Acute Hypoxemic Respiratory FailureEPIPHANYNCT05150483
EndotyPIng PreHospitAl de Novo Acute hYpoxemic Respiratory Failure
An observational study of Acute Hypoxemic Respiratory Failure and Acute Respiratory Distress Syndrome, run by Evangelismos Hospital at 1 site in Greece.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Hypoxemic Respiratory Failure, Acute Respiratory Distress Syndrome
- How many people
- 350 participants
- Where
- 1 siteGreece
- Study dates
- 10 Dec 2021to 20 Jul 2028
- How long will I take part?
- 28 Days
- Phase
- Observational
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients presenting in the emergency department with de novo acute hypoxemic respiratory failure
Who may be able to join
- Adult patients (aged >18 years) presenting in the emergency department
- De novo acute hypoxemic respiratory failure (requiring oxygen flow rate of 5 liters per minute or more to maintain SpO2 of 90% or more)
Who cannot join
- Age <18 years
- Not admitted to the hospital
- Postoperative acute respiratory failure (within one week from surgery)
- Chronic hypoxemic respiratory failure (requiring long term oxygen therapy at home)
- Hypercapnic respiratory failure
- Transferred from another hospital or facility
Show all 9Show fewer
- Pregnant women
- Admitted to the hospital purely to facilitate comfort care
- Lack of informed consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Greece1 site, 1 recruiting
- Recruiting
Evangelismos Hospital
Athens, Attica, 10676
Eleni Papoutsi, MD
About this study
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.
Read the detailed description
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.
- Keywords
- critical illness, intensive care unit, endotypes, phenotypes, emergency department, trajectory, mechanical ventilation, elderly, ageing
- Medical subject headings
- Respiratory Insufficiency, Respiratory Distress Syndrome, Critical Illness, Emergencies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients with de novo acute hypoxemic respiratory failure | 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Until death or hospital discharge, assessed up to 28 days following presentation to the emergency department
Secondary outcomes (7)
All-cause mortality
To determine what variables among those collected, including protein biomarkers, are associated with subsequent all-cause mortality.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Until 28 days following presentation to emergency department
Bacteremia
Bacteremia is determined by a positive blood culture.
Measured: Until 28 days following presentation to emergency department
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2021
- Study start10 Dec 2021
- Primary completion10 Apr 2028 (estimated)
- Study completion20 Jul 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Acute Hypoxemic Respiratory FailureStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 350 participants (estimated)
- Target duration
- 28 Days
Sponsor and investigators
- Lead sponsor
- Evangelismos Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ilias Siempos, Evangelismos Hospital
- Investigators
- Ilias I. Siempos, MD, DSc, Principal investigator, Evangelismos Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05150483
- Sponsor's protocol ID
- 80-1/15.10.2020
- Acronym
- EPIPHANY
- Status last verified
- Sep 2026
- First submitted
- 22 Nov 2021
- Last updated
- 15 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
Meyer NJ, Gattinoni L, Calfee CS. Acute respiratory distress syndrome. Lancet. 2021 Aug 14;398(10300):622-637. doi: 10.1016/S0140-6736(21)00439-6. Epub 2021 Jul 1.
PubMed 34217425Beitler JR, Thompson BT, Baron RM, Bastarache JA, Denlinger LC, Esserman L, Gong MN, LaVange LM, Lewis RJ, Marshall JC, Martin TR, McAuley DF, Meyer NJ, Moss M, Reineck LA, Rubin E, Schmidt EP, Standiford TJ, Ware LB, Wong HR, Aggarwal NR, Calfee CS. Advancing precision medicine for acute respiratory distress syndrome. Lancet Respir Med. 2022 Jan;10(1):107-120. doi: 10.1016/S2213-2600(21)00157-0. Epub 2021 Jul 23.
PubMed 34310901Gattinoni L, Marini JJ. Isn't it time to abandon ARDS? The COVID-19 lesson. Crit Care. 2021 Sep 6;25(1):326. doi: 10.1186/s13054-021-03748-6. No abstract available.
PubMed 34488807Matthay MA, McAuley DF, Ware LB. Clinical trials in acute respiratory distress syndrome: challenges and opportunities. Lancet Respir Med. 2017 Jun;5(6):524-534. doi: 10.1016/S2213-2600(17)30188-1. Epub 2017 May 26.
