Impact of Adrenoreceptor Expressions on Inflammatory Pattern in Refractory Cardiogenic Shock Under VA ECMO (ADRECMO)

Impact of Adrenoreceptor Expressions on Inflammatory Pattern in Refractory Cardiogenic Shock Patients Treated by Veno-arterial Extra-Corporeal Membrane Oxygenation

Refractory cardiogenic shock is characterized by a decreased in cardiac output with hypo-responsiveness to increasing doses of catecholamines resulting in a profound tissular ischemia. VAECMO, by restoring a circulatory flow, could be associated to a major reperfusion syndrome which may lead some patients to multiple organ failures and death. Pathophysiology of this syndrome includes 1/an hyper-adrenergic state secondary to the over activation of the sympathetic system and 2/ a major release of pro-inflammatory cytokines. As adrenoreceptors are also exhibited on immunes cells, the pro-inflammatory state might be enhanced by the over-activation of the sympathetic system.

Study Overview

• Status: Completed
• Conditions: Inflammation; Autonomic Nervous System Diseases; Shock, Cardiogenic; Extra-Corporeal-Life-Support ( ECLS)
• Intervention / Treatment: Diagnostic test: Biological

Detailed Description

NB : A repartition according to other ongoing study (HYPOECMO NCTNCT02754193) is planned

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Antoine Kimmoun, MD; Phone Number: 0033383154079; Email: a.kimmoun@chru-nancy.fr

Study Locations

• France
  • Nancy, France, 54000
    • CHRU Nancy

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patients in ICU

• Refractory cardiogenic shock

  • Cardiogenic shock: Systolic Arterial Pressure <90mmHg, or Mean Arterial Pressure <65mmHg, adequate volemia, peripheral hypoperfusion symptoms, cardiac index < 2.2 l/min/m2)
  • Refractory state: hypo responsiveness to norepinephrine AND/OR persisting profound hypo perfusion clinical symptoms despite optimal resuscitation
• needing an Extra-Corporeal-Life-Support
• informed consent from relatives or patient
• Affiliation to a social security regimen
• Preliminary medical examination

Exclusion Criteria:

• Patients under ECLS for a/an :

  • Cardiotoxic poisoning
• Human immunodeficient Virus or Viral hepatitis C
• Patient < 18 yo
• Pregnancy
• Patient under protective supervision

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Refractory cardiogenic shock under ECLS

Diagnostic test: Biological; We will assess in all patients under ECLS for the treatment of a cardiogenic shock at day 0 (ECLS initiation) day 3 and day "ECLS weaning" : Biological assessment: Adrenoreceptors α1, α2, β1, β2, β3 on monocytes and lymphocytes T helper by flow cytometry; Lymphocytes Th1/Th2 pattern by flow cytometry; Cytokines on plasma : Interleukin (IL) 4, IL 12, TNF α, INF γ , IL1, IL6, IL10 Clinical assessment: Hemodynamic parameters; Cumulated doses of catecholamines; Cardiac output variation measured by echocardiography during a standardized weaning procedure of ECLS at a constant mean arterial pressure (only on day 3 and Day "ECLS weaning")

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cytokines (plasma TNF α, INF γ, IL4, IL 12, IL1 IL 6 IL 10)	Exposition variable will be the density of α1, α2, β1, β2, β3-adrenoreceptors on immune cells (monocytes and lymphocytes T helper)	day 0 (ECLS initiation), day 3, day "ECLS weaning"

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in hemodynamic parameters	Arterial pressures	day 0 (ECLS initiation), day 3, day "ECLS weaning"
Change in hemodynamic parameters	heart rate	day 0 (ECLS initiation), day 3, day "ECLS weaning"
Change in hemodynamic parameters	cumulated doses of catecholamines	day 0 (ECLS initiation), day 3, day "ECLS weaning"
Cardiac output variation during a weaning ECLS procedure	At a constant mean arterial pressure (65-75 mmHg), measurement by echocardiography of cardiac output at 2 times: baseline (3L/min of ECLS flow); after 45 min at weaning output (1.5 L/min of ECLS flow) Variation of norepinephrine doses will be also recorded	day 3, day "ECLS weaning"
Mortality		28 days and 90 days
Change in TH1 and TH2 pattern	Assessment in CD3/CD4 + cells of INF γ; IL12 (TH1) and IL4 (TH2)	day 0 (ECLS initation), day 3, day "ECLS weaning"

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France
• Investigators: Principal Investigator: Antoine Kimmoun, MD, CHRU Nancy

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2017
• Primary Completion (Actual): May 24, 2022
• Study Completion (Actual): May 24, 2022

Study Registration Dates

• First Submitted: September 21, 2017
• First Submitted That Met QC Criteria: October 26, 2017
• First Posted (Actual): October 31, 2017

Study Record Updates

• Last Update Posted (Actual): April 19, 2023
• Last Update Submitted That Met QC Criteria: April 15, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: inflammation; Cardiogenic shock; Extra-Corporeal-Life-Support (ECLS); adrenergic system
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Inflammation; Shock; Nervous System Diseases; Shock, Cardiogenic; Primary Dysautonomias; Autonomic Nervous System Diseases
• Other Study ID Numbers: 2016-A00707-44

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No