Clinical trial NCT04990349: Normoxemic Versus Hyperoxemic Extracorporeal Oxygenation in Patients Supported by Veino-arterial ECMO for Cardiogenic Shock
Official title: Normoxemic Versus Hyperoxemic Extracorporeal Oxygenation : Impact on Organ Dysfunction in Patients Supported by Veino-arterial ECMO for Cardiogenic Shock
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiogenic Shock
Extracorporeal Membrane Oxygenation
Keywords: Cardiogenic shock
Extracorporeal Membrane Oxygenation
Hyperoxia
Lead sponsor: Centre Hospitalier Universitaire de Besancon
Sponsor class: OTHER
First posted: 2021-08-04
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial with two arms
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Enterocyte damage
timeFrame: At day 2
Secondary outcomes:
measure: Feasibility of the oxygenation protocol
timeFrame: From day 0 to day 6
measure: Security of the oxygenation protocol
timeFrame: From day 0 to day 6
measure: Organ failure
timeFrame: From day 0 to day 30
measure: Organ failure
timeFrame: At day 0, day 2 and day 6
measure: Organ failure
timeFrame: At day 0, day 2 and day 6
measure: Enterocyte damage
timeFrame: At day 0, and day 1
measure: Enterocyte function
timeFrame: At day 0 and day 2
measure: Liver failure
timeFrame: At day 0, day 2 and day 6
measure: Liver failure
timeFrame: At day 0, day 2 and day 6
measure: Renal failure
timeFrame: At day 0, day 2 and day 6
measure: Renal failure
timeFrame: From 0 to day 6
measure: Systemic inflammation
timeFrame: At day 0, day 2 and day 6
measure: Anti-oxydant stock
timeFrame: At day 0, day 2 and day 6
Other outcomes:
Locations:
city: Besancon
country: France
facility: CHU de Besançon
Study officials:
References:
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.
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.
citation: 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.
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.