PubMed 28664851Schenck EJ, Oromendia C, Torres LK, Berlin DA, Choi AMK, Siempos II. Rapidly Improving ARDS in Therapeutic Randomized Controlled Trials. Chest. 2019 Mar;155(3):474-482. doi: 10.1016/j.chest.2018.09.031. Epub 2018 Oct 22.
PubMed 30359616Sanchez E, Price DR, Chung KP, Oromendia C, Choi AMK, Schenck EJ, Siempos II. Persistent severe acute respiratory distress syndrome for the prognostic enrichment of trials. PLoS One. 2020 Jan 27;15(1):e0227346. doi: 10.1371/journal.pone.0227346. eCollection 2020.
PubMed 31986174Harrington JS, Schenck EJ, Oromendia C, Choi AMK, Siempos II. Acute respiratory distress syndrome without identifiable risk factors: A secondary analysis of the ARDS network trials. J Crit Care. 2018 Oct;47:49-54. doi: 10.1016/j.jcrc.2018.06.002. Epub 2018 Jun 2.
PubMed 29898428Price DR, Hoffman KL, Oromendia C, Torres LK, Schenck EJ, Choi ME, Choi AMK, Baron RM, Huh JW, Siempos II. Effect of Neutropenic Critical Illness on Development and Prognosis of Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2021 Feb 15;203(4):504-508. doi: 10.1164/rccm.202003-0753LE. No abstract available.
PubMed 32986956
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- EndotyPIng PreHospitAl de Novo Acute hYpoxemic Respiratory Failure
- ClinicalTrials.gov ID
- NCT05150483
- Acronym / sponsor ID
- EPIPHANY / 80-1/15.10.2020
- Keywords
- critical illness, intensive care unit, endotypes, phenotypes, emergency department, trajectory, mechanical ventilation, elderly
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 350 participants (estimated)
- Lead sponsor
- Evangelismos HospitalUniversity, hospital or other
- Study start
- 10 Dec 2021 (actual)
- Primary completion
- 10 Apr 2028 (estimated)
- Study completion
- 20 Jul 2028 (estimated)
- First posted
- 9 Dec 2021 (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.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Target follow-up
- 28 Days
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with de novo acute hypoxemic respiratory failure | – | –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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients presenting in the emergency department with de novo acute hypoxemic respiratory failure
Key inclusion criteria (2 listed)
- Adult patients (aged >18 years) presenting in the emergency department
- De novo acute hypoxemic respiratory failure (requiring oxygen flow rate of 5 liters per minute or more to maintain SpO2 of 90% or more)
Key exclusion criteria (9 listed)
- Age <18 years
- Not admitted to the hospital
- Postoperative acute respiratory failure (within one week from surgery)
- Chronic hypoxemic respiratory failure (requiring long term oxygen therapy at home)
- Hypercapnic respiratory failure
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Identification of dynamic endotypes of acute hypoxemic respiratory failure
Time frame: Until death or hospital discharge, assessed up to 28 days following presentation to the emergency department
Mutually exclusive subgroups of patients (clusters) characterized by a distinct biological profile that might share mortality risk, clinical course, and/or treatment responsiveness.
7 secondary outcomes
All-cause mortality
Time frame: Until death or hospital discharge, assessed up to 28 days following presentation to the emergency department
Persistent severe hypoxemia
Time frame: Until 28 days following presentation to emergency department
Intensive care unit-free days
Time frame: Until 28 days following presentation to emergency department
Vasopressor-free days
Time frame: Until 28 days following presentation to emergency department
Ventilator-free days
Time frame: Until 28 days following presentation to emergency department
Continuous renal replacement therapy-free days
Time frame: Until 28 days following presentation to emergency department
Bacteremia
Time frame: Until 28 days following presentation to emergency department
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 Sep 2026.
- Background: PubMed 34217425Meyer NJ, Gattinoni L, Calfee CS. Acute respiratory distress syndrome. Lancet. 2021 Aug 14;398(10300):622-637. doi: 10.1016/S0140-6736(21)00439-6. Epub 2021 Jul 1.
