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Clevidipine vs Placebo or Standard of Care for Dyspnea and Blood Pressure Control in AHF (PRONTO II)

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ClinicalTrials.gov Identifier: NCT04592380
Recruitment Status : Withdrawn (Product was divested to Chiesi USA, who decided to not move forward with study.)
First Posted : October 19, 2020
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
The Medicines Company

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.

Condition or disease Intervention/treatment Phase
Dyspnea Hypertension Acute Heart Failure Drug: Stage 1: Clevidipine (double-blinded) Drug: Stage 1: Placebo (double-blinded) Drug: Stage 2: Clevidipine (open-label) Drug: Stage 2: Standard of Care (open-label) Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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 Start Date : August 2014
Estimated Primary Completion Date : February 2016
Estimated Study Completion Date : November 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Clevidipine

Arm Intervention/treatment
Experimental: Stage 1: Clevidipine (double-blinded)
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)
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.
Other Names:
  • Cleviprex
  • clevidipine

Placebo Comparator: Stage 1: Placebo (double-blinded)
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)
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.
Other Name: Intralipid

Experimental: Stage 2: Clevidipine (open-label)
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)
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.
Other Names:
  • Cleviprex
  • clevidipine

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




Primary Outcome Measures :
  1. Change in dyspnea VAS score from baseline at 3 hours post-baseline [ Time Frame: Immediately prior to study drug administration (baseline) to 3 hours post-baseline ]

Secondary Outcome Measures :
  1. Median time to reach target BP within the first 30 minutes [ Time Frame: Study drug initiation through the first 30 minutes of study drug infusion ]
  2. Percentage of patients who require rescue therapy (ie, receive any alternative IV antihypertensive drug) within the first 30 minutes [ Time Frame: Study drug initiation through the first 30 minutes of study drug infusion ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04592380


Locations
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United States, Alabama
Drug Research and Analysis Corporation/Jackson Hospital
Montgomery, Alabama, United States, 36106
United States, Arizona
University of Arizona Medical Center
Tucson, Arizona, United States, 85719
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
New York Methodist Hospital
Brooklyn, New York, United States, 11215
Maimonides Medical Center
Brooklyn, New York, United States, 11219
Stony Brook University and Medical Center
Stony Brook, New York, United States, 11794
United States, North Carolina
Duke University Hospital
Durham, North Carolina, United States, 27710
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267
United States, Texas
Baylor College of Medicine
Houston, Texas, United States, 77030
Sponsors and Collaborators
The Medicines Company
Investigators
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Principal Investigator: William F Peacock, MD, FACEP Baylor College of Medicine
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Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT04592380    
Other Study ID Numbers: MDCO-CLV-13-03
PRONTO II ( Other Identifier: The Medicines Company (Sponsor) )
First Posted: October 19, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
Additional relevant MeSH terms:
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Dyspnea
Heart Failure
Cardiovascular Diseases
Heart Diseases
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Clevidipine
Soybean oil, phospholipid emulsion
Fat Emulsions, Intravenous
Parenteral Nutrition Solutions
Pharmaceutical Solutions
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Calcium-Regulating Hormones and Agents
Physiological Effects of Drugs