Clinical trial NCT02713451: Liberal Oxygenation Versus Conservative Oxygenation in ARDS
Official title: Liberal Oxygenation Versus Conservative Oxygenation in Patients With Acute Respiratory Distress Syndrome : Impact on Mortality (LOCO2 Study)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Acute Respiratory Distress Syndrome
Intensive Care
Keywords: Oxygen
Lead sponsor: Centre Hospitalier Universitaire de Besancon
Sponsor class: OTHER
First posted: 2016-03-18
Enrollment: 206
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: No clear recommendation exists for the level of oxygenation of intensive care patients. In Acute Respiratory Distress Syndrome (ARDS), pulsed oxymetry (SpO2) have to be kept between 88 and 95 percent and oxygen alveolar pressure between 55 and 80 mmHg (PaO2). These recommendations are common but do not lie on high scientific knowledge and level of proof. In the major studies of these fifteen last years that changed ARDS management, PaO2 was kept around 85 and 90 mmHg despite current recommendations of 55 to 80 mmHg of PaO2.

Many recent review and cohort studies pointed the risk of excessive oxygenation especially following cardiac arrest, stroke or traumatic brain injury. However, these data come in majority from cohort or database study without strong definition of hyperoxia. Data coming from prospective studies are scarce and tend to show better outcome of patients with lower objectives of oxygenation in ICU.

High oxygen (O2) level may be deleterious especially on inflammatory lungs. It could enhance injuries due to mechanical ventilation. O2 could be responsable of " hyperoxia induced lung injury ".

The investigators showed in a precedent study that comparing a restrictive oxygenation versus a liberal oxygenation was feasable and do not expose patients to major adverse events. More, mortality at 60 days has tendency to be lower. The investigators therefore ask if a lower objectives of PaO2 in comparison with the level usually seen in last studies on ARDS could improve ARDS patients outcome.

The aim of this study is to show that a restrictive oxygenation in comparison with a liberal oxygenation strategy in patients with ARDS would lower mortality at 28 days.

Detailed description: It is a prospective, comparative, randomized, multicentric, french, open study. Patients with ARDS will be enrolled and will be allocated to Liberal Oxygenation arm (LO) or to Conservative Oxygenation arm (CO) during the invasive mechanical ventilation procedure in ICU.

In LO arm, objective of PaO2 is 90 to 105 mmHg. In CO arm, objective of PaO2 is 55 to 70 mmHg.

Eligibility criteria: Inclusion Criteria:

* Major patients with mechanical ventilation
* ARDS according to Berlin definition:Hypoxemia defined with PaO2 FiO2 ratio less or equal to 300 mmHg with Positive End Expiratory Pressure higher or equal to 5 cmH20, Less than seven days between a known clinical insult or new or worsening of respiratory symptoms, Bilateral opacities on chest Imaging not fully explained by effusions, lobar or lung collapse, or nodules, Respiratory failure not fully explained by cardiac failure or fluid overload
* Less than twelve hours following initiation of mechanical ventilation.

Exclusion Criteria:

* Pregnancy
* Patient less than 18 years old
* Sickle cell disease
* Patient deprived of freedom, Under a legal protective measure
* Cardiac arrest as the reason for ICU hospitalisation
* Traumatic brain injury as the reason for ICU hospitalisation
* Hemoptysis with embolization or surgery
* Extracorporeal life support or Extracorporeal Membrane Oxygenation before randomization
* Chronic Obstructive Pulmonary Disease with oxygen or non invasive ventilation at home (obstructive sleep apnoea syndrome is not an exclusion criteria)
* Patient with very high risk of death with IGS II (Simplified Severity Index II) than 90
* Indication of hyperbaric oxygenation : carbon monoxide intoxication, gas embolism, necrotizing fasciitis
* Cyanide intoxication, methemoglobinemia
* Untreated pneumothorax
* Lymphangitis carcinomatosa
* Eosinophilic pneumonia
* Intensive care management for organ donation
* Participation in another interventional study with mortality as a major outcome to avoid confounding factor
* Patient not affiliated to social security

Primary outcomes:
measure: Death
timeFrame: Day 28
Secondary outcomes:
measure: Death
timeFrame: Day 90
measure: Days free of mechanical ventilation in ICU
timeFrame: Day 28
measure: Sequential Organ Failure Assessment (SOFA) Score
timeFrame: Day 0, 3 and 7
measure: Score of morbidity
timeFrame: Day 28
measure: Ventilator associated pneumonia
timeFrame: Day 28
measure: Septicemia
timeFrame: Day 28
measure: Antibiotic consumption
timeFrame: Day 28
measure: Cardiovascular complications
timeFrame: Day 28 and day 90
measure: Neurological evolution
timeFrame: Day 28
measure: Respiratory autonomy
timeFrame: Day 28 and 90
Other outcomes:
Locations:
city: Besancon
country: France
facility: BARROT Loïc
Study officials:
affiliation: BESANCON
name: Loïc Barrot, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Panwar R, Hardie M, Bellomo R, Barrot L, Eastwood GM, Young PJ, Capellier G, Harrigan PW, Bailey M; CLOSE Study Investigators; ANZICS Clinical Trials Group. Conservative versus Liberal Oxygenation Targets for Mechanically Ventilated Patients. A Pilot Multicenter Randomized Controlled Trial. Am J Respir Crit Care Med. 2016 Jan 1;193(1):43-51. doi: 10.1164/rccm.201505-1019OC.
citation: Barrot L, Asfar P, Mauny F, Winiszewski H, Montini F, Badie J, Quenot JP, Pili-Floury S, Bouhemad B, Louis G, Souweine B, Collange O, Pottecher J, Levy B, Puyraveau M, Vettoretti L, Constantin JM, Capellier G; LOCO2 Investigators and REVA Research Network. Liberal or Conservative Oxygen Therapy for Acute Respiratory Distress Syndrome. N Engl J Med. 2020 Mar 12;382(11):999-1008. doi: 10.1056/NEJMoa1916431.