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Liberal Oxygenation Versus Conservative Oxygenation in ARDS

Phase 3
Conditions
Acute Respiratory Distress Syndrome
Intensive Care
Interventions
Drug: Modulation of Inspired Fraction of Oxygen (FiO2)
Registration Number
NCT02713451
Lead Sponsor
Centre Hospitalier Universitaire de Besancon
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.

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
206
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Liberal Oxygenation (LO) groupModulation of Inspired Fraction of Oxygen (FiO2)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.
Conservative Oxygenation (CO) groupModulation of Inspired Fraction of Oxygen (FiO2)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.
Primary Outcome Measures
NameTimeMethod
DeathDay 28
Secondary Outcome Measures
NameTimeMethod
Respiratory autonomyDay 28 and 90

Need for oxygen or mechanical ventilation support

Sequential Organ Failure Assessment (SOFA) ScoreDay 0, 3 and 7

Sepsis-related Organ Failure Score

Days free of mechanical ventilation in ICUDay 28
Score of morbidityDay 28

This score is based on three points: need for mechanical ventilation, need for Morbidity are renal replacement therapy, need of catecholamine or need for ventilation

SepticemiaDay 28
Antibiotic consumptionDay 28

Number of days exposed to antibiotics divided by the number of days spent in ICU

Cardiovascular complicationsDay 28 and day 90

New onset of rhythm disorders, cardiac ischemia and dose of catecholamin at 28 and 90 days

Ventilator associated pneumoniaDay 28
DeathDay 90
Neurological evolutionDay 28

Neurological evolution measured with daily Richmond Agitation Sedation Scale score, seizures, new stroke, daily sedation doses, neuroleptic administration

Trial Locations

Locations (1)

BARROT Loïc

🇫🇷

Besancon, France

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