Clinical trial NCT04592380: Clevidipine vs Placebo or Standard of Care for Dyspnea and Blood Pressure Control in AHF
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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Dyspnea
Hypertension
Acute Heart Failure
Lead sponsor: The Medicines Company
Sponsor class: INDUSTRY
First posted: 2020-10-19
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in dyspnea VAS score from baseline at 3 hours post-baseline
timeFrame: Immediately prior to study drug administration (baseline) to 3 hours post-baseline
Secondary outcomes:
measure: Median time to reach target BP within the first 30 minutes
timeFrame: Study drug initiation through the first 30 minutes of study drug infusion
measure: Percentage of patients who require rescue therapy (ie, receive any alternative IV antihypertensive drug) within the first 30 minutes
timeFrame: Study drug initiation through the first 30 minutes of study drug infusion
Other outcomes:
Locations:
city: Montgomery
country: United States
facility: Drug Research and Analysis Corporation/Jackson Hospital
state: Alabama
city: Tucson
country: United States
facility: University of Arizona Medical Center
state: Arizona
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Brooklyn
country: United States
facility: New York Methodist Hospital
state: New York
city: Brooklyn
country: United States
facility: Maimonides Medical Center
state: New York
city: Stony Brook
country: United States
facility: Stony Brook University and Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
Study officials:
affiliation: Baylor College of Medicine
name: William F Peacock, MD, FACEP
role: PRINCIPAL_INVESTIGATOR
References: