Long Term Outcome on Brain and Lung of Different Oxygen Strategies in ARDS Patients (LTO-BLOXY)

Acute respiratory distress syndrome (ARDS) is a serious disease with high mortality. In patients who survive ARDS, respiratory, neurological and motor sequelae are frequent, negatively impacting on the patient's quality of life, and engendering substantial healthcare costs (rehabilitation, long-term care, delayed return to work). There may also be repercussions on the patient's family and entourage. The severity of ARDS and the burden it represents have underpinned intensive research to identify treatment strategies that could improve mortality. However, it is important to ensure that any improvement in mortality does not come at the price of an excess of sequelae and disability in survivors.

The oxygenation strategy used to treat ARDS may have an impact on mortality in these patients. The CLOSE study, in which our group participated, recently demonstrated the feasibility of two oxygenation strategies in intensive care unit (ICU) patients with ARDS. We have also initiated the LOCO-2 study (NCT02713451), whose aim is to show a reduction in mortality in ARDS using a "conservative" oxygenation strategy (PaO2 maintained between 55 and 70 mmHg) as compared to a classical "liberal" oxygenation strategy (PaO2 between 90 and 105 mmHg).

The LTO-BLOXY study is a substudy of the on-going LOCO-2 study

Study Overview

• Status: Unknown
• Conditions: Acute Respiratory Distress Syndrome
• Intervention / Treatment: Drug: Modulation of Inspired Fraction of Oxygen (FiO2)

Detailed Description

The LTO-BLOXY study will compare respiratory, cognitive and exercise function outcomes in patients who underwent one of the two oxygenation strategies in the context of the on-going LOCO-2 study:

• Experimental group: oxygenation will be maintained at a level between 55 and 70 mmHg of PaO2 as measured by blood gas test ("conservative" oxygenation). Between blood gas measures, oxygenation will be optimized to achieve an SpO2 between 88% and 92%.
• Control group: oxygenation will be maintained at a level between 90 and 105 mmHg of PaO2 as measured by blood gas test ("liberal" oxygenation). Between blood gas measures, oxygenation will be optimized to achieve an SpO2 >96%.

The primary objective is to demonstrate a lower level of impairment of respiratory function at 6 months in survivors of acute respiratory distress syndrome (ARDS) after a "conservative" oxygenation strategy, as compared to a "liberal" oxygenation strategy.

Secondary objectives are numerous and will explore different areas such as evalution of disability, respiratory function, exercise function, cognitive function and quality of life.

Participation in the LTO-BLOXY study will be proposed to all patients included in LOCO-2 at discharge from the ICU. A total of 259 patients from the overall total of 850 expected inclusions in LOCO-2, will participate in the LTO-BLOXY study. These patients will be followed up to 1 year after their initial inclusion in LOCO-2, with a view to evaluate respiratory function, exercise function and cognitive function, as well as QoL.

The calendar of their study participation is as follows:

• Inclusion in LOCO-2 study and randomization LOCO-2
• Inclusion in LTO-BLOXY study at discharge from the ICU
• 3 month visit ± 2 weeks (3 months after inclusion in LOCO-2 study)
• 6 month visit ± 2 weeks (6 months after inclusion in LOCO-2 study)
• 12 month visit ± 2 weeks (12 months after inclusion in LOCO-2 study)

At each follow-up visit, the patient will attend a consultation in the Department of Physiology - Functional Explorations, where the study questionnaires will be given to the patient for completion. The neuropsychologist will perform the cognitive tests, the respiratory function and exercise tests will also be performed at the same visit.

