Study Comparing the Efficacy and Tolerability of Epinephrine and Norepinephrine in Cardiogenic Shock (OptimaCC)

Optimizing the Use of Vasopressor After Coronary Reperfusion in Cardiogenic Shock Secondary to Myocardial Infarction. Pathophysiological Study Comparing the Efficacy and Cardio-circulatory Tolerability of Epinephrine and Norepinephrine

The efficacy and tolerability of norepinephrine and epinephrine in cardiogenic shock after reperfused myocardial infarction will be compared, by following cardiac index evolution as main criteria. The study is a pilot pathophysiological study, randomized, double blind and multicenter.

Study Overview

• Status: Completed
• Conditions: Cardiogenic Shock
• Intervention / Treatment: Drug: epinephrine perfusion; Drug: norepinephrine perfusion

Detailed Description

Cardiogenic shock secondary to myocardial infarction is a frequent pathology in reanimation and is associated with high mortality (50%). Hemodynamic management and notably the choice of vasopressor in cardiogenic shock states secondary to myocardial infarction (cardiac index < 2.2 l/min/m-2) is not codified. There are two opposite views: a) the first is based on the fact that an hypotensive patient with low cardiac output is primarily in need of an inotropic agent and that, consequently, epinephrine is the molecule of choice (inotropic and vasoconstrictor); b) the second is based on the fact that hypotension also reflects a certain degree of vascular failure and vascular vasoplegia and therefore norepinephrine is the molecule of choice along with, if needed, the eventual addition of dobutamine in order to separately titrate vasoconstriction and inotropism.

Study hypotheses: epinephrine could facilitate myocardial function by providing the latter with its preferred substrate (lactate) and thus induce a higher cardiac index along with increased energy expenditure. Norepinephrine is the therapy of choice of hypotensive states; nevertheless its lack of inotropic effect could theoretically exacerbate myocardial failure. Thus, the aim of the study is to compared the efficiency and the tolerability of norepinephrine and epinephrine in cardiogenic shock after reperfused myocardial infarction.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Besancon, France, 25030
    • CHU de BESANCON / Hôpital Jean Minjoz
  • Dijon, France, 21079
    • CHU de Dijon
  • Limoges, France, 87042
    • CHU de Limoges Hopital Dupuytren
  • Marseille, France, 13015
    • APHM Hôpital Nord
  • Metz, France, 57000
    • CHR Metz Thionville
  • Mulhouse, France, 68070
    • CH de Mulhouse
  • Paris, France, 75014
    • Ap-Hp-Hopital Cochin
  • Strasbourg, France, 67091
    • CHU de STRASBOURG / NHC
  • Toulouse, France
    • CHU Toulouse
  • Tours, France, 37044
    • CHRU TOURS
  • Meurthe Et Moselle
    • Vandoeuvre les Nancy, Meurthe Et Moselle, France, 54500
      • Nancy Brabois university hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• man or woman older than 18 years
• cardiogenic shock due to myocardial infarction treated by angioplasty
• SAP < 90 MM Hg or MAP < 65 mm Hg without vasopressor or vasopressor necessity
• sign of tissue hypoperfusion
• cardiac index < 2.2 l/mn/m2 in the absence of vasopressive or inotropic therapy
• pulmonary artery occlusion pressure > 15 mmHg or echocardiographic evidence of high pressure (mitral profile)
• exclusion of covert hypovolemia : Delta PP if feasible should be > 13% (patient adapted to the ventilator and sinus rhythm) and /or no response to passive leg raising
• ejection fraction < 40% in ultrasound without inotrope support. This criteria will not be taken into account in instances of treatment with dopamine, norepinephrine, epinephrine, dobutamine or milrinone.

