Efficacy of Furosemide Versus Vascular Filling in Patients With Acute Myocardial Infarction (FAMIE)

Efficacy of Furosemide Versus Vascular Filling in Patients With Acute Myocardial Infarction With Right Ventricular Extension: A Multicentric Randomized Controlled Trial

Right ventricular necrosis increases patient in hospital mortality and can be observed in 20-50% of patients admitted for during acute myocardial infarction. Current guidelines recommend managing cardiogenic shock related to right ventricular necrosis by optimizing RV load using fluid expansion and if insufficient adding inotropic support. However, several experimental studies reported a potential deleterious effect of right ventricular dilation related to fluid expansion because right and left ventricular interaction decreases stroke volume and cardiac output. Consistently with these finding, a study on a small patient sample conducted at Henri Mondor Hospital demonstrates the safety and efficiency of furosemide in patients with right ventricular necrosis.

The present study is a phase 3, interventional, prospective, randomized, multicenter, double-blind analysis by intention to treat.

The main objective is to demonstrate improved hemodynamic parameters in the short term in patients admitted for acute myocardial infarction with extension RV treated with furosemide.

The primary endpoint is compare the change in cardiac output in patients admitted and treated by either fluid expansion or furosemide.

The study population will consist in 88 patients and the duration of subjects' participation will be one month.

Study Overview

• Status: Unknown
• Conditions: Acute Myocardial Infarction With Right Ventricular Extension
• Intervention / Treatment: Drug: Furosemide; Drug: Placebo filling; Drug: Placebo furosemide; Drug: Vascular filling

• Study Type: Interventional
• Enrollment (Anticipated): 88
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Creteil, France, 94010
    • Henri Mondor Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Age >18 years
• Inferior acute myocardial infarction (≤J + 7)

• Right ventricular extension defined by one following echocardiographic criteria:

  • Dilatation of the right ventricle (RV/LV area> 0.9)
  • RV dysfunction defined by TAPSE <16mm or S velocity <10cm.s-1
  • Akinesia or hypokinesia of two contiguous segments of the right ventricle
  • Decrease of pitch on lung failure flow <150ms

• Inferior vena cava dilatation (≥20mm) and non-compliant (changes <50%) associated with one hemodynamic instability criteria:

  • Oliguria (diuresis <800mL/24h or 0.5mL/kg/min)
  • Systolic blood pressure <100mmHg
  • Oxygen saturation <91% on room air
  • Bradycardia (heart rate <60/min, not valid for patients on beta-blockers).
• Informed consent for study participation signed.

Exclusion Criteria

• Minor and pregnant woman
• Mechanical complications of myocardial infarct
• Patients who received> 40mg diuretic /day during the last 15 days
• Hypersensitivity to furosemide or any of its excipients
• Aortic stenosis (area <1 cm² or mean gradient> 40mmHg), mitral or aortic regurgitation grade ≥3
• Catecholamine support for left ventricular failure with left ventricular ejection fraction <35%
• Renal impairment defined by a serum creatinine> 200μmol / mL
• Sodium and water retention
• Urinary tract obstruction
• Hypovolemia or dehydration
• Severe hypokalemia (K + <3 mmol / L)
• Severe hyponatremia (Na + <125 mmol / L)
• Hepatitis ongoing, liver failure or hepatic encephalopathy
• No affiliation to a social security scheme or other social protection scheme
• Private Patient of liberty or under legal protection (guardianship)
• Inability or refusal to understand or refusal to sign the informed consent from study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Furosemide; Furosemide and Placebo filling (Glucose 5%).	Drug: Furosemide; Furosemide: Special LASILIX (250 mg/25 ml) solution for injection reconditioned glass bottle like "penicillin" of 80mg/8mL. Injection by slow intravenous (1 to 2 minutes per 80mg vial); Other Names: Diuretics, LASILIX.; Drug: Placebo filling; Placebo filling: Glucose 5%, 500mL infused over 30 minutes.; Other Names: G5
Active Comparator: Fluid expansion; Placebo furosemide (Glucose 5%) and Vascular filling The vascular filling is the gold standard in the treatment of acute myocardial infarction	Drug: Placebo furosemide; Placebo furosemide: glucose 5% for injection reconditioned glass bottle like "penicillin" of 80mg/8mL. Injection by slow intravenous (1 to 2 minutes per 80mg vial).; Other Names: G5; Drug: Vascular filling; Vascular filling: Sodium 0.9% 500mL infused over 30 minutes.; Other Names: Fluid expansion, Sodium Chloride NaCl 0.9%.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Improvement in cardiac output (measured by Doppler method) defined by an increase of more than 10% 24 hours after administration of the treatment in patients admitted and treated by either fluid expansion or furosemide.	At Hour 24

Secondary Outcome Measures

Outcome Measure	Time Frame
Intra-hospital mortality	an average of 10 days after inclusion
Rate of inotropic support	an average of 10 days after inclusion
Number of hemodynamic instability requiring fluid expansion	an average of 10 days after inclusion
Change in systolic blood	Hour 24
Change in heart rate	Hour 24
Urine output	Hour 24
The duration of hospitalization in intensive care	an average of month 1
Hospitalizations for cardiovascular reason one month after acute myocardial infarction	month 1
One month mortality	month 1

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Pascal Lim, MD, PhD, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Anticipated): November 1, 2018
• Study Completion (Anticipated): January 1, 2019

Study Registration Dates

• First Submitted: July 31, 2016
• First Submitted That Met QC Criteria: September 16, 2016
• First Posted (Estimate): September 19, 2016

Study Record Updates

• Last Update Posted (Estimate): September 19, 2016
• Last Update Submitted That Met QC Criteria: September 16, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Acute Myocardial Infarction; Diuretic; Right ventricular infarction; Fluid Expansion
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Sodium Potassium Chloride Symporter Inhibitors; Furosemide; Diuretics
• Other Study ID Numbers: P150801

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO