Liberal Oxygenation Versus Conservative Oxygenation in ARDS

NCT02713451 | Unknown Phase 3 DMC

• 1 other identifier: R/2015/52
• Study Type: interventional
• Target: 206
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Respiratory Distress Syndrome; Intensive Care

Keywords

Oxygen

Outcome Measures

Primary Outcomes (1)

• Death

  Day 28

Secondary Outcomes (10)

• Death

  Day 90

• Days free of mechanical ventilation in ICU

  Day 28

• Sequential Organ Failure Assessment (SOFA) Score

  Day 0, 3 and 7

• Score of morbidity

  Day 28

• Ventilator associated pneumonia

  Day 28

Study Arms (2)

Liberal Oxygenation (LO) group

ACTIVE COMPARATOR

A modulation of inspired fraction of oxygen will be performed with an objective of PaO2 between 90 to 105 mmHg that will be checked on arterial blood gases (ABG). Between these measurements, SpO2 will be kept more or equal to 96 percent. Alarms will be set at 95 percent for SpO2.

Drug: Modulation of Inspired Fraction of Oxygen (FiO2)

Conservative Oxygenation (CO) group

EXPERIMENTAL

A modulation of inspired fraction of oxygen will be performed with an objective of PaO2 between 55 to 70 mmHg that will be checked on arterial blood gases. Between these measurements, SpO2 will be kept between 88 and 92 percent. Alarms will be set between 87 and 93 percent for SpO2.

Drug: Modulation of Inspired Fraction of Oxygen (FiO2)

Interventions

Modulation of Inspired Fraction of Oxygen (FiO2) DRUG

In the two groups, if patient is not in the range of arterial oxygen pressure (PaO2), Inspired Fraction of Oxygen (FiO2) will be modified from 5 percent if difference between target is less than 5 mmHg and from 10 percent if difference from target is higher. A new arterial blood gases (ABG) will be performed 30 minutes later to check for the oxygen target range. When ABG are performed, pulsed oxymetry is compared with arterial saturation (SaO2) to adapt survey. Between each ABG, FiO2 is modified from 5 percent to 5 percent each five minutes until reaching good pulsed oxygen saturation (SpO2) target (that can be modified in function of the comparison of arterial oxygen saturation (SaO2 and SpO2 with ABG). This management of FiO2 will be done until extubation of the patient.

Conservative Oxygenation (CO) group; Liberal Oxygenation (LO) group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Besancon: lead

Study Sites (1)

BARROT Loïc

Besançon, France

Location

Related Publications (2)

• 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.

  PMID: 26334785 RESULT

• 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.

  PMID: 32160661 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Study Officials

• Loïc Barrot, MD

  BESANCON

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2016
• First Posted: March 18, 2016
• Study Start: June 1, 2016
• Primary Completion: May 31, 2019
• Study Completion: September 28, 2019
• Last Updated: July 12, 2019

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)