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

Cardiogenic Shock Clinical Trial

— ECMOxy  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04990349
• Other study ID #: ECMOxy - pilot study
• Status: Recruiting
• Phase: Phase 3
• Start date: January 9, 2022
• Est. completion date: July 9, 2024

Study information

• Verified date: September 2023
• Source: Centre Hospitalier Universitaire de Besancon
• Contact: Hadrien Winiszewski, MD
• Phone: 03 81 66 81 27
• Email: hwiniszewski[@]chu-besancon.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: July 9, 2024
• Est. primary completion date: February 9, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiogenic Shock
• Extracorporeal Membrane Oxygenation
• Shock
• Shock, Cardiogenic

Intervention

Drug:
• Oxygen gas
Targeted PO2 postoxygenator is obtained by modulating ECMO Membrane oxygen fraction.

Locations

Country	Name	City	State
France	CHU de Besançon	Besancon

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Besancon

Country where clinical trial is conducted

France, 

References & Publications (4)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

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