Clinical Research Directory

Early Switch in Moderate ARDS

The optimal timing for transition from controlled to assisted mechanical ventilation in patients with acute respiratory distress syndrome (ARDS) remains uncertain. Excessive spontaneous respiratory effort may promote injurious transpulmonary pressure swings and heterogeneous regional ventilation, whereas unnecessary prolongation of controlled ventilation may increase sedation exposure and diaphragmatic dysfunction. This prospective, single-center physiological interventional study will enroll mechanically ventilated adults with ARDS and a PaO₂/FiO₂ ratio \>100 and ≤200 mmHg, measured during PEEP=5 cmH2O, who are receiving controlled mechanical ventilation. Participants will undergo a protocolized 30-minute transition from controlled to assisted mechanical ventilation after reduction of sedation sufficient to allow spontaneous respiratory activity. Respiratory effort and drive, airway and esophageal pressures, respiratory flow, respiratory mechanics, gas exchange, and regional ventilation measured by electrical impedance tomography will be assessed before and during the transition. Participants will subsequently be followed for 48 hours to determine whether assisted ventilation can be maintained without return to fully controlled mechanical ventilation.

Clinical Trial of CG-BM1 Allogeneic Human Bone Marrow Mesenchymal Stem Cell Injection in the Treatment of Acute Respiratory Distress Syndrome

1. To evaluate the safety and tolerability of CG-BM1 for the treatment of patients with Acute Respiratory Distress Syndrome. 2. To observe the preliminary effectiveness of CG-BM1 in treating Acute Respiratory Distress Syndrome patients.

Right Heart Injury Monitoring on ECMO

This study aims to find out whether it is practical to introduce a consistent monitoring approach to the right side of the heart in patients supported with VV-ECMO. VV-ECMO is a life support machine that takes over the work of the lungs to give them time to recover. It is used when lung injury is life-threatening. Whilst receiving VV-ECMO support, in addition to the current standard of care, the following will be performed twice weekly: * Heart scan (echocardiogram) * Blood tests (hs-troponin and NT-proBNP) The patient's involvement in the study lasts for as long as they are on the life support machine, plus one final heart scan 48 hours after it is removed.

Spontaneous vs Controlled Mechanical Ventilation in Acute Hypoxemic Respiratory Failure

Acute hypoxemic respiratory failure may progress to acute respiratory distress syndrome, a life-threatening condition that often requires mechanical ventilation. The optimal ventilation strategy in this patient population remains uncertain. The SVALBARD trial is a feasibility and pilot study designed to compare spontaneous versus controlled mechanical ventilation in patients with acute hypoxemia respiratory failure. The primary objective is to assess the feasibility of the study procedures and interventions, while also collecting descriptive data on key clinical variables to inform the design of a future randomized controlled trial.

Clinical Evaluation of a Point of Care (POC) Assay to Identify Phenotypes in the Acute Respiratory Distress Syndrome

Patients prospectively classified to the hyper-inflammatory ARDS phenotype on the basis of clinical characteristics and a novel POC biomarker assay will have worse clinical outcomes than the hypo-inflammatory phenotype. Study Aim The purpose of this project is to prospectively identify hyper- and hypo-inflammatory phenotypes in patients with ARDS and determine clinical outcomes associated with each phenotype. The primary objective of this study is to assess the clinical outcomes in patients with ARDS according to their prospectively defined inflammatory phenotype determined using a POC assay. Results of group allocation will be blinded to clinical and research staff until database lock. Secondary Objectives The secondary objectives of this study are to: (i) Assess the agreement of the phenotype allocation using the POC assay and the clinical study dataset. (ii) Assess the stability of phenotype allocation over time (iii) To test feasibility of delivering a POC assay in the NHS intensive care setting.

WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department

The purpose of this clinical trial is to determine the best initial non-invasive respiratory support (NIRS) strategy for adults who present to the emergency department with acute hypoxemic respiratory failure, a condition in which blood oxygen levels are dangerously low and require urgent treatment. This study compares two commonly used non-invasive respiratory support strategies to evaluate their effectiveness and safety, based on important patient outcomes during hospitalization, including survival, the need for invasive mechanical ventilation, and the duration of respiratory support. Participants will be randomly assigned (with an equal chance) to receive one of the following treatments: * Non-Invasive Positive Pressure Ventilation (NIPPV): Oxygen delivered under pressure through a face mask. * High-Flow Nasal Oxygen (HFNO): Oxygen delivered at high-flow through a specially designed nasal cannula placed in the nostrils. Researchers will compare the two treatment strategies using a hierarchical assessment of major pulmonary outcomes, including: * Hospital survival * Days on mechanical ventilation * Duration of non-invasive respiratory support As part of the study, researchers will collect: * Blood and urine samples * Physiologic measurements (such as chest movement measured through sensors placed on the skin) * Information from participants' medical records

Turning Ratios Into Prognosis: Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Powerful Predictors of ARDS in Pediatric Burn Patients: A Prospective Evaluation

The aim of this study is to evaluate the role of Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as predictors for development of ARDS in pediatric burn patients.

Multicentric, Randomized Study to Assess Safety and Efficacy of Centhaquine in Patients With ARDS

Acute respiratory distress syndrome (ARDS) is a life-threatening condition with a diffuse, inflammatory form of lung injury, causing pulmonary infiltration and respiratory failure leading to poor oxygenation. It is a rapidly progressive form of respiratory failure and accounts for approximately 10% of admissions to the intensive care unit (ICU) and has a high mortality (40%) in severe cases. Globally, approximately 3 million ARDS cases are reported each year, with around 200,000 cases seen in the United States. The etiology of ARDS could be pulmonary or extra-pulmonary. Patients with ARDS have symptoms like difficulty in breathing, shortness of breath, and cyanosis, and they may require assisted breathing/ventilatory support/extracorporeal membrane oxygenation. About 25% of ARDS patients need mechanical ventilation to support breathing; however, a ventilator-induced lung injury (VILI) is known to further exacerbate ARDS in many of them. In recent decades, numerous efforts have been made to develop therapies for treating/managing ARDS. Unfortunately, they have been largely unsuccessful or inconclusive, and at present, no effective pharmacological therapy for ARDS is available. Hence, development of better therapeutics for ARDS is an unmet need. Centhaquine is a first-in-class resuscitative agent for hypovolemic shock approved for marketing in India. Centhaquine has been found to be an effective resuscitative agent in rat, rabbit, and swine models of hemorrhagic shock. Its safety and tolerability have been demonstrated in a human phase I study in 25 subjects (CTRI/2014/06/004647). Results from multicentric, randomized, double-blind, parallel, controlled clinical phase II (CTRI/2017/03/008184) and phase III (CTRI/2019/01/017196) studies conducted in India indicate that centhaquine is a novel, first-in-class, highly effective resuscitative agent for hypovolemic shock. A total of 155 patients with hypovolemic shock have been studied in the combined phase II and III trials, while a multicentric phase IV study (NCT05956418) in 400 patients with hypovolemic shock is currently being conducted in India. The outcomes of the completed trials indicate that centhaquine is safe and reduces mortality significantly (P=0.0271) compared to standard treatment of hypovolemic shock. In the phase II and III studies, ARDS and MODS were evaluated as secondary endpoints. Centhaquine provided hemodynamic stability and significantly reduced ARDS and multiple organ dysfunction score (MODS) in patients enrolled in these trials, which suggests that centhaquine has potential beyond treating hypovolemic shock and could be useful for ARDS treatment. Centhaquine is likely to provide hemodynamic stability, improve tissue oxygenation, reduce pulmonary edema, reduce ARDS score, and reduce MODS in patients with ARDS.

Medical Device Clinical Trial Without CE Marking to Evidence Safety and Performance of the INBENTUS VERSATILE Ventilator in Patients Requiring Assisted/Controlled Mechanical Ventilation and Weaning.

