Clinical Research Directory

JUST BREATHE, Breathing Life Into Innovative Therapies for ARDS (Master Record)

This is a Phase 2 multicenter, randomized, double-blinded, placebo-controlled study that will evaluate the safety and efficacy of host-directed therapeutics in hospitalized adults diagnosed with Acute Respiratory Distress Syndrome (ARDS) utilizing a platform trial design. Participants will be randomized to receive either a placebo or one of the active treatments. This record describes the default procedures and analyses for all cohorts. Each specific cohort may have additional eligibility requirements, safety and efficacy procedures, or endpoints, which will be described in the corresponding intervention-specific records on clinicaltrials.gov listed below in the detailed description.

JUST BREATHE, Breathing Life Into Innovative Therapies for ARDS- Cohort B: Paridiprubart

This is a Phase 2 multicenter, randomized, double-blinded, placebo-controlled study that will evaluate the safety and efficacy of host-directed therapeutics in hospitalized adults diagnosed with Acute Respiratory Distress Syndrome (ARDS) utilizing a platform trial design. Cohort B: Participants will be randomized to receive either a placebo or paridiprubart. This record describes the default procedures and analyses for Cohort B. Please see NCT06703073 for information on the BP-ARDS-P2-001 Master Protocol.

JUST BREATHE, Breathing Life Into Innovative Therapies for ARDS- Cohort C: Bevacizumab

This is a Phase 2 multicenter, randomized, double-blinded, placebo-controlled study that will evaluate the safety and efficacy of host-directed therapeutics in hospitalized adults diagnosed with Acute Respiratory Distress Syndrome (ARDS) utilizing a platform trial design. Cohort C: Participants will be randomized to receive either a placebo or bevacizumab. This record describes the default procedures and analyses for Cohort C. Please see NCT06703073 for information on the BP-ARDS-P2-001 Master Protocol.

JUST BREATHE, Breathing Life Into Innovative Therapies for ARDS- Cohort A: Vilobelimab

This is a Phase 2 multicenter, randomized, double-blinded, placebo-controlled study that will evaluate the safety and efficacy of host-directed therapeutics in hospitalized adults diagnosed with Acute Respiratory Distress Syndrome (ARDS) utilizing a platform trial design. Cohort A: Participants will be randomized to receive either a placebo or vilobelimab. This record describes the default procedures and analyses for Cohort A. Please see NCT06703073 for information on the BP-ARDS-P2-001 Master Protocol.

Clinical Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of HT31-1 for Treating ARDS

This Phase 1/2A, randomized, double-blind study will evaluate the safety, tolerability, and pharmacokinetics (PK) of HT31-1 (hCitH3-mAb) in healthy adult volunteers and in patients with mild-to-moderate acute respiratory distress syndrome (ARDS) due to an infectious source. The current trial (Part A) focuses on single ascending doses (SAD) in healthy volunteers to characterize the safety profile, PK parameters, and immunogenicity of HT31-1. Emerging data from this phase will inform dose selection for the subsequent Part B study in ARDS patients and help establish the recommended Phase 2 dose (RP2D). Additionally, exploratory pharmacodynamic and biomarker assessments will be performed to evaluate target engagement and potential early biological activity.

Effect of EIT-guided PEEP in ARDS Patients With Higher Recruitability

Acute respiratory syndrome distress (ARDS) is a clinical common syndrome with high mortality. Mechanical ventilation (MV) is the cornerstone of management of ARDS but can lead to ventilator-induced lung injury. Positive end-expiratory pressure (PEEP), as one of main component of MV, has been widely used in the clinical practice. However, the PEEP selection is still a difficult problem for moderate to severe ARDS patients. EIT, an imaging tool evaluating the regional ventilation distribution at the bedside, can achieve the individual PEEP selection for all mechanically ventilated patients. Our previous study found that moderate to severe ARDS patients with higher recruitability could benefit from EIT-guided PEEP. This article compared the effect of PEEP titrated guided by EIT with fraction of inspired oxygen (FiO2)-PEEP table on the clinical outcomes in patients with higher recruitability.