- Background: PubMed 34310901Beitler JR, Thompson BT, Baron RM, Bastarache JA, Denlinger LC, Esserman L, Gong MN, LaVange LM, Lewis RJ, Marshall JC, Martin TR, McAuley DF, Meyer NJ, Moss M, Reineck LA, Rubin E, Schmidt EP, Standiford TJ, Ware LB, Wong HR, Aggarwal NR, Calfee CS. Advancing precision medicine for acute respiratory distress syndrome. Lancet Respir Med. 2022 Jan;10(1):107-120. doi: 10.1016/S2213-2600(21)00157-0. Epub 2021 Jul 23.
- Background: PubMed 34488807Gattinoni L, Marini JJ. Isn't it time to abandon ARDS? The COVID-19 lesson. Crit Care. 2021 Sep 6;25(1):326. doi: 10.1186/s13054-021-03748-6. No abstract available.
- Background: PubMed 28664851Matthay MA, McAuley DF, Ware LB. Clinical trials in acute respiratory distress syndrome: challenges and opportunities. Lancet Respir Med. 2017 Jun;5(6):524-534. doi: 10.1016/S2213-2600(17)30188-1. Epub 2017 May 26.
- Background: PubMed 30359616Schenck EJ, Oromendia C, Torres LK, Berlin DA, Choi AMK, Siempos II. Rapidly Improving ARDS in Therapeutic Randomized Controlled Trials. Chest. 2019 Mar;155(3):474-482. doi: 10.1016/j.chest.2018.09.031. Epub 2018 Oct 22.
- Background: PubMed 31986174Sanchez E, Price DR, Chung KP, Oromendia C, Choi AMK, Schenck EJ, Siempos II. Persistent severe acute respiratory distress syndrome for the prognostic enrichment of trials. PLoS One. 2020 Jan 27;15(1):e0227346. doi: 10.1371/journal.pone.0227346. eCollection 2020.
- Background: PubMed 29898428Harrington JS, Schenck EJ, Oromendia C, Choi AMK, Siempos II. Acute respiratory distress syndrome without identifiable risk factors: A secondary analysis of the ARDS network trials. J Crit Care. 2018 Oct;47:49-54. doi: 10.1016/j.jcrc.2018.06.002. Epub 2018 Jun 2.
- Background: PubMed 32986956Price DR, Hoffman KL, Oromendia C, Torres LK, Schenck EJ, Choi ME, Choi AMK, Baron RM, Huh JW, Siempos II. Effect of Neutropenic Critical Illness on Development and Prognosis of Acute Respiratory Distress Syndrome. Am J Respir Crit Care Med. 2021 Feb 15;203(4):504-508. doi: 10.1164/rccm.202003-0753LE. No abstract available.
- Individual participant dataSharing planned: Yes
Related trials for Acute Hypoxemic Respiratory Failure
Recruiting
WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department
Acute Hypoxic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)
Recruiting
Bedside Spirometry for Acute Lung Injury
Respiratory Insufficiency
Recruiting
Spontaneous vs Controlled Mechanical Ventilation in Acute Hypoxemic Respiratory Failure
Acute Respiratory Distress Syndrome (ARDS), Acute Hypoxemic Respiratory Failure
RecruitingObservational study
Brain-lung Interaction During Acute Respiratory Failure
Acute Respiratory Failure
RecruitingPhase 2
Interleukin-6 Guided Treatment With Dexamethasone or Tocilizumab in Patients Hospitalized With Acute Respiratory Symptoms - a Feasibility Study
Acute Hypoxemic Respiratory Failure
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.
Ilias I. Siempos, MD, DSc principal investigator
Evangelismos Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Hypoxemic Respiratory Failure and Acute Respiratory Distress Syndrome, run by Evangelismos Hospital at 1 site in Greece.
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 2 inclusion and 9 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 Sep 2026. 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 Greece. 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 Eleni D. Papoutsi, MD (+306981173761, helenapapoutsi@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of dynamic endotypes of acute hypoxemic respiratory failure (time frame: Until death or hospital discharge, assessed up to 28 days following presentation to the emergency department). 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 NCT05150483, which also lists 8 linked publications.
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 Sep 2026.