Pre-market clinical trial on 81 aldults participants to evidence safety and performance of the non-CE-marked medical device INBENTUS VERSATILE ventilator. The 81 aldult participants are ventilated between 3 and 48 hours with invasive mechanical ventilation (IMV) in assisted/controlled mode and weaning under partial pressure support or volume support, followed by monitoring period until ICU discharge, hospital discharge or 30 days. The study design differentiates between a Validation Cohort (up to 20 participants) for device validation and a Study Cohort (up to 61 participants) for safety and performance confirmation. Serious Adverse Events related to study device and/or its procedure is defined as the primary safety endpoint, whereas technical failure rate is defined as the primary performance endpoint.

Trunk Inclination, Positive End-expiratory Pressure, and Lung Recruitability

This multicenter, physiological, observational study hypothesizes that in moderate to severe ARDS, trunk inclination unloads the chest wall, but its impact on lung mechanics depends on PEEP levels and lung recruitability.

Dexamethasone Treatment for Sepsis-associated Acute Respiratory Distress Syndrome: a Multicenter, Randomised, Double-blinded, Controlled Trial

Acute respiratory distress syndrome (ARDS) is a major cause of acute hypoxemic respiratory failure in critically ill patients and is associated with substantial mortality. Current management is largely supportive, and no pharmacologic therapy has been shown consistently to reduce mortality in a broad population of patients with ARDS. Inflammation plays a central role in the pathogenesis of ARDS. Excessive inflammatory activation contributes to alveolar-capillary injury, impaired gas exchange, and progression of organ dysfunction. Glucocorticoids may mitigate these processes and have been associated in some studies with improved clinical outcomes, including shorter duration of mechanical ventilation. However, the effect of glucocorticoids on survival remains uncertain. ARDS is a heterogeneous syndrome with diverse etiologies, and treatment response may vary according to the underlying cause. A post hoc analysis of the Dex-ARDS trial suggested that the treatment effect of glucocorticoids may be greater in ARDS caused by pneumonia or extrapulmonary sepsis. In a cross-sectional survey of 135 patients with ARDS from 20 ICUs in China, pneumonia- and extrapulmonary sepsis-associated ARDS accounted for 77.6% of cases, indicating that these are the predominant etiologic subtypes encountered in clinical practice in China. More importantly, compared with ARDS attributable to other causes, pneumonia- and extrapulmonary sepsis-associated ARDS has been associated with higher mortality, suggesting a greater disease burden, worse prognosis, and a more urgent need for improved treatment strategies. On this basis, the present trial will enroll patients with ARDS caused by sepsis, including pneumonia and extrapulmonary sepsis. The primary hypothesis of this study is that, among patients with sepsis-associated ARDS, dexamethasone plus usual care, as compared with placebo plus usual care, will reduce 90-day all-cause mortality. We therefore designed a multicenter, randomized, double-blind, controlled trial to evaluate the clinical efficacy of dexamethasone in patients with sepsis-associated ARDS. The primary objective is to compare dexamethasone plus usual care with placebo plus usual care with respect to 90-day all-cause mortality.

Personalized Ventilator Settings for Patients on ECMO

While mechanical ventilation can be used to sustain life in those with lung injury, it, can further worsen lung injury or prevent lung healing resulting in high morbidity and mortality as seen in Acute Respiratory Distress Syndrome (ARDS). Using extracorporeal membrane oxygenation (ECMO), the highest level of life support also known as the heart-lung machine, investigators may minimize injury from mechanical ventilation to allow the lungs to heal; however, the optimal ventilator strategies while on ECMO are unknown. This study will evaluate personalized ventilator strategy compared to standard of care ventilation.