Comparative Analysis of Salivary and Bronchoalveolar Lavage IL-6 and TNF-α as Biomarkers in Pediatric Acute Respiratory Distress Syndrome

The aim of this study is to determine the degree of agreement in cytokines level measured through BAL and those measured through salivary glands excretion. and to compare the validity of cytokines in BAL versus salivary secretion in predicting the stage of ARDS and disease outcome in term of mortality, disease progression and length of stay.

Prone Position Assessed by 3D EIT

To investigate global and regional changes in lung ventilation and perfusion induced by prone position in ARDS patients assessed by 3D-EIT. And to investigate the difference between 2D-EIT and 3D-EIT in prone position monitoring.

The Caribbean Registry of Extracorporeal Membrane Oxygenation (ECMO) From the University Hospital in Martinique

The project's main goal is to collect baseline clinical and procedural data as well as to assess clinical outcomes for all patients undergoing VV, VA or VAV ECMO implantation in the French West Indies and Guiana. All patients undergoing ECMO implantation will be prospectively registered.

Cyclic On-off Switching of Pulmonary Blood Flow in Moderate to Severe ARDS

Although the theoretical model of "cyclic on-off switching of pulmonary blood flow" provides a crucial perspective for understanding VILI, its clinical validation and real-time intervention face significant obstacles. The fundamental reason lies in the lack of pulmonary microcirculation monitoring technology capable of bedside, non-invasive, continuous operation with sufficient spatiotemporal resolution. Nowadays, a novel 3D-EIT can perform real-time and non-invasive assessment of the distribution of pulmonary blood flow. However, if 3D-EIT can help to identify "cyclic on-off switching of pulmonary blood flow" is still unclear.

Lung EIT Image Guide Ventilation in ARDS

The goal of this multi-center randomized controlled clinical trial is to learn if an individualized, bedside electrical impedance tomography (EIT)-guided ventilation strategy (including EIT-guided prone positioning and PEEP titration) can improve outcomes compared with a conventional lung-protective ventilation strategy in adult patients with acute respiratory distress syndrome (ARDS). The main questions it aims to answer are: Does the individualized EIT-guided ventilation strategy reduce 28-day mortality in ARDS patients? Researchers will compare the EIT-guided intervention arm to a control arm receiving routine lung-protective ventilation (without bedside EIT guidance) to see if the EIT-guided approach lowers 28-day mortality and improves other clinical outcomes. Adult ARDS patients who meet inclusion criteria will be assigned to EIT-guided group and control group through stratified randomization: EIT-guided group: Undergo bedside EIT assessments using a China-manufactured EIT device to guide decisions about prone positioning and individualized PEEP titration (including a recruitment maneuver). Control group: Receive PEEP setting per conventional PEEP-FiO₂ tables and prone positioning per standard clinical indications without EIT guidance. Both groups: Receive standard supportive ICU care and routine outcome assessments at multiple time points. Primary outcome: 28-day mortality. Other outcomes include ventilator-free days to day 28 and so on.

Real-Time Algorithm-Driven Ventilation Feedback to Improve Lung-Protective Ventilation in Critically Ill Patients

The REALVENT trial is designed to evaluate whether a real-time, algorithm-driven ventilation feedback strategy can improve lung-protective ventilation (LPV) achievement rates in critically ill patients receiving invasive mechanical ventilation. This multicentre randomised controlled trial will compare real-time respiratory waveform monitoring with automated feedback against standard ICU care. The primary endpoint is the LPV achievement rate over the first 72 hours.

Early Biological and Mechanical Profiling in Sepsis-Associated ARDS

Sepsis-associated acute respiratory distress syndrome (ARDS) is one of the deadliest and most biologically heterogeneous forms of respiratory failure. Despite uniform diagnostic criteria, patients with septic ARDS show wide variability in inflammatory intensity, alveolar epithelial and endothelial injury, alveolar fluid composition, ventilatory mechanical properties, and clinical evolution. Early identification of these differences may enable better prognostication and more precise treatment. This prospective observational study aims to deeply characterize the earliest phases of septic ARDS by integrating serial bronchoalveolar lavage (BAL) at 0, 24 and 72 hours with parallel plasma biomarker profiling and detailed mechanical ventilation data. This design captures the evolving biological and physiological landscape of septic ARDS during its most dynamic window. The central goal is to identify systemic, alveolar, and hybrid bio-mechano-inflammatory subphenotypes that can inform personalized approaches to support, risk stratification, and future interventional trials.

Free for Weaning ECMO vs Respiratory Driven Study

In its most severe form, Acute Respiratory Distress Syndrome (ARDS) may require the use of veno-venous ECMO (vvECMO). While the criteria for vvECMO indication, ECMO settings, and ventilator management are relatively well-defined after the publication of the EOLIA trial and subsequent national or international guidelines, few studies have assessed the criteria and methods for weaning from vvECMO. Besides, advances in the understanding of the pathophysiology of mechanical ventilation (MV) weaning process have led to the development of specific monitoring tools for this phase. Schematically, respiratory drive can be evaluated via the ventilator by measuring the pressure generated during a 100-millisecond expiratory occlusion (P0.1) and respiratory efforts through the measurement of esophageal pressure variation (delta Poeso). Recent retrospective studies conducted on COVID-19 ARDS patients supported by vvECMO suggest a longer duration of mechanical ventilation for patients whose weaning and decannulation process was "forced," i.e., performed under conditions of significant respiratory drive and effort. High values of P0.1 and delta Poeso were associated with prolonged MV duration. Self-inflicted lung injury (P-SILI) and elevated transpulmonary pressure related to these uncontrolled respiratory efforts likely explain the negative impact on MV duration. Therefore, this randomized study proposes to assess these monitoring tools, which are regularly used in clinical practice, to guide vvECMO weaning and decannulation decisions.

The Impact of Low Versus High Positive End-expiratory Pressure on Diaphragm Function, Ventilation Efficiency, and Lung Mechanics

The goal of this interventional study is to evaluate the effect of different positive end-expiratory pressures (PEEP) on lung and diaphragm function in patients mechanically ventilated with pressure support ventilation in the intensive care unit. The main questions aim to answer: Does higher PEEP level affect diaphragm contractions and ventilatory efficiency? Does higher PEEP level limit inspiratory efforts? Does higher PEEP level affect lung compliance? The participants will be subjected to three different PEEP levels during pressure support ventilation: Low PEEP (4 cmH2O), Medium PEEP (10 cmH2O), High PEEP (16 cmH2O). The lung and diaphragm function will be evaluated using high-resolution esophageal manometry, electrical activity of the diaphragm, external diaphragm ultrasound and spirometric ventilator data.

A Real World Study of Respiratory Critical Disease.

Acute Respiratory Distress Syndrome (ARDS) is a form of acute diffuse lung injury caused by various etiologies, which rapidly progresses to acute respiratory failure. It is characterized by a sudden onset and severe clinical course. Globally, ARDS affects approximately 3 million individuals each year, accounting for about 10% of admissions to intensive care units (ICUs). Due to the lack of specific pharmacological therapies, mechanical ventilation remains the mainstay of treatment. Therefore, identifying and analyzing prognostic factors for ARDS patients is of great significance for improving patient outcomes and reducing the incidence of poor prognosis.

Lung Injury is One of the Primary Causes of Morbidity and Mortality in Critically Ill Patients. These Patients Will be Monitored for: 1) Immune Cell Activation 2) Blood-based Biomarkers. In Vitro Models Derived From These Samples Will be Treated With Novel Agent PIP-2 to Evaluate Its Efficacy.

Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) is a condition where high levels of inflammation damage the lung. This is a highly morbid condition with no specific pharmacologic therapies. The investigators posit that ARDS is caused due to an exaggerated activation of immune cells and that blockade of this activation may reduce lung damage/injury and help in ARDS management and possibly recovery. To test this hypothesis, the investigators propose to generate an in vitro immune cell model and test a novel (reactive oxygen species) blocking agent PIP-2 on this model. The investigating team will obtain blood of ARDS patients and isolate immune cells (specifically peripheral blood mononuclear cells or PBMC) and monitor the activation of these cells and their blockade by PIP-2. This is entirely an in vitro study.

RECOMMEND Platform Trial

The goal of this platform trial is to determine the efficacy, safety and cost-effectiveness of various interventions in patients with acute cardiorespiratory failure requiring extracorporeal membrane oxygenation (ECMO) The main question the platform trial aims to address is to determine the effect of a range of interventions on survival, organ support and resource utilisation to day 28 for hospitalised patients receiving ECMO. Researchers will compare various interventions within multiple platform trial domains to see if the interventions have effects on survival, organ support and resource utilisation for the patient cohort. Participants will be enrolled in accordance with the platform trial's domain structure to answer the research questions.

Ciprofol's Impact on Oxygenator Function in Extracorporeal Membrane Oxygenation (ECMO) Patients

This study evaluates the safety and effectiveness of Ciprofol, a new sedative, in critically ill patients receiving Extracorporeal Membrane Oxygenation (ECMO), a life-support system for heart or lung failure. The investigation aims to: Assess how Ciprofol affects the oxygenator, a critical ECMO component responsible for adding oxygen to blood. Compare the safety of Ciprofol to midazolam, a commonly used sedative. Eligibility Criteria Adults aged 18 years or older. Patients receiving ECMO and mechanical ventilation for over 72 hours. Individuals requiring sedation for medical procedures. Study Protocol Participants will be randomly assigned to one of two groups: Ciprofol Group: Initial sedation dose of 0.1 mg/kg, adjusted as needed. Midazolam Group: Initial sedation dose of 0.05 mg/kg, adjusted as needed. Both groups will receive pain management with remifentanil. Sedation levels will be adjusted daily by the clinical team to ensure patient safety and comfort. Outcome Measures Primary: Oxygenator performance (oxygen and carbon dioxide levels) on Days 3 and 7. Secondary: Changes in blood triglyceride and clotting marker (D-dimer) levels, oxygenator lifespan before replacement, and safety outcomes such as low blood pressure, respiratory issues, or allergic reactions. Significance ECMO patients often require prolonged sedation, but current sedatives like midazolam may contribute to oxygenator damage. Ciprofol's potential for faster recovery and fewer side effects could improve sedation practices and device longevity in this high-risk population.

Pleural Strain by Speckle-Tracking Ultrasound: Feasibility and Driving Pressure Associations

What is this study about? This research aims to test a new ultrasound technology called "speckle tracking" to measure how much the lining of your lungs (pleura) stretches during breathing, especially if you're on a breathing machine (ventilator). Doctors want to see if this technology can help them adjust ventilator settings more safely, reducing the risk of lung damage. Why is this important? Lung protection: Patients on ventilators, especially those with severe lung problems (like ARDS or pneumonia), need careful settings. Too much pressure from the ventilator can harm the lungs. Better monitoring: Current tools can't easily measure lung stretching at the bedside. This ultrasound method might offer a simple, painless way to check lung health in real time. Who can join? Included: Adults (18+ years) in the ICU with serious illness (assessed by a standard score called APACHE II \>8), whether on a ventilator or not. Excluded: People with recent chest surgery, broken ribs, nerve/muscle diseases, or pregnancy (to avoid risks and ensure accurate measurements). What will happen during the study? Ultrasound scans: A small probe will be placed gently on your chest for 5-10 minutes. The machine will record videos of your lung movements during breathing. This is painless and uses no radiation. Measurements: Doctors will repeat the scan twice (10 minutes apart) to check consistency. For ventilator patients, scans will be done at different pressure settings to see how lung stretching changes. How will this help me or others? Direct benefit: You'll receive detailed monitoring of your lung function, which may help doctors personalize your care. Future benefit: If successful, this technology could help doctors worldwide adjust ventilators more safely, reducing complications for ICU patients. Is my information safe? All data (scans, medical records) will be anonymized and stored securely. Participation is voluntary, and you can withdraw anytime without affecting your treatment. Who is conducting the study? Led by Dr. Xu Qiancheng and the ICU team at Yijishan Hospital, Wannan Medical College. Experts in ultrasound and critical care will ensure the study is safe and scientifically rigorous.

