Clinical Research Directory

Study of the Immunological Pathophysiological Mechanisms Associated With Acute Respiratory Distress Syndrome

About 10% of patients admitted to the ICU suffer from ARDS, with a mortality rate of around 35-45%. The lack of therapeutic innovation in ARDS can be partly explained by the heterogeneity of patients included under this definition. A better understanding of the pathophysiological mechanisms underlying the different patient phenotypes is essential to develop new therapeutic strategies. Objectives: To characterize the inflammatory profile of patients with ARDS using circulating biomarkers and single-cell RNA sequencing of pulmonary immune cells. The investigators hypothesize that there is a correlation between the profile of serum biomarkers (inflammatory sub-phenotypes), the transcriptome of pulmonary immune cells. Briefly the experimental scheme is as follow: * Population: patients with ARDS under invasive mechanical ventilation in the ICU. * Intervention: 1. Determination of the inflammatory subphenotype on circulatory inflammatory biomarkers. 2. Characterization of inflammation by single cell RNA sequencing on lung immune cells collected on broncho-alveolar fluid.

Promoting Change in Practice for Respiratory Failure

Approximately 300,000 Hispanic individuals experience respiratory failure each year in the U.S. Hispanic patients are twice as likely to die from respiratory failure as non-Hispanic patients. There is an urgent need to identify and remediate mechanisms that increase risk of death from respiratory failure. The team's preliminary work identified two potential mechanisms: Hispanic patients with respiratory failure are more likely to be deeply sedated and less likely to receive physical therapy than non-Hispanic patients, which are both associated with mortality and poor long-term functional outcomes. The overall objective of this proposal is to improve outcomes for patients with respiratory failure through changes in intensive care unit (ICU) practice. This trial will refine and pilot an intervention to promote guideline-concordant care. The team's preliminary intervention will be iteratively refined through patient, family, and clinician engagement and piloted at two U.S. ICUs. The outcome of this study will be an intervention aimed at reducing mortality from respiratory failure.

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.

Study of Nogapendekin Alfa Inbakicept and iNKT Cells in Critically Ill Adults With Severe Community-Acquired Pneumonia

This is a Phase 3, randomized, blinded, and placebo-controlled clinical trial investigating a new combination treatment for critically ill adults who have severe community-acquired pneumonia, especially if they also have sepsis or acute respiratory distress syndrome. The study aims to determine if adding the experimental agents, Nogapendekin Alfa Inbakicept and iNKT cells, to standard medical care can reduce the 28-day all-cause mortality rate compared to standard care alone with a placebo.

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.

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.

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.

Pirfenidone to Prevent Fibrosis in Ards.

Acute respiratory distress syndrome (ARDS) is a severe form of acute lung injury and a major cause of Intensive Care Unit (ICU) admission worldwide. Despite a large number of randomized clinical trials, a specific and effective pharmacological approach for patients with ARDS is still lacking. Fibroproliferation is a crucial part of the host defence response, and severe fibrotic lung disease affects ARDS patients even years after acute phase resolution. Pirfenidone is an oral anti-fibrotic drug, approved and largely used for treatment of idiopathic pulmonary fibrosis (IPF). The effect of Pirfenidone in ARDS has been evaluated only in animal models. This is a randomized controlled study to evaluate for the first time the efficacy of Pirfenidone in ARDS.

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.

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

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.

Ultraprotective Lung Ventilation With Respiratory Extracorporeal Life Support for ARDS