End-expiratory Transpulmonary Pressure-guided vs Electrical Impedance Tomography-guided PEEP Titration Methods in Patients With Intra-abdominal Hypertension Combined With Acute Respiratory Distress Syndrome: a Randomized Crossover Controlled Study

This study aims to adopt a randomized crossover design to compare the effects of end-expiratory transpulmonary pressure-guided PEEP titration and EIT-guided PEEP titration on local lung ventilation, shunt, dead space, and ventilation-perfusion (V/Q) ratio as monitored by EIT. Additionally, it will evaluate their impact on respiratory mechanics, chest wall mechanics, mechanical power, hemodynamics, gas exchange, intra-abdominal pressure. By identifying an optimal PEEP titration strategy for patients with intra-abdominal hypertension (IAH) and acute respiratory distress syndrome (ARDS), this study aims to develop a mechanical ventilation approach that maintains lung recruitment and minimizes lung injury while avoiding adverse effects on other organs. The findings could facilitate the clinical application of this strategy and benefit a broader population of patients with IAH and ARDS.

Assessment of the PEEP Responsiveness to Titrate End-expiratory Pressure and of the Need for Muscle Relaxation During Prone Positioning in Moderate-to-severe Acute Respiratory Distress Syndrome: A Master Protocol

Despite best supportive care, mortality of the Acute Respiratory Distress Syndrom (ARDS) remains high. In the absence of specific treatments, providing safe and efficient mechanical ventilation (MV) is key to survival. The use of low tidal volumes (VT) and plateau pressures (PPLAT) improves survival in randomized controlled trials (RCTs), but the safest VT to be applied for each patient remains unknown. Whether targeting low ∆P instead of a 6 mL/kg VT improves outcome has not been tested prospectively. The optimal method to set PEEP is also a matter of debate. As the amount of potentially recruitable lung vary widely among patients and is strongly associated with the response to PEEP, it may be necessary to tailor PEEP settings based on the response to a PEEP trial. The first aim is to test a personalized approach to set PEEP widely supported by the literature. The first hypothesis is that i) patients with greater amounts of recruitable lung may benefit from higher PEEP levels, provided that attention is paid to maintain ∆P below 14 cmH2O, ii) setting PEEP based on results of a PEEP-responsiveness test improves survival as compared to low- and high-PEEP strategies applied independently of the patient response. Apart from VT reduction and PPLAT control below 30 cmH2O, only 2 interventions demonstrated a reduction of mortality in large RCTs: a 48-hour continuous infusion of neuromuscular blocking agents (NMBAs) at the acute phase of ARDS6 and the use of prone positioning (PP). Whereas there is little doubt on the utility of PP in patients with PaO2/FiO2 ratio \< 150 mmHg, there is more controversy on the impact of NMBAs on survival. Despite a strong rationale and a very widespread use in clinical practice, no current guidelines answer the question of the best timing of muscle relaxation in moderate to severe ARDS patients treated with PP. As a second aim, the hypothesis is that the early systematic and combined use of NMBAs improved survival of patients with moderate to severe ARDS requiring prone positioning after optimization of PEEP settings.

Early EIT-Guided PEEP Titration on Pulmonary Physiology in Patients With Moderate-to-Severe ARDS Undergoing Prone Positioning (EIT-PEEP-PRONE)

Background: Electrical impedance tomography (EIT)-guided PEEP titration has been shown to improve regional ventilation distribution, increase respiratory system compliance, and reduce mechanical power in patients with acute respiratory distress syndrome (ARDS), but its effect on mortality remains unproven. In patients with moderate-to-severe ARDS, prone positioning for 4 hours allows pulmonary ventilation and perfusion to reach a new steady state, with optimization of ventilation-perfusion (V/Q) matching and other pulmonary physiological parameters. However, whether dynamic PEEP titration guided by EIT at this time point can further optimize V/Q matching and other pulmonary physiological parameters compared with conventional methods has not been reported. Objective: To investigate whether EIT-guided PEEP titration performed at 4 hours after prone positioning initiation can further optimize V/Q matching and other pulmonary physiological parameters in patients with moderate-to-severe ARDS undergoing prone positioning. Methods: This is a prospective, single-center, randomized, open-label, parallel-controlled physiological study. A total of 40 patients with moderate-to-severe ARDS (Berlin definition, PaO₂/FiO₂ \< 150 mmHg) will be enrolled and randomized in a 1:1 ratio to either the EIT-guided group or the control group. PEEP intervention will be performed at 4 hours after prone positioning initiation (T1) in both groups: the EIT group receives EIT-guided PEEP titration, while the control group receives PEEP set according to the ARDSNet/PEEP-FiO₂ table. The primary outcome is V/Q matching percentage assessed by EIT at 18 hours of prone positioning (T2) and 6 hours after supine repositioning (T3). Secondary outcomes include respiratory mechanics, EIT-derived parameters (regional ventilation distribution, global inhomogeneity index, center of ventilation), oxygenation indices, echocardiographic measures of cardiac function, and clinical outcomes (28-day mortality, ventilator-free days, ICU length of stay, etc.). Conclusion: This study will provide physiological evidence for early EIT-guided PEEP titration in patients with moderate-to-severe ARDS undergoing prone positioning, and will lay the foundation for future large-scale clinical trials.

Pediatric Acute Respiratory Distress Syndrome (ARDS) Management Trial

Acute respiratory distress syndrome (ARDS) is a serious and potentially life-threatening lung condition that can affect children. Currently, ventilator settings commonly used in treatment are based on approaches developed for adults, and it remains unclear whether these settings are equally effective for children. Because children's bodies respond differently than adults', it is important to determine the most effective ventilator strategies specifically for pediatric patients. This study will compare two different ventilator approaches in children with ARDS to identify which method provides the greatest benefit. The findings will also help inform the design of a larger study in the future.

Machine Learning Prediction of Mortality After Prone Positioning in ARDS

Acute respiratory distress syndrome (ARDS) is a life-threatening condition with high mortality. Prone position ventilation (PPV) is an evidence-based therapy that improves oxygenation and survival in patients with moderate to severe ARDS; however, outcomes remain heterogeneous. Early identification of patients at high risk of mortality after PPV may improve clinical decision-making and individualized management. This retrospective observational study developed and validated a machine learning model to predict intensive care unit (ICU) mortality in patients with ARDS receiving prone position ventilation. Clinical, laboratory, and treatment variables obtained from ICU electronic medical records were used to construct prediction models using multiple machine learning algorithms. The performance of these models was evaluated and compared to identify the optimal model for mortality prediction.

A Trial of Staff Time With Proned Patients in the ICU Using the 'BathMat'

Proning is a way of helping people who are very sick and have trouble breathing. It involves lying patients on their front to get more oxygen into their body. This process happens in a part of the hospital called the Intensive Care Unit, and can last up to 16 hours per day. When in this position, doctors need to turn the patients' head and move their arms every 2-4 hours. Doctors call this repositioning. It helps prevent sores as well as other injuries. To do this, the health care team slide the patient up the bed, so that their (supported) head hangs over the end of the mattress. The head is then turned before the patient is slid back down the bed; their arms are then moved into a different position. This is currently performed by a team of 5+ staff and takes lots of time and resources. The process is also potentially dangerous because it requires a lot of movement which can hurt patients or staff. To make repositioning easier and safer, a group of doctors and engineers have created a new device. It is like a cushion that goes under the patient and inflates. This allows staff to reposition patients without needing to slide the patient on the bed. This also reduces the number of staff needed and lowers the risk to patients and staff. Feedback from staff, patients and the public are being used to help improve the system. To see if the new device works well in other hospitals, the investigators are planning to do a study with 30 patients in up to 4 different hospitals. This will last 14 months, and they will collect information on how well it performs. They will ask patients if they want to take part and will collect feedback after they leave hospital. During the study, staff from each hospital will monitor the device to make sure it is safe and record how useful it is. Any problems will be recorded, and staff will be asked for their opinions on how it affects their work. As well as monitoring safety, they will record the time saving achieved. This is important as it allows repositioning more often, which may reduce pressure sores. It also allows staff to spend more time focusing on other patients and important tasks. To share the results with other doctors, the researchers will write reports and give presentations. If successful, they will start making and selling the device to help sick patients on Intensive Care.