Exclusion Criteria:

• shock of other origin
• immediate indications for mechanical assistance device
• minor aged patients
• patients for whom written consent - by patient or family - has not been obtained. Given the seriousness of the medical situation at the time of inclusion, patient consent will be difficult if not impossible to obtain. The inclusion will only be possible after information is provided and consent is obtained from a family member. As soon as possible, protocol information will be issued to the patient in order to obtain consent for continuance.
• cardiac arrest with early signs of cerebral anoxia.
• septic, toxic and obstructive cardiomyopathy
• arrhythmogenic cardiomyopathy
• patient with coronary insufficiency
• patient with ventricular rhythm disorders
• patient treated with a medicine listed in contre indication
• patient without social assurance
• patient major under legal protection or safeguard justice

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
Active Comparator: epinephrine	Drug: epinephrine perfusion; perfusion of commercial epinephrine prepared in syringes in order to obtain a MAP of 65-70 mmHg; Other Names: vasopressor; catecholamine
Active Comparator: norepinephrine	Drug: norepinephrine perfusion; perfusion of commercial norepinephrine prepared in syringes in order to obtain a MAP of 65-70 mmHg; Other Names: vasopressor; catecholamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compared effects of investigated drugs on cardiac index	effectiveness of the treatment assessed by the evolution of cardiac index	H0; H2, H4, H6, H12, H24, H48 and H72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
pro/anti-inflammatory cytokines	Compared effects of investigated drugs on pro/anti-inflammatory cytokines	H0, H24, H48 and H72
BNP	Compared effects of investigated drugs on BNP	H0, H24, H48 and H72
Troponin	Compared effects of investigated drugs on Troponin	H0, H24, H48 and H72
catecholamine doses	Compared effects of investigated drugs on the catecholamine doses	H0, H24, H48 and H72
organ failure (SOFA Score)	Compared effects of investigated drugs on the organ failure	H0, H24, H48 and H72
Lactate clearance	Compared effects of investigated drugs on the Lactate clearance	H0, H2, H6, H12, H24 and H48
heart rate	Compared effects of investigated drugs on heart rate and the incidence of arrhythmia	H0, H2, H4, H6, H12, H24, H48 and H72
cardiac power index	Compared effects of investigated drugs on cardiac power	H0, H2, H4, H6, H12, H24, H48 and H72.
SVO2	Compared effects of investigated drugs on the SVO2	H0, H2, H4, H6, H12, H24, H48 and H72.
cardiac double product	Compared effects of investigated drugs on the cardiac double product	H0, H2, H4, H6, H12, H24, H48 and H72.
refractory cardiogenic shock	compared effects of the investigated drugs on the occurrence of refractory cardiogenic shock	H0, H2, H4, H6, H12, H24, H48 and H72.

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Investigators: Principal Investigator: Philippe VIGNON, Dr, CHU Limoges

Publications and helpful links

General Publications

• Takagi K, Blet A, Levy B, Deniau B, Azibani F, Feliot E, Bergmann A, Santos K, Hartmann O, Gayat E, Mebazaa A, Kimmoun A. Circulating dipeptidyl peptidase 3 and alteration in haemodynamics in cardiogenic shock: results from the OptimaCC trial. Eur J Heart Fail. 2020 Feb;22(2):279-286. doi: 10.1002/ejhf.1600. Epub 2019 Aug 31.
• Levy B, Clere-Jehl R, Legras A, Morichau-Beauchant T, Leone M, Frederique G, Quenot JP, Kimmoun A, Cariou A, Lassus J, Harjola VP, Meziani F, Louis G, Rossignol P, Duarte K, Girerd N, Mebazaa A, Vignon P; Collaborators. Epinephrine Versus Norepinephrine for Cardiogenic Shock After Acute Myocardial Infarction. J Am Coll Cardiol. 2018 Jul 10;72(2):173-182. doi: 10.1016/j.jacc.2018.04.051.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (Actual): February 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: May 10, 2011
• First Submitted That Met QC Criteria: June 6, 2011
• First Posted (Estimate): June 7, 2011

Study Record Updates

• Last Update Posted (Actual): February 1, 2019
• Last Update Submitted That Met QC Criteria: January 30, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: myocardial infarction; norepinephrine; epinephrine; cardiac output
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Shock; Shock, Cardiogenic; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-Agonists; Sympathomimetics; Mydriatics; Norepinephrine; Epinephrine; Vasoconstrictor Agents
• Other Study ID Numbers: 2009-017081-23

Plan for Individual participant data (IPD)

Study Data/Documents

1. Statistical Analysis Plan