Acute Respiratory Distress Syndrome (ARDS)NCT06694311
Physiologic Effects of Continuous Positive Airway Pressure and High Flow Nasal Oxygenation in Patients with Acute Respiratory Distress Syndrome.
A study testing CPAP and HFNO 50 L/min in people with Acute Respiratory Distress Syndrome (ARDS) and Acute Respiratory Failure with Hypoxia, run by Ricard Mellado Artigas at 1 site in Spain.
Trial summary
The acute respiratory distress syndrome (ARDS) consists on a lack of breath due to fluid overload in the lungs that is not produced by a heart desease. Some people with this condition may need to be intubated and connected to invasive mechanical ventilation, but less severe cases may need supplementary oxygen that can… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Acute Respiratory Distress Syndrome (ARDS), Acute Respiratory Failure with Hypoxia
- What is being tested?
- CPAP and HFNO 50 L/min
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteSpain
- Study dates
- 7 Jan 2025to 31 Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PaO2/FiO2 ratio <300 mmHg with FiO2 >40% and PEEP ≥5 cmH2O (CPAP) or flow ≥30 L/min (HFNC).
- Bilateral pulmonary opacities observed in the chest X-ray, thoracic computerized tomography (CT) scan or lung ultrasonography (bilateral B lines)
- <7 days from the pulmonary insult to symptom onset and criteria 1 and 2
- Not meeting the aforementioned criteria for >24 hours prior to study inclusion.
Who cannot join
- Age <18 years or >80 years
- History of chronic respiratory failure or interstitial pulmonary disease
- Acute cardiogenic pulmonary edema after echocardiographic evaluation
- Having received either invasive mechanical ventilation or non-invasive mechanical ventilation (NIV)
- Atelectasis, pleural effusion, pulmonary masses or nodules as the primary finding in thoracic imaging.
- "Do not intubate, do not resuscitate" orders
- Presenting significant nasal obstruction.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Spain1 site, 1 recruiting
- Recruiting
Hospital Clínic de Barcelona
Barcelona, Barcelona, 08036
Ricard Mellado Artigas, PhD, +34 646217716, rmellado@clinic.cat
Jordi Vallverdú Martínez, MD, +34 622929752, vallverdu@clinic.cat
About this study
Official title: Physiologic Effects of Two Non-invasive Respiratory Support Therapies (continuous Positive Airway Pressure Vs High Flow Nasal Oxygenation) in Patients with Acute Respiratory Distress Syndrome: a Randomized Clinical Trial.
The acute respiratory distress syndrome (ARDS) consists on a lack of breath due to fluid overload in the lungs that is not produced by a heart desease. Some people with this condition may need to be intubated and connected to invasive mechanical ventilation, but less severe cases may need supplementary oxygen that can be delivered with non-invasive devices, such as CPAP (continuous positive airway pressure) or HFNO (high flow nasal oxygenation). CPAP consists on a facemask that provides oxygen-enriched air at a high pressure, whereas HFNO consists on nasal cannula that provides oxygen-enriched air at a high flow.
Patients with ARDS may present with high respiratory efforts that can eventually damage their own lungs and contribute to the development of a phenomenon known as patient self-inflicted lung injury (P-SILI). Previous research has identified that CPAP may be successful in attuenuating P-SILI compared to HFNO, but it is not known whether this attenuation actually results into a reduction in lung injury in real patients.
Read more
In this multicentre trial, 120 non-intubated patients with stablished ARDS will be randomly assigned to receive oxygen-enriched air through either CPAP or HFNO for 48 hours plus standard intensive care. The primary goal of this study is to determine the pulmonary effect of CPAP and HFNO through lung injury biomarkers that can be detected in blood, such as sRAGE (soluble Receptor of Advanced Glycation End-products), angiotensin-II, interleukin-6 and interleukin-10. It will also be studied whether CPAP reduces 48-hour traqueal intubation rate, 90-day traqueal intubation rate and 90-day mortality.
Identifying that CPAP attenuates lung injury in spontaneously breathing ARDS patients will help clinicians to better understand this condition and to better treat this patients, so they do not evenutally need traqueal intubation and connection to invasive mechanical ventilation.
Read the detailed description
The acute respiratory distress syndrome (ARDS) is defined as an acute hypoxemic respiratory failure with non-cardiogenic pulmonary opacities. This condition has been recently extended to non-intubated patients. Patients under non-invasive respiratory support might present with high transpulmonary pressures, pulmonary strain and pendelluft, which contribute to the development of patient self-inflicted lung injury (P-SILI). Previous studies have identified that continuous positive airway pressure (CPAP) is successful in attenuating P-SILI effectors compared to high flow nasal oxygenation (HFNO). However, it remains uncertain whether this attenuation actually results into a reduction in lung injury and improved clinical outcomes.
This is a multicentre, randomised, open-label, controlled trial. 120 non-intubated patients with established ARDS will be randomly assigned to receive non-invasive respiratory support with either CPAP 12 cmH2O or HFNO 50 L/min for 48 hours plus standard intensive care. The primary outcome is biological lung injury evaluated through the epithelial pulmonary dysfunction biomarker sRAGE (soluble Receptor of Advanced Glycation End-products). Secondary outcomes include plasmatic pulmonary dysfunction biomarkers (angiotensin-II, interleukin-6, interleukin-10), P-SILI effectors (pulmonary strain, pendelluft, transpulmonary pressure), 48-hour traqueal intubation rate, 90-day traqueal intubation rate and 90-day mortality. All analyses will be conducted according to the intention-to-treat principle.
This study will assess the potential role of CPAP in attenuating P-SILI effectors and inflicting less biological lung injury compared to HFNO. This physiologic effect may lead to lower rates of traqueal intubation and mortality. This project will provide new knowledge on the respiratory management of non-intubated ARDS patients, a subject where evidence is lacking.
- Being tested
- CPAP, HFNO 50 L/min
- Keywords
- Acute respiratory distress syndrome (ARDS), Continuous positive airway pressure (CPAP), High flow nasal oxygenation, Patient self-inflicted lung injury (P-SILI), Soluble receptor of advanced glycation end-products (sRAGE), Transpulmonary pressure
- 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.
CPAPDevice
12 cmH2O for 48 hours (at least 10 hours of therapy per day). Nasobucal interface will be the preferred route with complete facial mask being also an acceptable device. If needed, therapy breaks will be delivered with HFNO at 50 L/min.
Non-invasive ventilation will not be allowed.
After 48 hours of treatment, clinicians will be able to decide the respiratory support to be provided although CPAP will be recommended to be continued as long as PaO2/FiO2 is less than or equal to 300 and inspired oxygen fraction is 40% or more.
HFNO 50 L/minDevice
HFNO 50 L/min for 48 hours. Therapy breaks with oxygen facemask will be allowed as per clinician decision but the protocol will advise against this practice.
Non-invasive ventilation will not be allowed.
After 48 hours of treatment, clinicians will be able to decide the respiratory support to be provided although HFNO will be recommended to be continued as long as PaO2/FiO2 is less than or equal to 300 and inspired oxygen fraction is 40% or more.
| Study group | Role | What they receive |
|---|---|---|
| CPAP | Experimental | CPAP 12 cmH2O Receives: Device: CPAP |
| HFNO | Active comparator | HFNO 50 L/min. Receives: Device: HFNO 50 L/min |
What is being measured
The primary outcome is the main question the study is designed to answer.
sRAGE
The primary outcome of this project is sRAGE, a plasma biomarker indicative of pulmonary epithelial dysfunction. This comparator was selected due to its established association with ventilator-induced lung injury (VILI) and mortality in intubated ARDS patients. sRAGE has got an excellent capacity to detect driving pressure >14 cmH2O in ARDS patients undergoing invasive mechanical ventilation. This suggests that sRAGE may be an adequate biomarker for detecting pulmonary strain in non-intubated ARDS patients.
Measured: From enrollment to the end of treatment at 48 hours.
Secondary outcomes (5)
Angiotensin-II
Endothelial pulmonary injury plasma biomarker.
Measured: From enrollment to the end of treatment at 48 hours.
Interleukin 6
Systemic inflammation biomarker.
Measured: From enrollment to the end of treatment at 48 hours.
Interleukin 10
Systemic inflammation biomarker
Measured: From enrollment to the end of treatment at 48 hours.
Orotraqueal intubation
Tracheal intubation rate
Measured: From enrollment to the end of treatment at 48 hours and at 90 days
Mortality
Mortality rate
Measured: From enrollment to 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2024
- Study start7 Jan 2025
- Primary completion30 Apr 2026 (estimated)
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Respiratory Distress Syndrome (ARDS)Studies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a multicentric, randomized, open label, controlled, superiority clinical trial. Participants will undergo permuted block randomization with a ratio 1:1.
