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

Hypertension Clinical Trial

— PRONTO II  

Official title:

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)

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04592380
• Other study ID #: MDCO-CLV-13-03
• Secondary ID: PRONTO II
• Status: Withdrawn
• Phase: Phase 3
• Start date: August 2014
• Est. completion date: November 2016

Study information

• Verified date: October 2020
• Source: The Medicines Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 2016
• Est. primary completion date: February 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Heart Failure
• Dyspnea
• Heart Failure
• Hypertension

Intervention

Drug:
• Stage 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.
• Stage 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.
• Stage 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.
• Stage 2: Standard of Care (open-label)
Transition to oral antihypertensive medication from SOC IV antihypertensive is per institutional practice.

Locations

Country	Name	City	State
United States	Maimonides Medical Center	Brooklyn	New York
United States	New York Methodist Hospital	Brooklyn	New York
United States	University of Cincinnati	Cincinnati	Ohio
United States	Duke University Hospital	Durham	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	Drug Research and Analysis Corporation/Jackson Hospital	Montgomery	Alabama
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Stony Brook University and Medical Center	Stony Brook	New York
United States	University of Arizona Medical Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
The Medicines Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Median time to reach target BP within the first 30 minutes		Study drug initiation through the first 30 minutes of study drug infusion
Secondary	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