• Study Type: Interventional
• Enrollment (Anticipated): 259
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Bruno DEGANO, MD; Phone Number: +33 3 81 21 87 45; Email: bruno.degano@univ-fcomte.fr
• Study Contact Backup: Name: Sophie DEPIERRE; Phone Number: +33 3 81 21 87 45; Email: sdepierre@chu-besancon.fr

Study Locations

• France
  • Besancon, France, 25000
    • Recruiting
    • CHU de Besancon
    • Contact: Bruno DEGANO; Email: bruno.degano@univ-fcomte.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ARDS defined as a PF ratio <300
• Patients under ventilation for <12 hours
• Stabilization period of 3 hours with standardization of ventilation parameters

Inclusion criterion specific for neurological evaluation:

- Patient aged between 20 and 89 years

Exclusion Criteria:

• Chronic respiratory failure or on home ventilation (excluding obstructive sleep apnoea)
• Cardiac arrest
• Moribund patients (death likely within 48 hours as assessed by the ICU physician)
• Gaseous embolism
• CO poisoning
• Pregnant women
• Indication for hyperbaric oxygen treatment
• Persistent pneumothorax
• Gaseous gangrene
• DNR or limited care order

Exclusion criteria specific for neurological evaluation:

• History of neurological disorders: cranial trauma, stroke, cerebral tumor, epilepsy, neuro-degenerative disease.
• Psychiatric disorders: bipolar disorder, psychosis, addiction, schizophrenia.
• Lack of autonomy due to previously documented cognitive and/or psychomotor impairment.
• Hearing and/or sight impairment that prevent the patient from performing the study tests

Patients presenting exclusion criteria for the neurological evaluation can nonetheless be included in the study for the evaluation of respiratory function.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Liberal Oxygenation (LO) group; 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. Intervention: Drug: Modulation of Inspired Fraction of Oxygen (FiO2)	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.
Experimental: Conservative Oxygenation (CO) group; 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. Intervention: Drug: Modulation of Inspired Fraction of Oxygen (FiO2)	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diffusing Capacity of the Lungs for carbon monoxide (DLCO)	The primary endpoint is the diffusing capacity of the lungs for carbon monoxide (DLCO), a measure that reflects disorders in pulmonary gas volume, the alveolar-capillary membrane, and the volume of blood in the lung capillaries	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of disability (Functional Independence Measure)	FIM scale to assess the patient's performance in the activities of daily living, including cognitive and relational aspects.	inclusion, 6 months
A binary composite morbi-mortality variable	A binary composite morbi-mortality variable defined as follow: Failure: death or poor FIM; Success: alive and good recuperation	6 months, 12 months
Respiratory function: plethysmography	Total lung capacity and functional residual capacity measured by plethysmography	3 months, 6 months, 12 months
Respiratory function	FEV1 and FEV1/FVC ratio	3 months, 6 months, 12 months
Respiratory function: blood gases	PaO2 and PaCO2 measured in room air at rest	3 months, 6 months, 12 months
Respiratory function: inspiratory pressure	Sniff nasal inspiratory pressure (SNIP) and maximal inspiratory pressure (PImax) (diaphragm function).	3 months, 6 months, 12 months
Exercise function: 6-min walk test	distance covered during a 6-minute walk test, in meters	3 months, 6 months, 12 months
Exercise function: cyclo ergometer	Physiological parameters measured at peak effort limited by symptoms on a bicycle ergometer exercise test	6 months
Cognitive function: screening tests	Cognitive function will be investigated firstly through the use of rapid screening tests	inclusion, 3 months
Cognitive function	Cognitive function will be investigated secondly through an evaluation performed by a neuropsychologist through the use of the RAPID battery	12 months
Quality of life: The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)	The SF36, in its validated French language version, is an established instrument used to evaluate quality of life (QoL).The questionnaire yields an overall score between 0 and 100, with a higher score indicating better QoL.	3 months, 6 months, 12 months

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Besancon

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2017
• Primary Completion (Anticipated): March 20, 2021
• Study Completion (Anticipated): September 20, 2021

Study Registration Dates

• First Submitted: August 1, 2018
• First Submitted That Met QC Criteria: August 7, 2018
• First Posted (Actual): August 8, 2018

Study Record Updates

• Last Update Posted (Actual): August 8, 2018
• Last Update Submitted That Met QC Criteria: August 7, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: Lung; Brain; Long term outcome; Oxygen strategies
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Lung Diseases; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: N/2016/74

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No