Physiologic Effects of Continuous Positive Airway Pressure and High Flow Nasal Oxygenation in Patients with Acute Respiratory Distress Syndrome.

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.

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Respiratory Distress Syndrome (ARDS); Acute Respiratory Failure with Hypoxia
• Intervention / Treatment: Device: CPAP; Device: HFNO 50 L/min

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 Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ricard Mellado Artigas, PhD; Phone Number: +34 646217716; Email: rmellado@clinic.cat
• Study Contact Backup: Name: Jordi Vallverdú Martínez, MD; Phone Number: +34 622929752; Email: vallverdu@clinic.cat

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Recruiting
    • Hospital Clínic de Barcelona
    • Contact: Ricard Mellado Artigas, PhD; Phone Number: +34 646217716; Email: rmellado@clinic.cat
    • Contact: Jordi Vallverdú Martínez, MD; Phone Number: +34 622929752; Email: vallverdu@clinic.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CPAP; CPAP 12 cmH2O	Device: CPAP; 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.
Active Comparator: HFNO; HFNO 50 L/min.	Device: HFNO 50 L/min; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	From enrollment to the end of treatment at 48 hours.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Angiotensin-II	Endothelial pulmonary injury plasma biomarker.	From enrollment to the end of treatment at 48 hours.
Interleukin 6	Systemic inflammation biomarker.	From enrollment to the end of treatment at 48 hours.
Interleukin 10	Systemic inflammation biomarker	From enrollment to the end of treatment at 48 hours.
Orotraqueal intubation	Tracheal intubation rate	From enrollment to the end of treatment at 48 hours and at 90 days
Mortality	Mortality rate	From enrollment to 90 days

Collaborators and Investigators

• Sponsor: Ricard Mellado Artigas
• Collaborators: Hospital Clinic of Barcelona; Spanish Society of Pneumology and Thoracic Surgery
• Investigators: Study Director: Carlos M Ferrando Ortolá, PhD, Hospital Clinic of Barcelona

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2025
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): July 31, 2027

Study Registration Dates

• First Submitted: November 15, 2024
• First Submitted That Met QC Criteria: November 15, 2024
• First Posted (Actual): November 19, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 13, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Continuous positive airway pressure (CPAP); Transpulmonary pressure; Acute respiratory distress syndrome (ARDS); High flow nasal oxygenation; Patient self-inflicted lung injury (P-SILI); Soluble receptor of advanced glycation end-products (sRAGE)
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease; Lung Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Signs and Symptoms, Respiratory; Lung Injury; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Respiratory Insufficiency; Hypoxia; Acute Lung Injury
• Other Study ID Numbers: HCB/2023/1105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No