Netosis in Determination of Respiratory Infection Severity (NETMINDERS)

Netosis in Mechanically Ventilated ICU Patients in Determination of Respiratory Infection Severity

The study aims to evaluate the prognostic value of alveolar and blood NETosis in patients under mechanical ventilation and treated for an acute low-respiratory tract infection. The main outcome is the occurrence of an acute respiratory distress syndrome (ARDS) according to the Berlin definition.

Study Overview

• Status: Completed
• Conditions: Respiratory Infection
• Intervention / Treatment: Biological: Blood sampling; Procedure: Bronchoalveolar lavage

Detailed Description

Neutrophils are the first line of defense against infectious injury. Among the numerous mechanisms involving the immune system, neutrophil extracellular traps (NETs) have been recently described as an additional way neutrophils are able to use to fight against bacteria. NETs are made of DNA and antimicrobial proteins. In the other hand, NETs promote coagulation and may contribute to evolution of severe pneumonia into acute respiratory distress syndrome.

The secondary objectives of the study include the research of the relation between blood NETosis and alveolar NETosis with:

• the documentation of invasive pulmonary infection based on microbiological analysis criteria (which would be bacteria or viral) of LBA at admission to ICU;
• the diagnosis value of usually used biomarkers: procalcitonin and C-reactive protein;
• marbrure score at admission to ICU;
• arterial lactatemia;
• scores of gravity at admission IGSII and SOFA;
• all-cause mortality at day-28;
• duration of mechanical ventilation at day-28;
• duration of amines at day-28;
• developement of hemodynamic failure;
• developement of pulmonary circulatory failure.

The study will include 1) 60 patients under mechanical ventilation admitted to the intensive care unit for acute respiratory failure, 2) 10 control patients admitted to the ICU after a planned vascular surgery and 3) 10 healthy subjects.

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

• Study Contact: Name: Edouard JULLIEN, MD; Phone Number: +33 1 49095603; Email: edouard.jullien@aphp.fr
• Study Contact Backup: Name: Guillaume Geri, MD, PhD; Phone Number: +33 1 49095601; Email: guillaume.geri@aphp.fr

Study Locations

• France
  • Boulogne-Billancourt, France, 92100
    • Service de médecine intensive réanimation, Hôpital Ambroise Paré, APHP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

• Adult ICU patients under mechanical ventilation with suspected lower-respiratory tract infection;
• Adult ICU patients followed vascular surgical intervention;
• Healthy Volunteers.

Description

Inclusion criteria:

A/ For all subjets:

• Be >/= 18 years of age on day of signing informed consent;
• Affiliated to the french social security - welfare system in France.

B/ Inclusion criteria for acute respiratory failure patients:

admitted to the ICU for acute respiratory failure requiring mechanical ventilation within the first 24 hours after admission and suspected to suffer from an infectious pneumonia, according to the following criteria:

• recent fever;
• acute respiratory failure signs (dyspnea, polypnea > 30 cycles/min, hypoxemia PaO2<65 mmHg);
• pulmonary focal signs of auscultation;
• evocative signs in chest radiography or chest TDM.

C/ Inclusion criteria for control patients:

- admitted to the ICU for post-operative management of vascular surgery.

Exclusion Criteria:

A/ For all subjets:

• pregnancy,
• nosocomial pneumonia,
• no social health insurance,
• neutropenia of any cause;
• patient refusal.

B/ Exclusion criteria for acute respiratory failure patients:

- no mechanical ventilation within the first 24 hours after admission to the ICU.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
acute respiratory failure group; 60 patients under mechanical ventilation admitted to the intensive care unit for acute respiratory failure	Biological: Blood sampling; Blood sampling at baseline and at day-3 (10 ml, EDTA tube), test of NETs.; Procedure: Bronchoalveolar lavage; Bronchoalveolar lavage at admission to the ICU with analysis of cytological, bacteriological, viral and anatomopathological, and test of NETs.
vascular surgery control group; 10 control patients admitted to the ICU after a planned vascular surgery	Biological: Blood sampling; Blood sampling at baseline and at day-3 (10 ml, EDTA tube), test of NETs.
Healthy volunteers group; 10 healthy subjects.	Biological: Blood sampling; Blood sampling at baseline and at day-3 (10 ml, EDTA tube), test of NETs.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute respiratory distress syndrome occurrence	Acute respiratory distress syndrome occurrence according to the Berlin definition within the first 7 days after ICU admission	at day-7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Vital statue of patient	At day-28
Duration of mechanical ventilation	Duration of mechanical ventilation: number of days without mechanical ventilation.	At day-28
IGSII score	IGSII score	At admission to ICU
SOFA score	SOFA score	At admission to ICU
Hemodynamic failure	Development of a hemodynamic failure	At day-28
Pulmonary circulation failure	Development of a pulmonary circulation failure (acute pulmonary heart disease, right ventricle failure)	At day-28

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Edouard JULLIEN, MD, Service de médecine intensive réanimation, Hôpital Ambroise Paré, APHP; Study Director: Guillaume Geri, MD, PhD, Service de médecine intensive réanimation, Hôpital Ambroise Paré, APHP

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2022
• Primary Completion (Actual): January 3, 2023
• Study Completion (Actual): January 3, 2023

Study Registration Dates

• First Submitted: March 20, 2020
• First Submitted That Met QC Criteria: March 20, 2020
• First Posted (Actual): March 24, 2020

Study Record Updates

• Last Update Posted (Actual): March 16, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: mechanical ventilation; pneumonia; acute respiratory distress syndrome; adult ICU; neutrophil extracellular traps (NETs); Netosis; neutrophils
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Disease Attributes; Infections; Communicable Diseases; Respiratory Tract Infections; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Dimercaprol
• Other Study ID Numbers: 2020-A00217-32

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No