Ignite Creation Date:
2025-12-24 @ 5:24 PM
Ignite Modification Date:
2025-12-29 @ 10:20 PM
Study NCT ID:
NCT06444750
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-09-04
First Post:
2024-05-31
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Comparison of the Proteome in ICU Patients in Search for TRALI Biomarkers: A Case-control Study Using Both Retrospective and Prospective Samples
Sponsor:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Organization:
Study Overview
Official Title:
Comparison of the Proteome in ICU Patients in Search for TRALI Biomarkers: A Case-control Study Using Both Retrospective and Prospective Samples
Status:
NOT_YET_RECRUITING
Status Verified Date:
2025-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CURIE
Brief Summary:
Transfusion-related acute lung injury (TRALI) is a severe complication of blood transfusions. After a transfusion, TRALI develops in 0.08-15% of cases depending on the characteristics of the studied population. Due to preventive measures the incidence has decreased. However, the incidence of TRALI is 50-100 times higher in critically ill patients compared to the general hospital population. Since the absolute incidence of respiratory transfusion complications is low and TRALI is under-diagnosed and - reported, to this date is has not been possible to elucidate the exact pathophysiology of TRALI. Consequently, no biomarkers are yet known to detect TRALI. This study aims to identify TRALI biomarkers, gain insight in cellular pathways underlying TRALI development and the role of neutrophils and regulatory T cells, which could enhance transfusion safety.
Detailed Description:
Objective of the study:
* To identify biomarkers specific for TRALI, thus aiding in future diagnostics of TRALI.
* To investigate the proteome in TRALI patients and thus gain knowledge on TRALI pathophysiology. This knowledge can be used to investigate preventive measures and therapy for TRALI.
* To investigate the role of neutrophils and regulatory T cells in TRALI, which are thought to be essential dysregulated in the in TRALI pathogenesis.
Study design:
Case-control study using retrospective and prospective samples. Samples available from known TRALI patients stored at Sanquin Blood Bank will be compared to samples from intensive care patients with acute respiratory distress syndrome (ARDS), pneumonia, or without lung injury and to samples of healthy volunteers. The treating physician will screen ICU patients for eligibility for one of our groups and asks for permission to be approached by a researcher for informed consent. After obtaining informed consent, patients will be allocated to a group depending on whether they need a transfusion. After admission and informed consent extra blood samples (30ml) will be drawn from patients within 24 hours of arrival.
For Group 1 (patients who receive a transfusion but do not have lung injury), Group 2 (patients who receive a transfusion and have indirect ARDS), and Group 3 (patients who receive a transfusion with pneumonia (local lung injury)) a second tube blood sample (30ml) will be drawn 12 hours after the first transfusion. We will collect two samples (max 60 mL) for this group to analyze the effect of transfusion on the proteome. Together with the clinical data we will search for TRALI biomarkers.
Study population:
Adult intensive care patient who are admitted with:
Pneumonia (without ARDS), indirect ARDS or no pulmonary injury with and wihtout receiving a blood transfusion.
Healthy volunteers obtained through the Sanquin donor system. The TRALI samples that are obtained through hemovigilance at Sanquin (see protocol 4.1).
Primary study parameters/outcome of the study:
The primary endpoint of this study is to identify TRALI-specific biomarkers by comparing plasma proteomic profiles between the following groups: TRALI patients, indirect ARDS patients (with and without transfusion), pneumonia patients (with and without transfusion), and healthy volunteers. To isolate the impact of transfusion on the proteome and differentiate it from TRALI-specific changes, we will also analyze proteomic profiles before and after transfusion in relevant groups. This approach aims to increase the specificity and sensitivity of identified protein biomarkers for accurate TRALI diagnosis and facilitate the development of novel diagnostic assays.
Secundary study parameters/outcome of the study (if applicable):
The secundary outcomes of this study are:
1. Characterizing the TRALI Proteome: we will perform in-depth characterization of the proteome in TRALI patients to gain a comprehensive understanding of the molecular mechanisms underlying TRALI pathophysiology. This analysis aims to uncover potential therapeutic targets and pathways involved in TRALI development.
2. Investigating Neutrophil and Treg responses: we will investigate the phenotype, activation status, and functional responses of neutrophils and Tregs in TRALI patients compared to relevant control groups. This detailed analysis will shed light on the roles of neutrophils and Tregs in TRALI pathogenesis.
* To identify biomarkers specific for TRALI, thus aiding in future diagnostics of TRALI.
* To investigate the proteome in TRALI patients and thus gain knowledge on TRALI pathophysiology. This knowledge can be used to investigate preventive measures and therapy for TRALI.
* To investigate the role of neutrophils and regulatory T cells in TRALI, which are thought to be essential dysregulated in the in TRALI pathogenesis.
Study design:
Case-control study using retrospective and prospective samples. Samples available from known TRALI patients stored at Sanquin Blood Bank will be compared to samples from intensive care patients with acute respiratory distress syndrome (ARDS), pneumonia, or without lung injury and to samples of healthy volunteers. The treating physician will screen ICU patients for eligibility for one of our groups and asks for permission to be approached by a researcher for informed consent. After obtaining informed consent, patients will be allocated to a group depending on whether they need a transfusion. After admission and informed consent extra blood samples (30ml) will be drawn from patients within 24 hours of arrival.
For Group 1 (patients who receive a transfusion but do not have lung injury), Group 2 (patients who receive a transfusion and have indirect ARDS), and Group 3 (patients who receive a transfusion with pneumonia (local lung injury)) a second tube blood sample (30ml) will be drawn 12 hours after the first transfusion. We will collect two samples (max 60 mL) for this group to analyze the effect of transfusion on the proteome. Together with the clinical data we will search for TRALI biomarkers.
Study population:
Adult intensive care patient who are admitted with:
Pneumonia (without ARDS), indirect ARDS or no pulmonary injury with and wihtout receiving a blood transfusion.
Healthy volunteers obtained through the Sanquin donor system. The TRALI samples that are obtained through hemovigilance at Sanquin (see protocol 4.1).
Primary study parameters/outcome of the study:
The primary endpoint of this study is to identify TRALI-specific biomarkers by comparing plasma proteomic profiles between the following groups: TRALI patients, indirect ARDS patients (with and without transfusion), pneumonia patients (with and without transfusion), and healthy volunteers. To isolate the impact of transfusion on the proteome and differentiate it from TRALI-specific changes, we will also analyze proteomic profiles before and after transfusion in relevant groups. This approach aims to increase the specificity and sensitivity of identified protein biomarkers for accurate TRALI diagnosis and facilitate the development of novel diagnostic assays.
Secundary study parameters/outcome of the study (if applicable):
The secundary outcomes of this study are:
1. Characterizing the TRALI Proteome: we will perform in-depth characterization of the proteome in TRALI patients to gain a comprehensive understanding of the molecular mechanisms underlying TRALI pathophysiology. This analysis aims to uncover potential therapeutic targets and pathways involved in TRALI development.
2. Investigating Neutrophil and Treg responses: we will investigate the phenotype, activation status, and functional responses of neutrophils and Tregs in TRALI patients compared to relevant control groups. This detailed analysis will shed light on the roles of neutrophils and Tregs in TRALI pathogenesis.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?: