30-minutes
measure: 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
timeFrame: Initiation of study drug through the initial 30-minutes
Secondary outcomes:
measure: Percentage Reaching Prespecified Target Range Without Falling Below Lower Limit of Target Range Within First 30 Minutes
timeFrame: Initiation of study drug through the initial 30-minutes
measure: SBP Area Under the Curve (AUC) Outside Prespecified Target Range
timeFrame: Initiation of study drug through end of monotherapy (up to 96 hours)
measure: Percentage Falling Below Lower Limit of SBP Target Range Within First 30 Minutes
timeFrame: Initiation of study drug through the initial 30-minutes
measure: Percentage Falling Below Lower Limit of SBP Target Range at Any Time During Study
timeFrame: Initiation through termination of study drug (up to 96 hours)
measure: Change From Baseline in Dyspnea (Measured By VAS) at Each Time Point
timeFrame: Baseline (immediately prior to study drug administration) through 1 hour after study drug termination
measure: Time to Use Other IV Antihypertensives During the Study Drug Administration
timeFrame: Initiation of study drug through any other concomitant IV antihypertensive agent administered, up to 96 hours
measure: Percentage of Patients Who Received Any Alternative IV Antihypertensive Drug at Any Time During Study Drug Treatment
timeFrame: Initiation through termination of study drug (up to 96 hours)
measure: Percentage of Patients With at Least One Episode of SBP < 90 mm Hg During Study Drug Administration (up to 96 Hours)
timeFrame: Initiation through termination of study drug (up to 96 hours)
measure: Number of Patients That Require Intubation During Study Drug Administration up to 96 Hours
timeFrame: Initiation through termination of study drug (up to 96 hours)
Other outcomes:
Locations:
city: Montgomery
country: United States
facility: Jackson Hospital
state: Alabama
city: Inglewood
country: United States
facility: Centinela Hospital
state: California
city: Baton Rouge
country: United States
facility: Louisiana State University Health Sciences Center
state: Louisiana
city: New Orleans
country: United States
facility: Louisiana State University Health Sciences Center - Emergency Medicine
state: Louisiana
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Stony Brook
country: United States
facility: Stony Brook University and Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: The Cleveland Clinic
state: Ohio
city: Paris
country: France
facility: Hopial AP-HP Hotel-Dieu
city: Paris
country: France
facility: Hopital AP-HP La Pitie Sapetriere
city: Paris
country: France
facility: Hopital AP-HP Lariboisiere Urgencies-SMUR
city: Berlin
country: Germany
facility: Charité - Universitätsmedizin Berlin
Study officials:
affiliation: The Cleveland Clinic
name: W. Frank Peacock, MD
role: PRINCIPAL_INVESTIGATOR
References: