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Lung Injury clinical trials

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NCT ID: NCT04607434 Completed - Immunosuppression Clinical Trials

Mechanism of Delayed Neutrophil Apoptosis in Acute Lung Injury

Start date: January 1, 2021
Phase:
Study type: Observational

Literature basis Acute respiratory distress syndrome (ARDS) is a clinical syndrome characterized by respiratory distress and progressive hypoxemia, which is caused by diffuse alveolar and pulmonary interstitial edema caused by various pulmonary and extrapulmonary factors other than cardiogenic factors. ARDS incidence rate is as high as 75 /10 000 per year, and sepsis and pulmonary infection are the most common causes. In the past, it was generally believed that excessive immune activation is the core of the pathophysiology of ARDS, and neutrophils are recognized as the core driver of inflammatory hyperactivity and lung injury in ARDS. Although some progress has been made in the epidemiology, pathogenesis and pathophysiology of ARDS in the past 50 years, and the clinical outcomes of some patients with ARDS have been improved by optimizing the mode of mechanical ventilation and fluid treatment, as well as prone ventilation and the use of muscle relaxants, ARDS is still one of the most common causes of death and disability in intensive care units, The mortality rate of the disease is currently as high as 30-40%. There is still a lack of effective drugs for the treatment of ARDS in clinic, and even glucocorticoids applied for immune overactivation have not achieved good results. This is related to the unclear pathogenesis of ARDS. Therefore, it is still a hot and difficult point to further explore the pathogenesis and progression of ARDS and find new therapeutic targets. In the past, mature PMN in peripheral blood was generally considered as a functional cell in the end stage, but it is widely involved in different innate immune responses (including inflammation, infection, tumor, autoimmunity, etc.) and can adopt very different effector mechanisms. Therefore, with the deepening of research, neutrophil subtypes with different functions (such as immune regulation and repair) have been identified in recent years: cd16dimcd62lbrightpmn and cd16brightcd62ldimmpmn. In the steady state of healthy people, the classic mature neutrophils (cd16brightcd62lbright) in peripheral blood account for more than 98% of the total PMN, and the proportion of the two neutrophil subtypes is relatively low. In the inflammatory state, the proportion of cd16dimcd62lbright and cd16brightcd62ldim neutrophils increased significantly. Proteomic analysis showed that there were significant differences between the two subtypes of neutrophils. The nucleus of cd16dimcd62lbright neutrophil subgroup is banded, which is released from bone marrow after being stimulated by lipopolysaccharide (LPS). It accounts for 20% - 25% of PMN in whole blood in LPS infection model. The apoptosis rate is significantly reduced, and the bacteriostatic effects such as oxidative burst and phagocytosis are significantly enhanced; On the contrary, cd16brightcd62ldim neutrophil subgroup has reduced antibacterial ability and shows immunosuppressive phenotype. It is a newly discovered neutrophil subtype with immunosuppressive function in recent years, which can inhibit T cell proliferation, which is related to immunosuppression in the experimental human endotoxemia model. In our previous studies, we have successfully obtained a new amino acid derivative of ocotillol ginsenoside, which may have the pharmacological activities of ocotillol ginsenoside and glycine, and has a potential role in improving the delay of apoptosis and immunosuppression of ARDS neutrophil subtypes, and has the potential of new drug development for the treatment of ARDS. The experimental steps are as follows: Firstly, the peripheral blood of ARDS patients in ICU was collected, and neutrophils were isolated from the peripheral blood. The proportion of neutrophil subtypes and the degree of apoptosis were detected by flow cytometry. Co culture with human T lymphocytes in vitro to observe its ability to inhibit T cell proliferation. Then, the neutrophils of ARDS patients were cultured with different doses of ginsenoside glycine derivatives, and the detection of the above indexes was repeated again. Finally, the mechanism of neutrophils in the pathogenesis and progression of ARDS was discussed.

NCT ID: NCT04574869 Withdrawn - COVID-19 Clinical Trials

A Study of RLS-0071 in Patients With Acute Lung Injury Due to COVID-19 Pneumonia in Early Respiratory Failure

Start date: January 2021
Phase: Phase 1
Study type: Interventional

The aim of this study will test the safety, tolerability, and efficacy of RLS-0071 for approximately 28 days in comparison to a placebo control in patients with acute lung injury due to COVID-19 pneumonia in early respiratory failure. Patients will be randomized and double-blinded for two parts, a single-ascending dose (SAD) part and a multiple-ascending dose (MAD) part. The name of the study drug involved in this study is: RLS-0071.

