Clinical trial NCT01367743: Study Comparing the Efficacy and Tolerability of Epinephrine and Norepinephrine in Cardiogenic Shock
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Cardiogenic Shock
Keywords: myocardial infarction
epinephrine
norepinephrine
cardiac output
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
First posted: 2011-06-07
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Compared effects of investigated drugs on cardiac index
timeFrame: H0; H2, H4, H6, H12, H24, H48 and H72
Secondary outcomes:
measure: pro/anti-inflammatory cytokines
timeFrame: H0, H24, H48 and H72
measure: BNP
timeFrame: H0, H24, H48 and H72
measure: Troponin
timeFrame: H0, H24, H48 and H72
measure: catecholamine doses
timeFrame: H0, H24, H48 and H72
measure: organ failure (SOFA Score)
timeFrame: H0, H24, H48 and H72
measure: Lactate clearance
timeFrame: H0, H2, H6, H12, H24 and H48
measure: heart rate
timeFrame: H0, H2, H4, H6, H12, H24, H48 and H72
measure: cardiac power index
timeFrame: H0, H2, H4, H6, H12, H24, H48 and H72.
measure: SVO2
timeFrame: H0, H2, H4, H6, H12, H24, H48 and H72.
measure: cardiac double product
timeFrame: H0, H2, H4, H6, H12, H24, H48 and H72.
measure: refractory cardiogenic shock
timeFrame: H0, H2, H4, H6, H12, H24, H48 and H72.
Other outcomes:
Locations:
city: Vandoeuvre les Nancy
country: France
facility: Nancy Brabois university hospital
state: Meurthe Et Moselle
city: Besancon
country: France
facility: CHU de BESANCON / Hôpital Jean Minjoz
city: Dijon
country: France
facility: CHU de DIJON
city: Limoges
country: France
facility: CHU de LIMOGES Hôpital Dupuytren
city: Marseille
country: France
facility: APHM Hôpital NORD
city: Metz
country: France
facility: Chr Metz Thionville
city: Mulhouse
country: France
facility: CH de MULHOUSE
city: Paris
country: France
facility: AP-HP-Hôpital Cochin
city: Strasbourg
country: France
facility: CHU de STRASBOURG / NHC
city: Toulouse
country: France
facility: CHU Toulouse
city: Tours
country: France
facility: Chru Tours
Study officials:
affiliation: CHU Limoges
name: Philippe VIGNON, Dr
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.