International Survey for EXTubation Evaluation and Respiratory Dynamics in Acute Respiratory Distress Syndrome

EXTEND ARDS study is an international survey for ventilator weaning and extubation among ARDS patients. This study will be conducted on behalf of the Japanese ARDS Clinical Practice Guideline 2024 Committee as well as endorsement of the Japanese Society of Intensive Care Medicine, the Japanese Respiratory Society, and the Japanese Society of Respiratory Care Medicine. This survey aims to prospectively collect the clinical data of mechanically ventilated ARDS patients related with ventilator weaning and extubation internationally as well as the outcome of ARDS patients with extubation failure. This study also aims to identify predictive factors strongly associated with extubation failure. The contents of mechanical ventilation settings, respiratory conditions, and blood examination data will be collected.

Effects of Low Tidal Volume and Airway Pressure Release Ventilation on Lung Tissue Mechanics in ARDS Patients Under Mechanical Ventilation: A Prospective Randomized Crossover Study

The goal of this clinical trial is to learn how low tidal volume ventilation (LTV) and airway pressure release ventilation (APRV) affect lung tissue mechanics in adults with ARDS. The main questions it aims to answer are: Does LTV or APRV improve lung tissue mechanics in patients with ARDS under mechanical ventilation? Researchers will compare LTV and APRV to see which ventilation mode works better for improving lung mechanics and patient safety.

EXTEND ARDS-J Esophageal Pressure Study

Background: Acute respiratory distress syndrome (ARDS) patients require careful assessment before extubation to prevent failure, which is associated with poor outcomes. While current guidelines recommend weaning protocols, these are based on general respiratory failure studies rather than ARDS-specific data. Esophageal pressure (Pes) measurement provides direct assessment of inspiratory effort but is rarely utilized clinically. Objectives: This Japanese sub-study of EXTEND ARDS aims to evaluate whether: 1. ΔPes measurements during spontaneous breathing trials (SBT) can predict SBT failure 2. ΔPes measurements post-extubation can predict 48-hour extubation failure Methods: This prospective observational study will be conducted in Japanese ICUs. Esophageal pressure will be measured using standardized Nutrivent balloons (4mL volume) with Hamilton ventilators. Balloon placement in the lower third of the esophagus will be confirmed by cardiac artifacts and chest X-ray. ΔPes will be calculated as the difference between end-expiratory and peak inspiratory esophageal pressure, excluding esophageal contractions. Significance: This study addresses a knowledge gap regarding the utility of esophageal pressure monitoring in ARDS patients during mechanical ventilation weaning. Findings may help optimize extubation timing and improve patient outcomes through objective physiological measurements.

CUrrent Practices of Intensive Care for the Management of Acute Respiratory Distress Syndrome in EurOpe.

This study seeks to gain a comprehensive understanding of current ARDS management practices across European ICUs, with a particular focus on the use of LTV and PP therapy, which have been shown to improve outcomes in ARDS patients. The primary objectives focus on evaluating how LTV and PP are implemented across different institutions, while secondary objectives encompass a broader assessment of other ARDS treatment strategies. These include mechanical ventilation approaches, including PEEP titration, the use of NMBAs, and advanced extra-corporal therapies like ECMO and extracorporeal carbon dioxide removal (ECCO2R). Additionally, the study will explore diagnostic methods and decision-making processes that guide ARDS management in diverse clinical settings.