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Liberal Oxygenation Versus Conservative Oxygenation in ARDS (LOCO2)

Primary Purpose

Acute Respiratory Distress Syndrome, Intensive Care

Status

Unknown status

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

Modulation of Inspired Fraction of Oxygen (FiO2)

About this trial

This is an interventional treatment trial for Acute Respiratory Distress Syndrome focused on measuring Oxygen

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

BARROT Loïc

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Liberal Oxygenation (LO) group

Conservative Oxygenation (CO) group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Death

Secondary Outcome Measures

Death

Days free of mechanical ventilation in ICU

Sequential Organ Failure Assessment (SOFA) Score

Sepsis-related Organ Failure Score

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

Ventilator associated pneumonia

Septicemia

Antibiotic consumption

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

Cardiovascular complications

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

Neurological evolution

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

Respiratory autonomy

Need for oxygen or mechanical ventilation support

Full Information

NCT ID

NCT02713451

First Posted

February 25, 2016

Last Updated

July 11, 2019

Sponsor

Centre Hospitalier Universitaire de Besancon

1. Study Identification

Unique Protocol Identification Number

NCT02713451

Brief Title

Liberal Oxygenation Versus Conservative Oxygenation in ARDS

Acronym

LOCO2

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2018

Overall Recruitment Status

Unknown status

Study Start Date

June 2016 (Actual)

Primary Completion Date

May 31, 2019 (Actual)

Study Completion Date

September 28, 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Centre Hospitalier Universitaire de Besancon

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Respiratory Distress Syndrome, Intensive Care

Keywords

Oxygen

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

206 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Liberal Oxygenation (LO) group

Arm Type

Active Comparator

Arm Description

Arm Title

Conservative Oxygenation (CO) group

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Modulation of Inspired Fraction of Oxygen (FiO2)

Intervention Description

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.

Primary Outcome Measure Information:

Title

Death

Time Frame

Day 28

Secondary Outcome Measure Information:

Title

Death

Time Frame

Day 90

Title

Days free of mechanical ventilation in ICU

Time Frame

Day 28

Title

Sequential Organ Failure Assessment (SOFA) Score

Description

Sepsis-related Organ Failure Score

Time Frame

Day 0, 3 and 7

Title

Score of morbidity

Description

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

Time Frame

Day 28

Title

Ventilator associated pneumonia

Time Frame

Day 28

Title

Septicemia

Time Frame

Day 28

Title

Antibiotic consumption

Description

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

Time Frame

Day 28

Title

Cardiovascular complications

Description

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

Time Frame

Day 28 and day 90

Title

Neurological evolution

Description

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

Time Frame

Day 28

Title

Respiratory autonomy

Description

Need for oxygen or mechanical ventilation support

Time Frame

Day 28 and 90

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Loïc Barrot, MD

Organizational Affiliation

BESANCON

Official's Role

Principal Investigator

Facility Information:

Facility Name

BARROT Loïc

City

Besancon

Country

France

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

26334785

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.

Results Reference

result

PubMed Identifier

32160661

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.

Results Reference

derived

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Liberal Oxygenation Versus Conservative Oxygenation in ARDS

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