Electrical Impedance Tomography-Guided Identification of the Optimal Lateral Position in Postoperative ARDS

This prospective, randomized crossover physiological study evaluates the effects of lateral positioning (left lateral position and right lateral position) versus the supine position on ventilation-perfusion (V/Q) matching in adult postoperative abdominal surgery participants with acute respiratory distress syndrome (ARDS). Bedside electrical impedance tomography (EIT) will be used to quantify regional ventilation and perfusion (perfusion derived from an intravenous tracer bolus administered during a brief breath-hold) and to calculate global "normal V/Q" (normal V/Q, %). Oxygenation, respiratory mechanics (when applicable), and hemodynamics will be recorded concurrently. Feasibility and safety of the positioning protocol will also be assessed.

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.

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.

Immune Mechanisms and ECMO Strategies for Moderate-to-Severe ARDS

Acute respiratory distress syndrome (ARDS) poses a major threat to human health. Despite extracorporeal membrane oxygenation (ECMO) support, mortality among patients with ARDS remains high due to severe complications and suboptimal mechanical ventilation strategies. Elucidating the mechanisms underlying ECMO-related complications and lung injury repair, and establishing a precision intervention pathway covering the entire course of ECMO management, are urgent unmet needs for improving outcomes in ARDS patients and addressing major public health challenges. This project focuses on five key scientific questions: 1. How can moderate-to-severe ARDS be classified into distinct clinical-immune phenotypes, and what are the optimal therapeutic targets for each phenotype? 2. What are the molecular mechanisms underlying severe complications in ARDS patients receiving ECMO support? 3. Which key immune biomarkers are associated with clinical benefit from awake ECMO? 4. How should mechanical ventilation strategies be optimized in moderate-to-severe ARDS patients supported with ECMO? 5. How can a comprehensive, full-cycle ECMO management pathway be established for patients with moderate-to-severe ARDS? The project consists of five interrelated subprojects: Subproject 1. Construction of Clinical-Immune Phenotypes and Identification of Therapeutic Targets in Moderate-to-Severe ARDS Clinical phenotypes and longitudinal multidimensional biospecimens collected throughout the disease course in moderate-to-severe ARDS patients, including those receiving ECMO support, will be analyzed to characterize the heterogeneity and spatiotemporal interactions of inflammatory and immune cell subsets and to identify effective therapeutic targets. Subproject 2. Mechanisms and Interventions for Immune Dysregulation Underlying Severe ECMO-Related Complications This subproject aims to elucidate the inflammatory and immune mechanisms responsible for major complications occurring in ARDS patients receiving ECMO support. Major complications of interest include acute kidney injury, bleeding and thrombosis, and infection. Subproject 3. Development and Validation of a Clinical-Immune Phenotype-Guided Decision System for Awake ECMO By integrating multidimensional data, a comprehensive ARDS phenotyping framework will be established to identify patients most likely to benefit from awake ECMO. A clinical decision-making system will be developed and subsequently validated through multicenter studies to assess its effectiveness. Subproject 4. Molecular Mechanisms of Lung Repair and Optimization of Mechanical Ventilation During ECMO Support This subproject will investigate the lung-protective effects of different invasive mechanical ventilation strategies and ventilation parameters during ECMO support. Multi-omics analyses of ARDS biospecimens will be performed to elucidate the mechanisms through which lung rest promotes tissue repair and recovery. Subproject 5. Establishment and Evaluation of a Full-Cycle ECMO Management Strategy for Moderate-to-Severe ARDS Based on evidence-based medicine and multidisciplinary collaboration, a comprehensive ECMO management pathway covering the entire disease course will be developed for patients with moderate-to-severe ARDS. Real-world studies will be conducted to evaluate its clinical effectiveness and facilitate continuous optimization. Overall, this project aims to provide mechanistic insights into immune dysregulation, ECMO-related complications, and lung repair, while establishing a precision, full-cycle ECMO management framework to improve outcomes in patients with moderate-to-severe ARDS.\*\*