Intravenous Vasodilator vs. Inotropic Therapy in Patients With Heart Failure

NCT ID: NCT02767024

Last Updated: 2018-10-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE4

Study Classification

INTERVENTIONAL

Study Start Date

2018-05-01

Study Completion Date

2018-06-01

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Acute Heart Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Sodium nitroprusside

Intervention Type DRUG

Sodium nitroprusside is a medication used to lower blood pressure.

Furosemide

Intervention Type DRUG

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

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.

Group Type ACTIVE_COMPARATOR

Dobutamine

Intervention Type 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.

Furosemide

Intervention Type DRUG

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

Interventions

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Sodium nitroprusside

Sodium nitroprusside is a medication used to lower blood pressure.

Intervention Type 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.

Intervention Type DRUG

Furosemide

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

Intervention Type DRUG

Other Intervention Names

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Generic name for nitropress Generic name for Lasix

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Montefiore Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Mario Garcia

Professor, Cardiology

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Montefiore Medical Center

The Bronx, New York, United States

Site Status

Countries

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United States

References

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WRITING COMMITTEE MEMBERS; Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE Jr, Drazner MH, Fonarow GC, Geraci SA, Horwich T, Januzzi JL, Johnson MR, Kasper EK, Levy WC, Masoudi FA, McBride PE, McMurray JJ, Mitchell JE, Peterson PN, Riegel B, Sam F, Stevenson LW, Tang WH, Tsai EJ, Wilkoff BL; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013 Oct 15;128(16):e240-327. doi: 10.1161/CIR.0b013e31829e8776. Epub 2013 Jun 5. No abstract available.

Reference Type BACKGROUND
PMID: 23741058 (View on PubMed)

Gheorghiade M, Zannad F, Sopko G, Klein L, Pina IL, Konstam MA, Massie BM, Roland E, Targum S, Collins SP, Filippatos G, Tavazzi L; International Working Group on Acute Heart Failure Syndromes. Acute heart failure syndromes: current state and framework for future research. Circulation. 2005 Dec 20;112(25):3958-68. doi: 10.1161/CIRCULATIONAHA.105.590091. No abstract available.

Reference Type BACKGROUND
PMID: 16365214 (View on PubMed)

Heart Failure Society of America; Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA, Givertz MM, Katz SD, Klapholz M, Moser DK, Rogers JG, Starling RC, Stevenson WG, Tang WH, Teerlink JR, Walsh MN. HFSA 2010 Comprehensive Heart Failure Practice Guideline. J Card Fail. 2010 Jun;16(6):e1-194. doi: 10.1016/j.cardfail.2010.04.004.

Reference Type BACKGROUND
PMID: 20610207 (View on PubMed)

Mebazaa A, Nieminen MS, Packer M, Cohen-Solal A, Kleber FX, Pocock SJ, Thakkar R, Padley RJ, Poder P, Kivikko M; SURVIVE Investigators. Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. JAMA. 2007 May 2;297(17):1883-91. doi: 10.1001/jama.297.17.1883.

Reference Type BACKGROUND
PMID: 17473298 (View on PubMed)

Gage J, Rutman H, Lucido D, LeJemtel TH. Additive effects of dobutamine and amrinone on myocardial contractility and ventricular performance in patients with severe heart failure. Circulation. 1986 Aug;74(2):367-73. doi: 10.1161/01.cir.74.2.367.

Reference Type BACKGROUND
PMID: 3731427 (View on PubMed)

Mager G, Klocke RK, Kux A, Hopp HW, Hilger HH. Phosphodiesterase III inhibition or adrenoreceptor stimulation: milrinone as an alternative to dobutamine in the treatment of severe heart failure. Am Heart J. 1991 Jun;121(6 Pt 2):1974-83. doi: 10.1016/0002-8703(91)90834-5.

Reference Type BACKGROUND
PMID: 1852090 (View on PubMed)

Cuffe MS, Califf RM, Adams KF Jr, Benza R, Bourge R, Colucci WS, Massie BM, O'Connor CM, Pina I, Quigg R, Silver MA, Gheorghiade M; Outcomes of a Prospective Trial of Intravenous Milrinone for Exacerbations of Chronic Heart Failure (OPTIME-CHF) Investigators. Short-term intravenous milrinone for acute exacerbation of chronic heart failure: a randomized controlled trial. JAMA. 2002 Mar 27;287(12):1541-7. doi: 10.1001/jama.287.12.1541.

Reference Type BACKGROUND
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Abraham WT, Adams KF, Fonarow GC, Costanzo MR, Berkowitz RL, LeJemtel TH, Cheng ML, Wynne J; ADHERE Scientific Advisory Committee and Investigators; ADHERE Study Group. In-hospital mortality in patients with acute decompensated heart failure requiring intravenous vasoactive medications: an analysis from the Acute Decompensated Heart Failure National Registry (ADHERE). J Am Coll Cardiol. 2005 Jul 5;46(1):57-64. doi: 10.1016/j.jacc.2005.03.051.

Reference Type BACKGROUND
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Elkayam U, Tasissa G, Binanay C, Stevenson LW, Gheorghiade M, Warnica JW, Young JB, Rayburn BK, Rogers JG, DeMarco T, Leier CV. Use and impact of inotropes and vasodilator therapy in hospitalized patients with severe heart failure. Am Heart J. 2007 Jan;153(1):98-104. doi: 10.1016/j.ahj.2006.09.005.

Reference Type BACKGROUND
PMID: 17174645 (View on PubMed)

Grant S, Aitchison T, Henderson E, Christie J, Zare S, McMurray J, Dargie H. A comparison of the reproducibility and the sensitivity to change of visual analogue scales, Borg scales, and Likert scales in normal subjects during submaximal exercise. Chest. 1999 Nov;116(5):1208-17. doi: 10.1378/chest.116.5.1208.

Reference Type BACKGROUND
PMID: 10559077 (View on PubMed)

Allen LA, Metra M, Milo-Cotter O, Filippatos G, Reisin LH, Bensimhon DR, Gronda EG, Colombo P, Felker GM, Cas LD, Kremastinos DT, O'Connor CM, Cotter G, Davison BA, Dittrich HC, Velazquez EJ. Improvements in signs and symptoms during hospitalization for acute heart failure follow different patterns and depend on the measurement scales used: an international, prospective registry to evaluate the evolution of measures of disease severity in acute heart failure (MEASURE-AHF). J Card Fail. 2008 Nov;14(9):777-84. doi: 10.1016/j.cardfail.2008.07.188. Epub 2008 Aug 15.

Reference Type BACKGROUND
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Binanay C, Califf RM, Hasselblad V, O'Connor CM, Shah MR, Sopko G, Stevenson LW, Francis GS, Leier CV, Miller LW; ESCAPE Investigators and ESCAPE Study Coordinators. Evaluation study of congestive heart failure and pulmonary artery catheterization effectiveness: the ESCAPE trial. JAMA. 2005 Oct 5;294(13):1625-33. doi: 10.1001/jama.294.13.1625.

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Mullens W, Abrahams Z, Francis GS, Skouri HN, Starling RC, Young JB, Taylor DO, Tang WH. Sodium nitroprusside for advanced low-output heart failure. J Am Coll Cardiol. 2008 Jul 15;52(3):200-7. doi: 10.1016/j.jacc.2008.02.083.

Reference Type BACKGROUND
PMID: 18617068 (View on PubMed)

Other Identifiers

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2014-3586

Identifier Type: -

Identifier Source: org_study_id

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