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ricard Mellado Artigas
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Clinic of Barcelona, Spanish Society of Pneumology and Thoracic Surgery
- Responsible party
- Sponsor-investigator, Ricard Mellado Artigas, Hospital Clinic of Barcelona
- Investigators
- Carlos M Ferrando Ortolá, PhD, Study director, Hospital Clinic of Barcelona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06694311
- Sponsor's protocol ID
- HCB/2023/1105
- Status last verified
- Jan 2025
- First submitted
- 15 Nov 2024
- Last updated
- 15 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Vallverdu J, Barbeta E, Mellado R, Torres A, Ferrando C. Physiologic effects of two non-invasive respiratory support therapies (continuous positive airway pressure versus high-flow nasal oxygenation) in patients with acute respiratory distress syndrome: study protocol for a randomized clinical trial. Trials. 2026 Jan 2;27(1):98. doi: 10.1186/s13063-025-09344-1.
PubMed 41484920
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Physiologic Effects of Two Non-invasive Respiratory Support Therapies (continuous Positive Airway Pressure Vs High Flow Nasal Oxygenation) in Patients with Acute Respiratory Distress Syndrome: a Randomized Clinical Trial.
- ClinicalTrials.gov ID
- NCT06694311
- Acronym / sponsor ID
- HCB/2023/1105
- Keywords
- Acute respiratory distress syndrome (ARDS), Continuous positive airway pressure (CPAP), High flow nasal oxygenation, Patient self-inflicted lung injury (P-SILI), Soluble receptor of advanced glycation end-products (sRAGE), Transpulmonary pressure
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Ricard Mellado ArtigasUniversity, hospital or other
- Collaborators
- Hospital Clinic of Barcelona, Spanish Society of Pneumology and Thoracic Surgery
- Study start
- 7 Jan 2025 (actual)
- Primary completion
- 30 Apr 2026 (estimated)
- Study completion
- 31 Jul 2027 (estimated)
- First posted
- 19 Nov 2024 (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.
The acute respiratory distress syndrome (ARDS) consists on a lack of breath due to fluid overload in the lungs that is not produced by a heart desease. Some people with this condition may need to be intubated and connected to invasive mechanical ventilation, but less severe cases may need supplementary oxygen that can be delivered with non-invasive devices, such as CPAP (continuous positive airway pressure) or HFNO (high flow nasal oxygenation). CPAP consists on a facemask that provides oxygen-enriched air at a high pressure, whereas HFNO consists on nasal cannula that provides oxygen-enriched air at a high flow.
Patients with ARDS may present with high respiratory efforts that can eventually damage their own lungs and contribute to the development of a phenomenon known as patient self-inflicted lung injury (P-SILI). Previous research has identified that CPAP may be successful in attuenuating P-SILI compared to HFNO, but it is not known whether this attenuation actually results into a reduction in lung injury in real patients.
In this multicentre trial, 120 non-intubated patients with stablished ARDS will be randomly assigned to receive oxygen-enriched air through either CPAP or HFNO for 48 hours plus standard intensive care. The primary goal of this study is to determine the pulmonary effect of CPAP and HFNO through lung injury biomarkers that can be detected in blood, such as sRAGE (soluble Receptor of Advanced Glycation End-products), angiotensin-II, interleukin-6 and interleukin-10. It will also be studied whether CPAP reduces 48-hour traqueal intubation rate, 90-day traqueal intubation rate and 90-day mortality.
Identifying that CPAP attenuates lung injury in spontaneously breathing ARDS patients will help clinicians to better understand this condition and to better treat this patients, so they do not evenutally need traqueal intubation and connection to invasive mechanical ventilation.
Detailed description
The acute respiratory distress syndrome (ARDS) is defined as an acute hypoxemic respiratory failure with non-cardiogenic pulmonary opacities. This condition has been recently extended to non-intubated patients. Patients under non-invasive respiratory support might present with high transpulmonary pressures, pulmonary strain and pendelluft, which contribute to the development of patient self-inflicted lung injury (P-SILI). Previous studies have identified that continuous positive airway pressure (CPAP) is successful in attenuating P-SILI effectors compared to high flow nasal oxygenation (HFNO). However, it remains uncertain whether this attenuation actually results into a reduction in lung injury and improved clinical outcomes.
This is a multicentre, randomised, open-label, controlled trial. 120 non-intubated patients with established ARDS will be randomly assigned to receive non-invasive respiratory support with either CPAP 12 cmH2O or HFNO 50 L/min for 48 hours plus standard intensive care. The primary outcome is biological lung injury evaluated through the epithelial pulmonary dysfunction biomarker sRAGE (soluble Receptor of Advanced Glycation End-products). Secondary outcomes include plasmatic pulmonary dysfunction biomarkers (angiotensin-II, interleukin-6, interleukin-10), P-SILI effectors (pulmonary strain, pendelluft, transpulmonary pressure), 48-hour traqueal intubation rate, 90-day traqueal intubation rate and 90-day mortality. All analyses will be conducted according to the intention-to-treat principle.
