Clevidipine in the Treatment of Blood Pressure in Patients With Acute Heart Failure (PRONTO)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
The Medicines Company
ClinicalTrials.gov Identifier:
NCT00803634
First received: December 3, 2008
Last updated: June 6, 2012
Last verified: June 2012
  Purpose

The purpose of this study is 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.


Condition Intervention Phase
Hypertension
Heart Failure
Drug: Clevidipine butyrate injectable emulsion
Drug: standard of care IV antihypertensive treatment
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Safety and Efficacy Study of Blood Pressure Control in Acute Heart Failure - A Pilot Study (PRONTO)

Resource links provided by NLM:


Further study details as provided by The Medicines Company:

Primary Outcome Measures:
  • Median time and percent of patients that attain the initial prespecified SBP target range (minimum of 20 mm Hg and a maximum of 40 mm Hg apart) and a 15% reduction in SBP from baseline within the first 30 minutes [ Time Frame: Within initial 30-minute treatment period ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • The percentage of patients who reach the prespecified SBP target range without falling below the lower limit of the prespecified target range during the first 30 minute treatment period [ Time Frame: First 30-minute treatment period ] [ Designated as safety issue: No ]
  • Magnitude and duration of SBP excursions (calculated as area under the curve) outside the target range(s) normalized per hour for the duration of the study drug administration up to 96 hours [ Time Frame: Duration of study drug administration up to 96 hours ] [ Designated as safety issue: No ]
  • The percentage of patients in whom the SBP falls below the lower limit of the prespecified target range at any time during the first 30 minutes and below the target range at any time during the entire study drug treatment period up to 96 hours [ Time Frame: Study drug treatment period, up to 96 hours ] [ Designated as safety issue: No ]
  • Change from baseline in the dyspnea scores (Visual Analogue Score, Vasodilatation in the Management of Acute Congestive Heart Failure, and Provocative Dyspnea Assessment) at each time point [ Time Frame: Up to 1 hour post-termination of study drug treatment ] [ Designated as safety issue: No ]
  • Length of time on study drug without using any other concomitant IV antihypertensive agent up to 96 hours [ Time Frame: Up to 96 hours ] [ Designated as safety issue: No ]
  • Percentage of patients who receive any alternative IV antihypertensive drug at any time during the study drug treatment period up to 96 hours [ Time Frame: Up to 96 hours ] [ Designated as safety issue: No ]
  • Number of episodes and percent time the SBP < 90 mm Hg during study drug administration up to 96 hours [ Time Frame: Up to 96 hours ] [ Designated as safety issue: No ]
  • Number of patients that require intubation during study drug administration up to 96 hours [ Time Frame: Up to 96 hours ] [ Designated as safety issue: No ]
  • Safety of a prolonged infusion of study drug assessed according to clinical laboratory parameters, and adverse events and SAEs up to 7 days or discharge whichever occurs first and SAEs through 30 days from randomization into the study [ Time Frame: AEs will be assessed up to 7 days or discharge, whichever occurs first following randomization. SAEs will be assessed for 30 days following randomization. ] [ Designated as safety issue: Yes ]

Enrollment: 117
Study Start Date: December 2008
Study Completion Date: April 2012
Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clevidipine butyrate injectable emulsion Drug: Clevidipine butyrate injectable emulsion
Clevidipine (0.5 mg/mL in 20% lipid emulsion; 100 mL bottles) will be administered intravenously via a single dedicated line to all patients randomized to receive clevidipine. Clevidipine will be infused at an initial rate of 2 mg/h for the first 3 min. Thereafter, titration to effect is to proceed by doubling the dose every 3 min, up to a maximum of 32 mg/h, until the desired effect (SBP within the target range) is attained. Clevidipine will be administered for a minimum of 30 min and a maximum duration of 96 h.
Other Name: Cleviprex
Active Comparator: standard of care IV antihypertensive treatment Drug: standard of care IV antihypertensive treatment
For patients randomized to standard of care (SOC) IV antihypertensive treatment, the selection of treatment is at the discretion of the investigator. Infusion must be administered per the institution's treatment practice and dose titration performed to a maximum allowed or tolerated dose to achieve SBP control. SOC IV antihypertensive agent will be administered for a minimum of 30 min and, if medically warranted, may continue beyond 96 hours at the investigator's discretion.