NCT ID: NCT04546919 Recruiting - Clinical trials for Acute Respiratory Distress Syndrome (ARDS)

Effect of R-spondin3 on Sepsis Induced Endothelial Dysfunction

Start date: July 8, 2020
Phase:
Study type: Observational

Sepsis is the most frequent risk factor for ALI/ARDS. Meanwhile, Pulmonary is the most vulnerable organ to fail in response to sepsis, vascular endothelial dysfunction is a central event in the pathophysiology of sepsis. An improved understanding of endothelial response and associated biomarkers may lead to strategies to more accurately predict outcome and develop novel endothelium-directed therapies in sepsis. The human and mouse R-spondins encode a family of proteins that includes four paralogs (R-spo1-4). R-spondins are secreted proteins found primarily in the extracellular region and are known to promote β-catenin signaling. Among them, the embryonic lethal vascular remodeling phenotype of R-spondin3 (Rspo3) mutant mice suggests a role of EC derived Rspo3 in angiogenesis. Rspo3 protects tissues against mesenteric I/R by tightening endothelial cell junction and improving vascular intergrity. However, the role of Rspo3 in sepsis-induced pulmonary endothelial dysfunction remains unclear. Thus, it is worthwhile to explore the relationship between Rspo3 and sepsis-induced lung injury, which will be helpful for prevention and treatment of sepsis-induced lung injury and endothelial dysfunction.

NCT ID: NCT04541264 Recruiting - Clinical trials for Early Prediction for Sepsis Induced Acute Lung Injury

Radiomics Markers to Predict Sepsis Induced Acute Respiratory Distress Syndrome

Start date: June 1, 2021
Phase:
Study type: Observational

Introduction: Sepsis-induced acute respiratory distress syndrome(SI-ARDS) is a common complication of severe sepsis and is an independent contributor to poor prognosis of patients. It remains a clinical challenge to identify the SI-ARDS early and accurately, which could optimize the treatment strategy and reduce the mortality risk. Radiomics high-dimensional features extracted from CT images offer an insight into microvascular damage of SI-ARDS that are imperceptible to human eyes and aspects of intra-alveolar heterogeneity with potential prognostic relevance. Methods: Study design Investigators screened all patients with sepsis and septic shock who are treated in Sun Yat-sen Memorial Hospital, Sun Yat-sen University during the period from 1 May 2015 and 30 May 2022. Patients were recruited retrospectively from May 2015 to April 2021 as discovering group, and prospectively during the period from May 2021 to May 2022 as validation group. Follow-up will conducted until April 2023. Cohort descriptions and definitions Investigators plan to recruit 160 patients in discovering group, 40 patients in internal validation group, and 100 patients in external validation group. Patients between 18 and 80 years of age with sepsis and septic shock will be screened for eligibility. SI-ARDS is defined by sequential occurrence of the sepsis-3 consensus criteria for sepsis and the Berlin Definition for ARDS. The exclusion criteria are: 1. admission stay <24hours, 2. the presence of end-stage lung disease or long-term oxygen therapy, 3. critically ill patients who have started mechanical ventilation caused by SI-ARDS before admission, 4. a history of lung transplantation and chronic obstructive pulmonary disease, 5. cancer patients not/have received chemotherapy. Outcome measures In this study, the primary outcome measure was the occurrence rates of acute respiratory distress syndrome(ARDS). It refers to the occurrence of sepsis patients progressed into ARDS. Secondary outcome measures were as follows: 1.28-day mortality 2.ventilator-free days 3.respiratory failure-free days Data collection All clinical data were collected by investigators and trained personnel. Each participant's data will be filled in electronic case report forms (CRF) and store online using REDCap (Research Electronic Data Capture). Discussion: SI-ARDS is one common severe complication with critically ill sepsis patients, which causes high mortality and poor prognosis. Early ARDS patient(arterial oxygen tension/inspired oxygen fraction [PaO2/FIO2] ≤ 300 mmHg but > 200 mmHg) may not require invasive mechanical ventilation, and is more readily reversible than acute respiratory distress syndrome(ARDS). In this ambispecive cohort study, investigators developed and validated novel nomograms incorporating the radiomics signature and clinical signature to provide an easy-to-use and individualized prediction of SI-ARDS occurrence and severe degree in patients with early stage.

NCT ID: NCT04541199 Completed - Acute Lung Injury Clinical Trials

Driving Pressures in a Closed-loop and a Conventional Mechanical Ventilation Mode

Start date: August 30, 2019
Phase: N/A
Study type: Interventional

In mechanically ventilated patients, driving pressure (ΔP) assess the strain applied to the respiratory system and is related to ICU mortality. The aim of this randomized cross-over trial was to compare ΔP selected by a closed-loop system and by physician tailored mechanical ventilation mode. Pediatric patients admitted to PICU will be enrolled if they were invasively ventilated without any detectable respiratory effort, hemodynamic instability, or significant leakages. Two 60 minute periods of ventilation determined by randomization in APV-CMV and ASV 1.1 will be compared. Settings were adjusted to reach the same minute ventilation in both modes. ΔP will be calculated as the difference between plateau pressure and total PEEP measured using end-inspiratory and end-expiratory occlusion maneuvers, respectively.

