Intravenous Vasodilator vs. Inotropic Therapy in Patients With Heart Failure

NCT02767024 | Withdrawn Phase 4 DMC FDA Drug

• 1 other identifier: 2014-3586
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Heart Failure

Outcome Measures

Primary Outcomes (3)

• Arrhythmia incidence

  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

  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

  defined as ≥ 2 consecutive blood pressure measurement with SBP \< 90 mmHg

  within 72 hours after the initiation of the drug

Secondary Outcomes (5)

• ≥2 point improvement in the 5 point Likert dyspnea scale

  within 72 hours after the initiation of the drug involved in the study

• ≥ 30% improvement in the 100 point global patient assessment scale

  within 72 hours after the initiation of the drug involved in the study

• Reduction in the Cardiac Care Unit length of stay

  Up to 30 days

• Reduction in the hospitalization length of stay

  Up to 30 days

• Assessment of difference in restrictive filling pattern by echocardiogram

  from initiation of the of the drug involved in the study up to 72 hours.

Study Arms (2)

Sodium Nitroprusside

EXPERIMENTAL

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; Drug: Furosemide

Dobutamine

ACTIVE COMPARATOR

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: Dobutamine; Drug: Furosemide

Interventions

Sodium nitroprusside DRUG

Sodium nitroprusside is a medication used to lower blood pressure.

Also known as: Generic name for nitropress

Sodium Nitroprusside

Dobutamine DRUG

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.

Dobutamine

Furosemide DRUG

Furosemide is a prescription drug used to treat hypertension (high blood pressure) and edema. Learn about side effects, warnings, dosage, and more.

Also known as: Generic name for Lasix

Dobutamine; Sodium Nitroprusside

Eligibility Criteria

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

You may qualify if:

• 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:
• Persistent dyspnea or orthopnea or edema at screening and at the time or randomization, despite standard background therapy for heart failure.
• Pulmonary congestion on chest radiograph.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Montefiore Medical Center: lead

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10461, United States

Location

Related Publications (13)

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MeSH Terms

Interventions

Nitroprusside; Dobutamine; Furosemide

Intervention Hierarchy (Ancestors)

Ferricyanides; Cyanides; Anions; Ions; Electrolytes; Inorganic Chemicals; Ferric Compounds; Iron Compounds; Hydrogen Cyanide; Nitrogen Compounds; Catecholamines; Amines; Organic Chemicals; Phenethylamines; Ethylamines; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfanilamides; Sulfonamides; Amides; Aniline Compounds; Sulfones; Sulfur Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Cardiology

Study Record Dates

• First Submitted: May 4, 2016
• First Posted: May 10, 2016
• Study Start: May 1, 2018
• Primary Completion: May 1, 2018
• Study Completion: June 1, 2018
• Last Updated: October 31, 2018

Record last verified: 2018-10

Locations

US (1)