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

NCT04592380 | Withdrawn Phase 3 DMC

• 2 other identifiers: MDCO-CLV-13-03PRONTO II
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 9

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.

Conditions

Dyspnea; Hypertension; Acute Heart Failure

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Median time to reach target BP within the first 30 minutes

  Study drug initiation through the first 30 minutes of study drug infusion

• 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

Study Arms (4)

Stage 1: Clevidipine (double-blinded)

EXPERIMENTAL

Clevidipine (0.5 mg/mL in 20% lipid emulsion) will be administered in a double-blinded fashion intravenously to all patients randomized to the clevidipine arm in Stage 1. Clevidipine will be initiated at an initial rate of 2 mg/h for the first 1.5 minutes (90 seconds) and titrated thereafter per the Food and Drug Administration (FDA) approved clevidipine label, to achieve the target SBP +/- 5 mmHg. If the target SBP is achieved at any of the titration doses, that rate may be continued for up to 24 hours. If the desired BP lowering effect is not attained within 30 minutes or not maintained thereafter, any alternative antihypertensive agent may be used per institutional treatment practice, with or without stopping the study drug infusion.

Drug: Stage 1: Clevidipine (double-blinded)

Stage 1: Placebo (double-blinded)

PLACEBO COMPARATOR

Placebo will be administered in a double-blinded fashion intravenously to all patients randomized to the clevidipine arm in Stage 1. Placebo will be initiated at an initial rate of 2 mg/h for the first 1.5 minutes (90 seconds) and titrated thereafter according to the same dosing instructions as for clevidipine to achieve the target SBP +/- 5 mmHg. If the target SBP is achieved at any of the titration doses, that rate may be continued for up to 24 hours. If the desired BP lowering effect is not attained within 30 minutes or not maintained thereafter, any alternative antihypertensive agent may be used per institutional treatment practice, with or without stopping the study drug infusion.

Drug: Stage 1: Placebo (double-blinded)

Stage 2: Clevidipine (open-label)

EXPERIMENTAL

Clevidipine (0.5 mg/mL in 20% lipid emulsion) will be administered in an open-label fashion intravenously to all patients randomized to the clevidipine arm in Stage 2, following the same dosing instructions as in the clevidipine arm in Stage 1. If the desired BP lowering effect is not attained within 30 minutes or not maintained thereafter, any alternative antihypertensive agent may be used per institutional treatment practice, with or without stopping the study drug infusion.

Drug: Stage 2: Clevidipine (open-label)

Stage 2: Standard of Care (open-label)

ACTIVE COMPARATOR

For patients randomized to SOC, the infusion must be continuous, administered per the institution's treatment practice, and dose titration must be performed to a maximum allowed or maximum tolerated dose to achieve target SBP. If treatment with an alternative IV anti-hypertensive agent is required, the patient will be transitioned to an alternative IV antihypertensive agent according to the institutional standard of care.

Drug: Stage 2: Standard of Care (open-label)

Interventions

Stage 1: Clevidipine (double-blinded) DRUG

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.

Also known as: Cleviprex, clevidipine

Stage 1: Clevidipine (double-blinded)

Stage 1: Placebo (double-blinded) DRUG

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.

Also known as: Intralipid

Stage 1: Placebo (double-blinded)

Stage 2: Clevidipine (open-label) DRUG

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.

Also known as: Cleviprex, clevidipine

Stage 2: Clevidipine (open-label)

Stage 2: Standard of Care (open-label) DRUG

Transition to oral antihypertensive medication from SOC IV antihypertensive is per institutional practice.

Stage 2: Standard of Care (open-label)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Medicines Company: lead

Study Sites (9)

Drug Research and Analysis Corporation/Jackson Hospital

Montgomery, Alabama, 36106, United States

Location

University of Arizona Medical Center

Tucson, Arizona, 85719, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

New York Methodist Hospital

Brooklyn, New York, 11215, United States

Location

Maimonides Medical Center

Brooklyn, New York, 11219, United States

Location

Stony Brook University and Medical Center

Stony Brook, New York, 11794, United States

Location

Duke University Hospital

Durham, North Carolina, 27710, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Dyspnea; Hypertension

Interventions

Double-Blind Method; clevidipine; soybean oil, phospholipid emulsion

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health

Study Officials

• William F Peacock, MD, FACEP

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2020
• First Posted: October 19, 2020
• Study Start: August 1, 2014
• Primary Completion: February 1, 2016
• Study Completion: November 1, 2016
• Last Updated: October 19, 2020

Record last verified: 2020-10

Locations

US (9)