EndotyPIng PreHospitAl de Novo Acute hYpoxemic Respiratory Failure

Acute Respiratory Distress Syndrome Clinical Trial

— EPIPHANY  

Official title:

EndotyPIng PreHospitAl de Novo Acute hYpoxemic Respiratory Failure

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05150483
• Other study ID #: 80-1/15.10.2020
• Status: Recruiting
• Start date: December 10, 2021
• Est. completion date: April 30, 2024

Study information

• Verified date: February 2024
• Source: Evangelismos Hospital
• Contact: Eleni D. Papoutsi, MD
• Phone: +306981173761
• Email: helenapapoutsi[@]gmail.com
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical 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 subsequent mortality and/or persistent severe hypoxemia.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 250
• Est. completion date: April 30, 2024
• Est. primary completion date: April 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Hypoxemic Respiratory Failure
• Acute Lung Injury
• Acute Respiratory Distress Syndrome
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Respiratory Insufficiency

Locations

Country	Name	City	State
Greece	Evangelismos Hospital	Athens	Attiki

Sponsors (1)

Lead Sponsor	Collaborator
Evangelismos Hospital

Country where clinical trial is conducted

Greece, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Until death or hospital discharge, assessed up to 28 days following presentation to the emergency department
Secondary	All-cause mortality	To determine what variables among those collected, including protein biomarkers, are associated with subsequent all-cause mortality.	Until death or hospital discharge, assessed up to 28 days following presentation to the emergency department
Secondary	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.	Until 28 days following presentation to emergency department
Secondary	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.	Until 28 days following presentation to emergency department
Secondary	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.	Until 28 days following presentation to emergency department
Secondary	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.	Until 28 days following presentation to emergency department
Secondary	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.	Until 28 days following presentation to emergency department
Secondary	Bacteremia	Bacteremia is determined by a positive blood culture.	Until 28 days following presentation to emergency department