An observational study in Acute Hypoxemic Respiratory Failure and Acute Respiratory Distress Syndrome, sponsored by Evangelismos Hospital. Recruiting at 1 site in Greece. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-15.
Sponsored by Evangelismos Hospital · Observational
We attempt to perform dynamic endotyping of critically ill patients presenting in the emergency department with de novo acute hypoxemic respiratory failure (AHRF). We also attempt to identify what clinical, radiological, physiological and biological variables collected early in the course of AHRF correlate with subsequent mortality and/or persistent severe hypoxemia.
Rationale:
Even before the pandemic of the new coronavirus disease (COVID-19), acute respiratory distress syndrome (ARDS), the most severe form of acute hypoxemic respiratory failure (AHRF), constituted a public health challenge. Despite the intense research on identifying targeted pharmacological therapies for ARDS, there is no available treatment for the syndrome.
The failure of clinical trials exploring pharmacological therapies for ARDS has been attributed to incomplete understanding of the pathogenesis and heterogeneity of the syndrome. As examples of the heterogeneity of ARDS, our recent work has identified differential outcomes of patients with ARDS depending on whether hypoxemia is rapidly improving or persistent severe or associated with non-identifiable risk factors or associated with neutropenia. It is advocated that the heterogeneity of ARDS can be tangled by a precision approach, which identifies endotypes of ARDS; i.e., subtypes characterized by a distinct biological profile that might share mortality risk, clinical course, or treatment responsiveness.
Notwithstanding their contributions, current research efforts on endotyping ARDS might be limited by the fact that they are based on the current conceptual framework of the syndrome, which has been widely questioned. Indeed, for reasons such as high interobserver variability of radiological criteria of ARDS and exclusion of patients requiring high-flow nasal oxygen, influential experts have even suggested to completely abandon the term.
Objective:
Accordingly, in the current study, we attempt to perform endotyping of critically ill patients presenting in the emergency department with de novo AHRF, which is a simpler and more reliable phenotype than ARDS. The approach for endotyping will be dynamic rather than static; i.e, two blood samples with a 24-hour interval will be used for endotyping to trace trajectories of biomarkers (over 1500 unique human proteins). In addition, we attempt to identify what clinical, radiological, physiological and biological variables collected early in the course of AHRF correlate with subsequent mortality and/or persistent severe hypoxemia.
Thus, the research protocol is organized as 3 aims.
Aim#1 will organize a registry and biobank of critically ill patients presenting in the emergency department with de novo AHRF.
Aim#2 will build a predictive model to identify what variables among those collected in Aim#1 are associated with subsequent mortality and/or persistent severe hypoxemia.
Aim#3 will use an agnostic discovery approach to explore novel proteomic biomarkers-based dynamic endotypes in critically ill patients presenting in the emergency department with de novo AHRF. Also, Aim#3 will create a multiprotein model of biomarkers associated with subsequent mortality and/or persistent severe hypoxemia and will determine whether inclusion of this multiprotein panel in the predictive score developed in Aim#2 improves risk prediction.
1,369 studies on the registry are indexed under Respiratory Insufficiency; 264 are open to participants now.
This study's planned enrollment of 350 is above the median of 100 across 455 observational studies indexed under Respiratory Insufficiency.
Browse Respiratory Insufficiency studies →Evangelismos Hospital is the lead sponsor of 29 studies on the registry; 6 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Patients presenting in the emergency department with de novo acute hypoxemic respiratory failure
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
We will consider for inclusion patients presenting in the emergency department with de novo acute hypoxemic respiratory failure (AHRF). De novo AHRF is defined as the requirement of oxygen flow rate of 5 liters per minute or more to maintain SpO2 of 90% or more in a patient who does not receive long term oxygen therapy.
Identification of dynamic endotypes of acute hypoxemic respiratory failure
Mutually exclusive subgroups of patients (clusters) characterized by a distinct biological profile that might share mortality risk, clinical course, and/or treatment responsiveness.
Time frame: Until death or hospital discharge, assessed up to 28 days following presentation to the emergency department
All-cause mortality
To determine what variables among those collected, including protein biomarkers, are associated with subsequent all-cause mortality.
Time frame: Until death or hospital discharge, assessed up to 28 days following presentation to the emergency department
Persistent severe hypoxemia
To determine what variables among those collected, including protein biomarkers, are associated with persistent severe hypoxemia. We will consider that persistent severe hypoxemia is present in endotracheally intubated individuals receiving positive pressure ventilation and having a PaO2:FiO2 ratio of equal to or less than 100 mmHg at 48 hours following intubation.
Time frame: Until 28 days following presentation to emergency department
Intensive care unit-free days
Intensive care unit-free days are calculated by the number of days in the first 28 days following presentation in the emergency department that a patient is alive and not in the intensive care unit.
Time frame: Until 28 days following presentation to emergency department
Vasopressor-free days
Vasopressor-free days are calculated by the number of days in the first 28 days following presentation in the emergency department that a patient is alive and not receiving vasopressors.
Time frame: Until 28 days following presentation to emergency department
Ventilator-free days
Ventilator-free days are calculated by the number of days in the first 28 days following presentation in the emergency department that a patient is alive and not on a ventilator.
Time frame: Until 28 days following presentation to emergency department
Continuous renal replacement therapy-free days
Continuous renal replacement therapy-free days are calculated by the number of days in the first 28 days following presentation in the emergency department that a patient is alive and not receiving continuous renal replacement therapy.
Time frame: Until 28 days following presentation to emergency department
Bacteremia
Bacteremia is determined by a positive blood culture.
Time frame: Until 28 days following presentation to emergency department
Plan to share: Yes
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: Within 3 months from publication
Access criteria: For research use
Started Dec 2021 (actual). Primary completion is estimated for Apr 2028, 76 months after the start.
Of 232 non-industry observational studies under Respiratory Insufficiency, half reached primary completion within 22 months of starting (the median), counting those still running; a quarter within 12 and three quarters within 54. This study's planned 76 months is above that.
Counting every sponsor, half of 248 studies reached it within 22 months; a quarter within 12 and three quarters within 44.
How these figures are worked out, and which studies are left out of them.
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Evangelismos Hospital