This study will assess the potential role of CPAP in attenuating P-SILI effectors and inflicting less biological lung injury compared to HFNO. This physiologic effect may lead to lower rates of traqueal intubation and mortality. This project will provide new knowledge on the respiratory management of non-intubated ARDS patients, a subject where evidence is lacking.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- This is a multicentric, randomized, open label, controlled, superiority clinical trial. Participants will undergo permuted block randomization with a ratio 1:1.
| Arm | Type | Receives |
|---|---|---|
| CPAP | Experimental | Device: CPAPCPAP 12 cmH2O |
| HFNO | Active comparator | Device: HFNO 50 L/minHFNO 50 L/min. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- PaO2/FiO2 ratio <300 mmHg with FiO2 >40% and PEEP ≥5 cmH2O (CPAP) or flow ≥30 L/min (HFNC).
- Bilateral pulmonary opacities observed in the chest X-ray, thoracic computerized tomography (CT) scan or lung ultrasonography (bilateral B lines)
- <7 days from the pulmonary insult to symptom onset and criteria 1 and 2
- Not meeting the aforementioned criteria for >24 hours prior to study inclusion.
Key exclusion criteria (7 listed)
- Age <18 years or >80 years
- History of chronic respiratory failure or interstitial pulmonary disease
- Acute cardiogenic pulmonary edema after echocardiographic evaluation
- Having received either invasive mechanical ventilation or non-invasive mechanical ventilation (NIV)
- Atelectasis, pleural effusion, pulmonary masses or nodules as the primary finding in thoracic imaging.
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 |
|---|---|---|
| CPAP12 cmH2O for 48 hours (at least 10 hours of therapy per day). Nasobucal interface will be the preferred route with complete facial mask being also an acceptable device. If needed, therapy breaks will be delivered with HFNO at 50 L/min. Non-invasive ventilation will not be allowed. After 48 hours of treatment, clinicians will be able to decide the respiratory support to be provided although CPAP will be recommended to be continued as long as PaO2/FiO2 is less than or equal to 300 and inspired oxygen fraction is 40% or more. | Device | CPAP |
| HFNO 50 L/minHFNO 50 L/min for 48 hours. Therapy breaks with oxygen facemask will be allowed as per clinician decision but the protocol will advise against this practice. Non-invasive ventilation will not be allowed. After 48 hours of treatment, clinicians will be able to decide the respiratory support to be provided although HFNO will be recommended to be continued as long as PaO2/FiO2 is less than or equal to 300 and inspired oxygen fraction is 40% or more. | Device | HFNO |
Primary outcome
sRAGE
Time frame: From enrollment to the end of treatment at 48 hours.
The primary outcome of this project is sRAGE, a plasma biomarker indicative of pulmonary epithelial dysfunction. This comparator was selected due to its established association with ventilator-induced lung injury (VILI) and mortality in intubated ARDS patients. sRAGE has got an excellent capacity to detect driving pressure >14 cmH2O in ARDS patients undergoing invasive mechanical ventilation. This suggests that sRAGE may be an adequate biomarker for detecting pulmonary strain in non-intubated ARDS patients.
5 secondary outcomes
Angiotensin-II
Time frame: From enrollment to the end of treatment at 48 hours.
Interleukin 6
Time frame: From enrollment to the end of treatment at 48 hours.
Interleukin 10
Time frame: From enrollment to the end of treatment at 48 hours.
Orotraqueal intubation
Time frame: From enrollment to the end of treatment at 48 hours and at 90 days
Mortality
Time frame: From enrollment to 90 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2025.
- Derived from this study: PubMed 41484920Vallverdu J, Barbeta E, Mellado R, Torres A, Ferrando C. Physiologic effects of two non-invasive respiratory support therapies (continuous positive airway pressure versus high-flow nasal oxygenation) in patients with acute respiratory distress syndrome: study protocol for a randomized clinical trial. Trials. 2026 Jan 2;27(1):98. doi: 10.1186/s13063-025-09344-1.
- Individual participant dataSharing planned: Yes
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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.
Carlos M Ferrando Ortolá, PhD study director
Hospital Clinic of Barcelona
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CPAP and HFNO 50 L/min in people with Acute Respiratory Distress Syndrome (ARDS) and Acute Respiratory Failure with Hypoxia, run by Ricard Mellado Artigas at 1 site in Spain.
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 7 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: looking for participants now, as of the sponsor's last update on 15 Jan 2025. 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 Spain. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ricard Mellado Artigas, PhD (+34 646217716, rmellado@clinic.cat), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
sRAGE (time frame: From enrollment to the end of treatment at 48 hours.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06694311, which also lists 1 linked publication.
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 15 Jan 2025.