Acute Respiratory Distress SyndromePhase 3LTO-BLOXYNCT03621293
Long Term Outcome on Brain and Lung of Different Oxygen Strategies in ARDS Patients
A Phase 3 study testing Modulation of Inspired Fraction of Oxygen (FiO2) in people with Acute Respiratory Distress Syndrome, run by Centre Hospitalier Universitaire de Besancon at 1 site in France.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome
- What is being tested?
- Modulation of Inspired Fraction of Oxygen (FiO2)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 259 participants
- Where
- 1 siteFrance
- Study dates
- 20 Sep 2017to 20 Sep 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ARDS defined as a PF ratio <300
- Patients under ventilation for <12 hours
- Stabilization period of 3 hours with standardization of ventilation parameters
- Patient aged between 20 and 89 years
Who cannot join
- 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
Show all 15Show fewer
- Indication for hyperbaric oxygen treatment
- Persistent pneumothorax
- Gaseous gangrene
- DNR or limited care order
- 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.
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
CHU de Besançon
Besançon, 25000
Bruno DEGANO, bruno.degano@univ-fcomte.fr
About this study
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
Read the 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.
- Conditions
- Acute Respiratory Distress Syndrome
- Being tested
- Modulation of Inspired Fraction of Oxygen (FiO2)
- Keywords
- Long term outcome, Brain, Lung, Oxygen strategies
- Medical subject headings
- Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
| Study group | Role | What they receive |
|---|---|---|
| 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.
Intervention: Drug: Modulation of Inspired Fraction of Oxygen (FiO2) Receives: 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.
Intervention: Drug: Modulation of Inspired Fraction of Oxygen (FiO2) Receives: Drug: Modulation of Inspired Fraction of Oxygen (FiO2) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 6 months
Secondary outcomes (11)
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.
Measured: 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
Measured: 6 months, 12 months
Respiratory function: plethysmography
Total lung capacity and functional residual capacity measured by plethysmography
Measured: 3 months, 6 months, 12 months
Respiratory function
FEV1 and FEV1/FVC ratio
Measured: 3 months, 6 months, 12 months
Respiratory function: blood gases
PaO2 and PaCO2 measured in room air at rest
Measured: 3 months, 6 months, 12 months
Respiratory function: inspiratory pressure
Sniff nasal inspiratory pressure (SNIP) and maximal inspiratory pressure (PImax) (diaphragm function).
Measured: 3 months, 6 months, 12 months
Exercise function: 6-min walk test
distance covered during a 6-minute walk test, in meters
Measured: 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
Measured: 6 months
Cognitive function: screening tests
Cognitive function will be investigated firstly through the use of rapid screening tests
Measured: 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
Measured: 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.
Measured: 3 months, 6 months, 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2018
- Study start20 Sep 2017
- Primary completion20 Mar 2021 (estimated)
- Study completion20 Sep 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de BesanconThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 259 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Besancon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03621293
- Sponsor's protocol ID
- N/2016/74
- Acronym
- LTO-BLOXY
- Status last verified
- Aug 2018
- First submitted
- 1 Aug 2018
- Last updated
- 8 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long Term Outcome on Brain and Lung of Different Oxygen Strategies in ARDS Patients
- ClinicalTrials.gov ID
- NCT03621293
- Acronym / sponsor ID
- LTO-BLOXY / N/2016/74
- Conditions
- Acute Respiratory Distress Syndrome
- Keywords
- Long term outcome, Brain, Lung, Oxygen strategies
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 259 participants (estimated)
- Lead sponsor
- Centre Hospitalier Universitaire de BesanconUniversity, hospital or other
- Study start
- 20 Sep 2017 (actual)
- Primary completion
- 20 Mar 2021 (estimated)
- Study completion
- 20 Sep 2021 (estimated)
- First posted
- 8 Aug 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Liberal Oxygenation (LO) group | Active comparator | Drug: Modulation 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. Intervention: Drug: Modulation of Inspired Fraction of Oxygen (FiO2) |
| Conservative Oxygenation (CO) group | Experimental | Drug: Modulation 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. Intervention: Drug: Modulation of Inspired Fraction of Oxygen (FiO2) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- ARDS defined as a PF ratio <300
- Patients under ventilation for <12 hours
- Stabilization period of 3 hours with standardization of ventilation parameters
- Patient aged between 20 and 89 years
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Conservative Oxygenation (CO) group, Liberal Oxygenation (LO) group |
Primary outcome
Diffusing Capacity of the Lungs for carbon monoxide (DLCO)
Time frame: 6 months
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
11 secondary outcomes
Evaluation of disability (Functional Independence Measure)
Time frame: inclusion, 6 months
A binary composite morbi-mortality variable
Time frame: 6 months, 12 months
Respiratory function: plethysmography
Time frame: 3 months, 6 months, 12 months
Respiratory function
Time frame: 3 months, 6 months, 12 months
Respiratory function: blood gases
Time frame: 3 months, 6 months, 12 months
Respiratory function: inspiratory pressure
Time frame: 3 months, 6 months, 12 months
Exercise function: 6-min walk test
Time frame: 3 months, 6 months, 12 months
Exercise function: cyclo ergometer
Time frame: 6 months
Cognitive function: screening tests
Time frame: inclusion, 3 months
Cognitive function
Time frame: 12 months
Quality of life: The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)
Time frame: 3 months, 6 months, 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Modulation of Inspired Fraction of Oxygen (FiO2) in people with Acute Respiratory Distress Syndrome, run by Centre Hospitalier Universitaire de Besancon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Bruno DEGANO, MD (3 81 21 87 45 ext. +33, bruno.degano@univ-fcomte.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diffusing Capacity of the Lungs for carbon monoxide (DLCO) (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2018.