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

NCT ID: NCT01367743

Last Updated: 2019-02-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2016-08-31

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.

Conditions

Cardiogenic Shock

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

epinephrine

Group Type: ACTIVE_COMPARATOR

epinephrine perfusion

Intervention Type: DRUG

perfusion of commercial epinephrine prepared in syringes in order to obtain a MAP of 65-70 mmHg

norepinephrine

Group Type: ACTIVE_COMPARATOR

norepinephrine perfusion

Intervention Type: DRUG

perfusion of commercial norepinephrine prepared in syringes in order to obtain a MAP of 65-70 mmHg

Interventions

epinephrine perfusion

perfusion of commercial epinephrine prepared in syringes in order to obtain a MAP of 65-70 mmHg

Intervention Type: DRUG

norepinephrine perfusion

perfusion of commercial norepinephrine prepared in syringes in order to obtain a MAP of 65-70 mmHg

Intervention Type: DRUG

Other Intervention Names

vasopressor; catecholamine; vasopressor; catecholamine

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Central Hospital, Nancy, France

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philippe VIGNON, Dr

Role: PRINCIPAL_INVESTIGATOR

CHU Limoges

Locations

Nancy Brabois university hospital

Vandœuvre-lès-Nancy, Meurthe Et Moselle, France

CHU de BESANCON / Hôpital Jean Minjoz

Besançon, , France

CHU de DIJON

Dijon, , France

CHU de LIMOGES Hôpital Dupuytren

Limoges, , France

APHM Hôpital NORD

Marseille, , France

Chr Metz Thionville

Metz, , France

CH de MULHOUSE

Mulhouse, , France

AP-HP-Hôpital Cochin

Paris, , France

CHU de STRASBOURG / NHC

Strasbourg, , France

CHU Toulouse

Toulouse, , France

Chru Tours

Tours, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 31472039 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29976291 (View on PubMed)

Study Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2009-017081-23

Identifier Type: -

Identifier Source: org_study_id