NCT ID: NCT04526912 Terminated - Acute Lung Injury Clinical Trials

Treatment and Prevention of Acute Lung Injury (ALI) in Patients With COVID-19 Infection

ALI
Start date: August 28, 2020
Phase: Phase 1
Study type: Interventional

The study aims to assess the potential benefit and evaluate the safety and tolerability of a single subcutaneous (SC) dose of VIB7734 in hospitalized patients with documented infection of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) with pulmonary involvement. Subjects will be administered a single dose of VIB7734 injected under the skin, assessed for efficacy for 28 days and followed for an additional 42 days.

NCT ID: NCT04519606 Completed - Clinical trials for Ventilator-Induced Lung Injury

Respiratory Mechanics During One-lung Ventilation

Start date: December 1, 2020
Phase:
Study type: Observational [Patient Registry]

Intraoperative lung protective ventilatory strategy has been widely recognized to reduce postoperative pulmonary complications in laparotomy and laparoscopic surgeries. However, the clinical evidence and consensus for ventilatory strategy to protect the dependent lung segments during thoracic surgery that requires one-lung ventilation (OLV) is currently not available. Since lung compliance changes significantly during OLV, the levels of respiratory mechanics should be optimized to avoid barotrauma and volutrauma. This study aims to determine the optimal levels of volume-pressure dynamics during OLV and at the phase of recruitment of the independent lungs by achieving optimal lung compliance, gas exchange and hemodynamics.

NCT ID: NCT04511923 Recruiting - Covid19 Clinical Trials

Nebulised Heparin to Reduce COVID-19 Induced Acute Lung Injury

CHARTER-Irl
Start date: December 23, 2020
Phase: Phase 1/Phase 2
Study type: Interventional

The investigators present a randomised open label phase Ib/IIa trial of nebulised unfractionated heparin to evaluate the effect of nebulised unfractionated heparin on the procoagulant response in ICU patients with SARS-CoV-2 requiring advanced respiratory support. As this is one of the first studies of nebulised heparin in COVID 19 lung disease the investigators will assess safety as a co-primary outcome.

NCT ID: NCT04503057 Recruiting - Covid19 Clinical Trials

Exhaled Breath Particles as a Clinical Indicator for Lung Injury and Acute Respiratory Distress Syndrome (ARDS)

Start date: May 1, 2020
Phase:
Study type: Observational [Patient Registry]

Acute Respiratory Distress Syndrome (ARDS) reflects the hallmark of the critical course of coronavirus (COVID19). The investigators have recently shown that Exhaled Breath Particles (EBP) measured as particle flow rate (PFR) from the airways could be used as a noninvasive real-time early detection method for primary graft dysfunction (which bears a pathophysiological resemblance to ARDS) in lung transplant patients. The investigators have also previously demonstrated the utility of PFR in early detection and monitoring of ARDS in a large animal model. PFR has been shown to be elevated prior to the cytokine storm which classically occurs in ARDS. Early detection of ALI and ARDS is intimately linked to a patient's chance of survival as early treatment consisting of the preparation for intensive care, prone positioning and protective mechanical ventilation can be implemented early in the process. In the present study the investigators aim to use real-time PFR as an early detector for COVID19-induced ARDS. The investigators will also collect EBPs onto a membrane for subsequent molecular analysis. Previous studies have shown that most of those proteins found in bronchoalveolar lavage (BAL) can also be detected in EBPs deposited on membranes. The investigators therefore also aim to be able to diagnose COVID19 by analyzing EBPs using Polymerase Chain Reaction (PCR) with the same specificity as PCR from BAL, with the added benefit of being able to identify protein biomarkers for early detection of ARDS.

NCT ID: NCT04499378 Recruiting - Covid19 Clinical Trials

Tomographic Findings in COVID-19 and Influenza H1N1

Start date: August 15, 2020
Phase:
Study type: Observational

The investigators decided to conduct a longitudinal study that compares the pulmonary tomographic patterns found in patients with viral pneumonia (i.e. influenza H1N1 and SARS-CoV-2) at a regional hospital. The primary aim of this study is to evaluate the association between the radiological CT pattern and the need for invasive mechanical ventilation. A secondary aim is to assess the mortality within the first 28 days of intensive care unit admission.