Intravenous Vasodilator vs. Inotropic Therapy in Patients With Heart Failure (PRIORITY-ADHF)

October 29, 2018 updated by: Mario Garcia, Montefiore Medical Center

Intravenous Vasodilator vs. Inotropic Therapy in Patients With Heart Failure Reduced Ejection Fraction and Acute Decompensation With Low Cardiac Output: A Single Center, Randomized, Non-Blinded, and Parallel Study (PRIORITY-ADHF Study)

Single center, prospective, randomized, non-blinded research study comparing intravenous vasodilator infusion vs. inotropic infusion in patients admitted to the hospital or in the emergency room at Montefiore Medical Center presenting with the diagnosis of acute decompensated systolic heart failure with low cardiac output but no hypotensive.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

The objective of the study is determine if the administration of diuretics with intravenous sodium nitroprusside (vasodilator therapy) in comparison to intravenous dobutamine (inotropic therapy) will lead to a reduction in the primary and secondary endpoints in patients with acute decompensated systolic heart failure with low cardiac output and no hypotensive.

Study Type

Interventional

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • Bronx, New York, United States, 10461
        • Montefiore Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • History of heart failure reduced ejection fraction (HFrEF), New York Heart Association (NYHA) class IV and known left ventricular ejection fraction (LVEF ) ≤ 40% within the last 6 months by any of the following imaging techniques: echocardiogram, radio-nuclear stress test, ventriculogram or cardiac magnetic resonance imaging (CMR) performed within 6 months.

  • Hospitalized or presented to the emergency department for acute decompensated heart failure (ADHF) with the anticipated requirement if intravenous (IV) therapy (including IV diuretics). ADHF is defined as including all of the following measured at any time between the presentation (including the emergency department) and the end of the screening:

    1. Persistent dyspnea or orthopnea or edema at screening and at the time or randomization, despite standard background therapy for heart failure.
    2. Pulmonary congestion on chest radiograph.
    3. N-terminal pro b-type natriuretic peptide (NT-proBNP) ≥ 2000 pg/ml; for patients ≥ 75 years old or with current atrial fibrillation, NT-proBNP ≥ 3000 pg/ml.
  • Clinical suspicious of low cardiac output state; consider by the presence of any of the following signs or symptoms of hypoperfusion: narrow pulse pressure, cold extremities, mental obtundation, declining renal function, and/or low serum sodium.
  • Systolic blood pressure (SBP) measured ≥ 90 but < 120 mmHg at the start and the end of the screening, without use of an intravenous vasopressor therapy.
  • Hemodynamic criteria: CI ≤ 2.2 L·min-1·m-2 based on CO calculated by Fick formula and PCWP ≥ 20 mmHg measured by right heart catheterization at the time of the enrollment and confirmed by Swan-Ganz measurement upon arrival to the Cardiac Care Unit (CCU).
  • Able to be randomized within the first 24 hours from the presentation to the hospital, including the emergency department.

Exclusion Criteria:

  • Clinical evidence of acute coronary syndrome (ACS) currently or within 30 days prior to enrollment. (Note that the diagnosis of ACS is a clinical diagnosis and that the sole presence of elevated troponin concentrations is not sufficient for a diagnosis of ACS).
  • Significant, uncorrected left ventricular outflow track obstruction, such us obstructive cardiomyopathy or severe aortic stenosis (i.e. aortic valve area < 1.0 cm2 or mean gradient > 40 mmHg on prior or current echocardiogram).
  • Severe mitral stenosis.
  • Severe aortic insufficiency or severe mitral regurgitation for which surgical or percutaneous intervention is indicated.
  • Documented, prior to or at the time of the randomization, restrictive amyloid myocardiopathy or acute myocarditis or hypertrophic obstructive, restrictive or constrictive cardiomyopathy (does not include restrictive mitral filling patterns seen on Doppler echocardiographic assessments of diastolic function).
  • Complex congenital heart disease.
  • Significant arrhythmias, which include any of the following: sustained ventricular tachycardia; atrial fibrillation or atrial flutter with sustained heart rate > 130 beats per minute.
  • Bradycardia with sustained ventricular rate < 45 beats per minute.
  • Temperature > 38.5°C (oral or equivalent) or sepsis or active infection requiring IV anti-microbial treatment.
  • History of malignancy (other than localized basal cell carcinoma of the skin), treated or untreated or any terminal illness (other than heart failure) with a current life expectancy less than a year.
  • Major surgery or major neurologic event including cerebrovascular events, within 30 days prior to enrollment.
  • Need for mechanical circulatory support (MCS), including intra-aortic balloon pump, Extracorporeal Membrane Oxygenation (ECMO) or any ventricular assist device.
  • Need for mechanical ventilatory support (endotracheal intubation or mechanical ventilation).
  • Patient with chronic heart failure and inotropic-depended.
  • Current (within 2 hours prior to screening) treatment with any IV vasoactive therapies, including vasodilators, inotropic agents and vasopressors.
  • Patients with severe renal impairment defined as pre-randomization estimated Glomerular Filtration Rate (eGFR) < 25 ml/min/1.73m2 calculated using the simplified Modification of Diet in Renal Disease (sMDRD) equalization and/or those receiving current or planned dialysis or ultrafiltration.
  • Patients with acute kidney injury defined as an increase in serum creatinine 3 times of baseline, or reduction in urine output to <0.3 mL/kg per hour for ≥12 hours, or anuria for ≥12 hours, or patients undergoing renal replacement therapy.
  • Patients with Child C cirrhosis or history of cirrhosis with evidence of portal hypertension such as varices.
  • Patients with acute liver failure and serum transaminase: aspartate transaminase (AST) and/or alanine transaminase (ALT) > 3 times above the upper limit of normal.
  • Any major solid organ transplant recipient or planned/anticipated organ transplant within 1 year.
  • Patients with hematocrit < 25%, or a history of blood transfusion within 14 days prior to screening, or active life-threatening gastrointestinal bleeding.
  • Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin (hCG) laboratory test. .
  • History of hypersensitive to dobutamine or sodium nitroprusside.
  • Inability to follow instructions or comply with follow-up procedures.
  • Any other medical condition (s) that the investigator deems unsuitable for the study, including drug or alcohol use or psychiatric, behavioral or cognitive disorder.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Sodium Nitroprusside
Dose titration will start at 25 μg/min and increased by 25 μg every 5 minutes to maximal dose of 400 μg/min while maintaining SBP ≥ 90 mmHg. Every 5 minutes, the Pulmonary Capillary Wedge Pressure (PCWP), SBP will be measured. If PCWP > 16 mmHg while maintaining SBP ≥ 90 mmHg, the investigator will proceed to titrate dose with the goal to achieve the target of PCWP ≤ 16 mmHg and Cardiac Index (CI) > 2.2 L·min-1·m-2, or maximal infusion dose has been reached, whichever comes earliest. Continuous intravenous furosemide infusion dose will be maintained by protocol.
Drug: Sodium nitroprusside
Sodium nitroprusside is a medication used to lower blood pressure.
Other Names:
  • Generic name for nitropress
Drug: Furosemide
Furosemide is a prescription drug used to treat hypertension (high blood pressure) and edema. Learn about side effects, warnings, dosage, and more.
Other Names:
  • Generic name for Lasix
Active Comparator: Dobutamine
Dose titration will start at 2.5 μg/kg/min and increased to doses of 5, 7.5 and 10 μg/kg/min (maximal dose). Every 30 minutes, the investigator will collect Pulmonary Artery (PA) blood samples for PA sat measurement to calculate Cardiac Output (CO) and CI by Fick. If CI ≤ 2.2 L·min-1·m-2, the investigator will proceed to titrate dose until CI > 2.2 L·min-1·m-2 or maximal infusion dose has been reached, whichever comes earliest. Continuous intravenous furosemide infusion dose will be maintained by protocol.
Drug: Furosemide
Furosemide is a prescription drug used to treat hypertension (high blood pressure) and edema. Learn about side effects, warnings, dosage, and more.
Other Names:
  • Generic name for Lasix
Drug: Dobutamine
Dobutamine is a direct-acting inotropic agent whose primary activity results from stimulation of the ß receptors of the heart while producing comparatively mild chronotropic, hypertensive, arrhythmogenic, and vasodilative effects.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Arrhythmia incidence
Time Frame: within 72 hours after the initiation of the drug
defined by the presence of ventricular arrhythmia (either ventricular tachycardia or ventricular fibrillation) or supraventricular arrhythmias (either recurrent or new onset of atrial fibrillation, atrial flutter or supraventricular tachycardia) with sustained heart rate ≥ 130 beats per minute
within 72 hours after the initiation of the drug
Serum troponin T release
Time Frame: within 72 hours after the initiation of the drug
defined as measured serum cardiac troponin T (cTnT) with a value > 0.10 ng/ml
within 72 hours after the initiation of the drug
Hypotension incidence
Time Frame: within 72 hours after the initiation of the drug
defined as ≥ 2 consecutive blood pressure measurement with SBP < 90 mmHg
within 72 hours after the initiation of the drug

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
≥2 point improvement in the 5 point Likert dyspnea scale
Time Frame: within 72 hours after the initiation of the drug involved in the study
within 72 hours after the initiation of the drug involved in the study
≥ 30% improvement in the 100 point global patient assessment scale
Time Frame: within 72 hours after the initiation of the drug involved in the study
within 72 hours after the initiation of the drug involved in the study
Reduction in the Cardiac Care Unit length of stay
Time Frame: Up to 30 days
Length of stay (in hours) will be defined as the index discharge date and time minus the initiation of study drug date and time.
Up to 30 days
Reduction in the hospitalization length of stay
Time Frame: Up to 30 days
Length of stay (in hours) will be defined as the index discharge date and time minus the initiation of study drug date and time.
Up to 30 days
Assessment of difference in restrictive filling pattern by echocardiogram
Time Frame: from initiation of the of the drug involved in the study up to 72 hours.
from initiation of the of the drug involved in the study up to 72 hours.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Montefiore Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2018

Primary Completion (Actual)

May 1, 2018

Study Completion (Actual)

June 1, 2018

Study Registration Dates

First Submitted

May 4, 2016

First Submitted That Met QC Criteria

May 6, 2016

First Posted (Estimate)

May 10, 2016

Study Record Updates

Last Update Posted (Actual)

October 31, 2018

Last Update Submitted That Met QC Criteria

October 29, 2018

Last Verified

October 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2014-3586

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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