Normoxemic Versus Hyperoxemic Extracorporeal Oxygenation in Patients Supported by Veino-arterial ECMO for Cardiogenic Shock (ECMOxy)

Normoxemic Versus Hyperoxemic Extracorporeal Oxygenation : Impact on Organ Dysfunction in Patients Supported by Veino-arterial ECMO for Cardiogenic Shock

Because of dual oxygenation and oxygenator performance (PO2 postoxygenator up to 500 mmHg), hyperoxemia (PaO2 > 150 mmHg) is frequent in veino-arterial ECMO, especially in the lower part of the body, which is mainly oxygenated by ECMO.

By enhancing oxygen free radicals' production, hyperoxemia might favor gut, kidney and liver dysfunction.

We hypothesize that targeting an extracorporeal normoxemia (i.e. PO2 postoxygenator between 100 and 150 mmHg) will decrease gut, kidney and liver dysfunctions, compared to a liberal extracorporeal oxygenation.

Study Overview

• Status: Completed
• Conditions: Extracorporeal Membrane Oxygenation; Cardiogenic Shock
• Intervention / Treatment: Drug: Oxygen gas

Detailed Description

Randomization:

Patients will be randomized in the 6 hours following ECMO start in the normoxemia or in the hyperoxemia group. Randomization will be stratified on center, and medical or postcardiotomy indication for ECMO.

Description of experimental arm (Normoxemia group):

• After randomization, extracorporeal normoxemia is targeted by setting the ECMO membrane oxygen fraction (FmO2) at 60%.
• The objective is to maintain oxygen partial pressure measured on the arterial cannula (PO2 postoxygenator) between 100 and 150 mmHg.
• PO2 postoxygenator is monitored at least twice a day by the nurse.
• If PO2 postoxygenator is less than 100 mmHg or more than 150 mmHg, FmO2 is modified by 10% and PO2 postoxygenator is monitored 10 minutes after.
• Ventilator's settings at let to the clinician's discretion. However, PaO2 on right radial artery will be monitored to ensure that is more that 80 mmHg.
• Intervention will be applied for 7 days after randomization.

Description of the control arm (Hyperoxemia group):

• After randomization, extracorporeal hyperoxemia is targeted by setting the ECMO membrane oxygen fraction (FmO2) at 100%.
• The objective is to maintain PO2 postoxygenator higher than 300 mmHg.
• PO2 postoxygenator is monitored at least twice a day by the nurse.
• If PO2 postoxygenator is less than 300 mmHg, membrane change should be discussed.
• Ventilator's setting at let to the clinician's discretion. However, PaO2 on right radial artery will be monitored to ensure that is more that 80 mmHg.
• Intervention will be applied for 7 days after randomization.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Besancon, France
    • CHU de Besançon

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient supported by veino-arterial ECMO for cardiogenic shock for less than 6 hours
• Affiliation to social protection

Exclusion Criteria:

• Age < 18 years old
• Pregnancy
• Opposition of the patient or his relatives
• Cannulation during cardiopulmonary resuscitation
• Cardiopulmonary resuscitation duration > 10 minutes before ECMO implantation
• Patient moribound on the day of randomization
• Chronic hemodialysis
• Chronic intestinal disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Extracorporeal normoxemia; After randomization, extracorporeal normoxemia is targeted by setting the ECMO membrane oxygen fraction (FmO2) at 60%.; The objective is to maintain oxygen partial pressure measured on the arterial cannula (PO2 postoxygenator) between 100 and 150 mmHg.; PO2 postoxygenator is monitored at least twice a day by the nurse.; If PO2 postoxygenator is less than 100 mmHg or more than 150 mmHg, FmO2 is modified by 10% and PO2 postoxygenator is monitored 10 minutes after.; Ventilator's setting at let to the clinician's discretion. However, PaO2 on right radial artery will be monitored to ensure that is more that 80 mmHg.; Intervention will be applied for 7 days after randomization.	Drug: Oxygen gas; Targeted PO2 postoxygenator is obtained by modulating ECMO Membrane oxygen fraction.
Active Comparator: Extracorporeal hyperoxemia; After randomization, extracorporeal hyperoxemia is targeted by setting the ECMO membrane oxygen fraction (FmO2) at 100%.; The objective is to maintain PO2 postoxygenator higher than 300 mmHg.; PO2 postoxygenator is monitored at least twice a day by the nurse.; If PO2 postoxygenator is less than 300 mmHg, membrane change should be discussed.; Ventilator's setting at let to the clinician's discretion. However, PaO2 on right radial artery will be monitored to ensure that is more that 80 mmHg.; Intervention will be applied for 7 days after randomization.	Drug: Oxygen gas; Targeted PO2 postoxygenator is obtained by modulating ECMO Membrane oxygen fraction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Enterocyte damage	Plasma Intestinal Fatty Acid Biding Protein (I-FABP) concentration	At day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of the oxygenation protocol	Percentage of time in the oxygenation target	From day 0 to day 6
Security of the oxygenation protocol	Number of right radial PaO2 below 80 mmHg	From day 0 to day 6
Organ failure	Death or severe stroke (NIHSS > 11) or mesenteric ischemia	From day 0 to day 30
Organ failure	Non cardiac component of the Sequential Organ Failure Assessment (SOFA) score	At day 0, day 2 and day 6
Organ failure	Plasma lactate concentration	At day 0, day 2 and day 6
Enterocyte damage	Plasma Intestinal Fatty Acid Biding Protein (I-FABP) concentration	At day 0, and day 1
Enterocyte function	Difference between plasma citrulline concentrations at day 0 and day 2	At day 0 and day 2
Liver failure	Plasma Aspartate aminotransferase (ASAT) concentration	At day 0, day 2 and day 6
Liver failure	Prothrombine time	At day 0, day 2 and day 6
Renal failure	Plasma creatinine concentration	At day 0, day 2 and day 6
Renal failure	Need for renal replacement therapy	From 0 to day 6
Systemic inflammation	Plasma CRP, TNF alpha, IL6 and IL8 concentrations	At day 0, day 2 and day 6
Anti-oxydant stock	Plasma vitamin C, vitamin E, and Glutathion concentrations	At day 0, day 2 and day 6

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon

Publications and helpful links

General Publications

• Munshi L, Kiss A, Cypel M, Keshavjee S, Ferguson ND, Fan E. Oxygen Thresholds and Mortality During Extracorporeal Life Support in Adult Patients. Crit Care Med. 2017 Dec;45(12):1997-2005. doi: 10.1097/CCM.0000000000002643.
• Chou HC, Chen CM. Neonatal hyperoxia disrupts the intestinal barrier and impairs intestinal function in rats. Exp Mol Pathol. 2017 Jun;102(3):415-421. doi: 10.1016/j.yexmp.2017.05.006. Epub 2017 May 12.
• Falk L, Sallisalmi M, Lindholm JA, Lindfors M, Frenckner B, Broome M, Broman LM. Differential hypoxemia during venoarterial extracorporeal membrane oxygenation. Perfusion. 2019 Apr;34(1_suppl):22-29. doi: 10.1177/0267659119830513.
• Hayes RA, Shekar K, Fraser JF. Is hyperoxaemia helping or hurting patients during extracorporeal membrane oxygenation? Review of a complex problem. Perfusion. 2013 May;28(3):184-93. doi: 10.1177/0267659112473172. Epub 2013 Jan 15.

Study record dates

Study Major Dates

• Study Start (Actual): January 9, 2022
• Primary Completion (Actual): November 10, 2023
• Study Completion (Actual): December 1, 2023

Study Registration Dates

• First Submitted: July 30, 2021
• First Submitted That Met QC Criteria: July 30, 2021
• First Posted (Actual): August 4, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 27, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Extracorporeal Membrane Oxygenation; Hyperoxia; Cardiogenic shock
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Myocardial Ischemia; Myocardial Infarction; Ischemia; Shock, Cardiogenic; Shock
• Other Study ID Numbers: ECMOxy - pilot study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: 2023
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

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