Detailed Description:

This study will be an open-label randomized efficacy and safety pilot trial in patients with acute heart failure and hypertension (SBP ≥160 mm Hg) requiring parenteral antihypertensive therapy. The study will include 3 separate periods: Screening Period, Treatment Period (up to 96 h) and Follow-up Period (up to 30 days post-randomization) representing approximately a maximum of 30 days on study.

Eligible patients will be randomized to receive clevidipine or SOC IV antihypertensive treatment (study drug) in an open-label manner in a ratio of 1:1. At the time of randomization, a prespecified target SBP range will be recorded. Clevidipine will be infused at an initial rate of 2 mg/h for the first 3 min. Thereafter, titration to higher infusion rates can be attempted as needed to obtain the prespecified target SBP range. Titration to effect is to proceed by doubling the dose every 3 min, up to a maximum of 32 mg/h, until the desired effect (SBP within the prespecified target range) is attained. SOC IV antihypertensive treatment will be administered per the institution's treatment practice.

During the initial 30 min of the treatment period, clevidipine or SOC IV antihypertensive treatment should be administered as monotherapy until 30 min post-initiation of study drug. The use of an alternative antihypertensive agent(s) or changing the SBP target range is discouraged and limited to where medically necessary to maintain patient safety. Clevidipine may continue for a maximum of 96 hours. If medically warranted, SOC IV antihypertensive treatment may continue beyond 96 hours at the investigator's discretion.

A Data Safety Monitoring Board will be utilized periodically throughout the study to monitor the safety of patients. AEs will continue to be assessed for 7 days or discharge whichever occurs first following randomization. SAEs will be assessed for 30 days following randomization. Subjects will be contacted by telephone or in person to determine if any SAEs have occurred following study drug treatment and to follow up on Heath Economic assessments. Up to 5 additional days will be allowed to complete this final assessment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 (before starting study drug) of ≥160 mm Hg
  • Dyspnea score (sitting) of at least 5 on a 10 cm visual analog scale
  • Requires IV antihypertensive therapy to lower BP
  • 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, and bi-level positive airway pressure are 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00803634

Locations
United States, Alabama
Norman Garrison
Montgomery, Alabama, United States, 36106
United States, California
Centinela Hospital
Inglewood, California, United States, 90301
United States, Louisiana
Louisiana State University Health Sciences Center
Baton Rouge, Louisiana, United States, 70805
Louisiana State University Health Sciences Center - Emergency Medicine
New Orleans, Louisiana, United States, 70112
United States, Michigan
William Beaumont Hospital
Royal Oak, Michigan, United States, 48073
William Beaumont-Troy
Troy, Michigan, United States, 48085
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
United States, New York
Stony Brook University and Medical Center
Stony Brook, New York, United States, 11794
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267
MetroHealth Medcial Center
Cleveland, Ohio, United States, 44109
The Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Tennessee
Vanderbilt University Medical Center
Nashville, Tennessee, United States, 37232-4700
France
Centre hospitalier de Pontoise René Dubos
CERGY PONTOISE Cedex, France, 95303
Germany
Charité - Universitätsmedizin Berlin
Berlin, Germany, 13353
Switzerland
Cardiocentro Ticino
Lugano, Switzerland, CH-6900
Sponsors and Collaborators
The Medicines Company
Investigators
Principal Investigator: W. Frank Peacock, MD The Cleveland Clinic
  More Information

No publications provided

Responsible Party: The Medicines Company
ClinicalTrials.gov Identifier: NCT00803634     History of Changes
Other Study ID Numbers: TMC-CLV-08-01
Study First Received: December 3, 2008
Last Updated: June 6, 2012
Health Authority: United States: Food and Drug Administration
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Switzerland: Swissmedic

Keywords provided by The Medicines Company:
Hypertension
Antihypertensive Agent
Calcium Channel Blocker

Additional relevant MeSH terms:
Heart Failure
Hypertension
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Antihypertensive Agents
Calcium Channel Blockers
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014