EndotyPIng PreHospitAl de Novo Acute hYpoxemic Respiratory Failure

NCT ID: NCT05150483

Last Updated: 2025-08-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

250 participants

Study Classification

OBSERVATIONAL

Study Start Date

2021-12-10

Study Completion Date

2026-04-30

Brief Summary

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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

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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.

Conditions

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Acute Hypoxemic Respiratory Failure Acute Respiratory Distress Syndrome

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* 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)

Exclusion Criteria

* 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
* Pregnant women
* Admitted to the hospital purely to facilitate comfort care
* Lack of informed consent
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Evangelismos Hospital

OTHER

Sponsor Role lead

Responsible Party

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Ilias Siempos

Assistant Professor in Critical Care and Pulmonary Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ilias I. Siempos, MD, DSc

Role: PRINCIPAL_INVESTIGATOR

Evangelismos Hospital

Locations

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Evangelismos Hospital

Athens, Attica, Greece

Site Status RECRUITING

Countries

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Greece

Central Contacts

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Eleni D. Papoutsi, MD

Role: CONTACT

+306981173761

Facility Contacts

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Eleni Papoutsi, MD

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 34217425 (View on PubMed)

Beitler 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.

Reference Type BACKGROUND
PMID: 34310901 (View on PubMed)

Gattinoni 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.

Reference Type BACKGROUND
PMID: 34488807 (View on PubMed)

Matthay 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.

Reference Type BACKGROUND
PMID: 28664851 (View on PubMed)

Schenck 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.

Reference Type BACKGROUND
PMID: 30359616 (View on PubMed)

Sanchez 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.

Reference Type BACKGROUND
PMID: 31986174 (View on PubMed)

Harrington 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.

Reference Type BACKGROUND
PMID: 29898428 (View on PubMed)

Price 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.

Reference Type BACKGROUND
PMID: 32986956 (View on PubMed)

Other Identifiers

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80-1/15.10.2020

Identifier Type: -

Identifier Source: org_study_id

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