Liberal Oxygenation Versus Conservative Oxygenation in ARDS

Acute Respiratory Distress Syndrome Clinical Trial

— LOCO2  

Official title:

Liberal Oxygenation Versus Conservative Oxygenation in Patients With Acute Respiratory Distress Syndrome : Impact on Mortality (LOCO2 Study)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02713451
• Other study ID #: R/2015/52
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 2016
• Est. completion date: September 28, 2019

Study information

• Verified date: November 2018
• Source: Centre Hospitalier Universitaire de Besancon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 206
• Est. completion date: September 28, 2019
• Est. primary completion date: May 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Intensive Care
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn
• Syndrome

Intervention

Drug:
• Modulation of Inspired Fraction of Oxygen (FiO2)
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.

Locations

Country	Name	City	State
France	BARROT Loïc	Besancon

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Besancon

Country where clinical trial is conducted

France, 

References & Publications (1)

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 Mult — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death		Day 28
Secondary	Death		Day 90
Secondary	Days free of mechanical ventilation in ICU		Day 28
Secondary	Sequential Organ Failure Assessment (SOFA) Score	Sepsis-related Organ Failure Score	Day 0, 3 and 7
Secondary	Score of morbidity	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	Day 28
Secondary	Ventilator associated pneumonia		Day 28
Secondary	Septicemia		Day 28
Secondary	Antibiotic consumption	Number of days exposed to antibiotics divided by the number of days spent in ICU	Day 28
Secondary	Cardiovascular complications	New onset of rhythm disorders, cardiac ischemia and dose of catecholamin at 28 and 90 days	Day 28 and day 90
Secondary	Neurological evolution	Neurological evolution measured with daily Richmond Agitation Sedation Scale score, seizures, new stroke, daily sedation doses, neuroleptic administration	Day 28
Secondary	Respiratory autonomy	Need for oxygen or mechanical ventilation support	Day 28 and 90