Acute respiratory distress syndrome (ARDS) accounts for approximately 10% of all ICU admissions and 23% of patients requiring mechanical ventilation (MV). Despite advances in care, hospital mortality remains high, ranging from 34% in mild cases to 46% in severe ARDS. Positive-pressure MV remains the cornerstone of ARDS management. However, when excessive stress and strain are applied to the lung parenchyma, it can exacerbate lung injury, leading to ventilator-induced lung injury (VILI). VILI substantially contributes to morbidity and mortality in ARDS. Strategies that reduce tidal volume (Vt), driving pressure (ΔP, defined as plateau pressure minus PEEP), and respiratory rate (RR) can lower the mechanical power (PowerRS), i.e., the energy delivered to the lungs by the ventilator. This reduction in pulmonary stress and strain may lessen VILI and potentially improve survival. Nonetheless, reducing Vt to \<6 ml/kg in order to achieve plateau pressures \<23-25 cm H₂O, driving pressures \<9-11 cm H₂O, and RR \<15-20/min can result in severe hypercapnia. This, in turn, may increase intracranial pressure, promote pulmonary hypertension, impair myocardial contractility, reduce renal perfusion, and trigger endogenous catecholamine release. Thus, such "ultraprotective" MV strategies are not feasible for most ARDS patients managed with conventional ventilation. The neutral findings of the REST trial further suggested that low-flow extracorporeal CO₂ removal (ECCO₂R) devices may provide insufficient CO₂ clearance to enable ultraprotective ventilation while adequately controlling respiratory acidosis. Moreover, since partial lung derecruitment may occur with substantial Vt reduction, extracorporeal membrane oxygenation (ECMO) may be necessary, particularly in patients with PaO₂/FiO₂ \<120-130 at the time of Vt reduction. Therefore, respiratory extracorporeal life support (ECLS)-ranging from high-flow ECCO₂R to mid-flow venovenous ECMO (VV-ECMO)-can be employed in this setting. These modalities facilitate further reductions in ventilatory intensity while ensuring adequate oxygenation and CO₂ removal.

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.

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.

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.

Relationship Between the Level of Positive End-expiratory Pressure and Venous Congestion During Acute Respiratory Distress Syndrome.

The main objective is to assess the effect of increased PEEP on echo-Doppler venous congestion in ARDS patients at two PEEP levels, by grading congestion in each venous flow (suprahepatic, renal, portal) as "absent," "moderate," or "severe," and also calculating the VExUS score.

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 aims to develop and validate a machine learning model to predict intensive care unit (ICU) mortality in ARDS patients receiving prone position ventilation. Clinical, laboratory, and treatment variables collected from ICU electronic medical records will be used to construct prediction models using multiple machine learning algorithms. The performance of these models will be evaluated and compared to identify the optimal model for mortality prediction.

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.

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.

Evaluating Artificial Intelligence-Based Clinical Decision Support for Sepsis and ARDS

Sepsis and acute respiratory distress syndrome (ARDS) are common in intensive care units. Managing sepsis and ARDS is inherently complex and requires making numerous decisions under uncertainty. Artificial intelligence (AI) clinical decision support systems (CDSSs) offer a promising approach to support care management for sepsis and ARDS. The goal of this randomized, survey-based study is to compare treatment recommendations enacted by clinicians to those generated by an AI CDSS. The study will investigate whether an AI CDSS can generate treatment recommendations that are safe, appropriate, and indistinguishable to those provided by real clinicians. In this study, participants (i.e., critical care clinicians) will review a series of critical care cases (vignettes) in an electronic survey. Each vignette will contain a de-identified case of a patient with sepsis and ARDS as well as treatment recommendations for the case. Participants will assess the safety and appropriateness of each treatment recommendations and answer whether they think the treatment recommendations came from the clinician or an AI CDSS.

Multi-Omics Integrative Analysis of Serum and Sputum to Uncover Key Determinants of Prognosis in Patients With ARDS

This study is a prospective observational investigation designed to systematically characterize key microbial signatures, metabolite profiles, and gene-expression features in serum and sputum from patients with acute respiratory distress syndrome (ARDS), and to evaluate their associations with response to invasive mechanical ventilation and clinical outcomes. A total of 411 adult ARDS patients meeting the Berlin definition and receiving invasive mechanical ventilation will be enrolled; individuals with significant pre-existing pulmonary disease or a history of immunosuppression will be excluded. Blood and sputum specimens will undergo high-throughput sequencing and metabolomics, including 16S rRNA-based microbiome profiling, whole-transcriptome RNA sequencing, and targeted/untargeted metabolite quantification by LC-MS/MS. Ventilator-related parameters (e.g., tidal volume, positive end-expiratory pressure \[PEEP\], and respiratory system compliance) and clinical endpoints (e.g., 28-day mortality) will be integrated to establish a comprehensive multi-omics analytical framework. Data preprocessing will include batch-effect correction, normalization, and multiple-testing adjustment with false discovery rate control (FDR \< 0.05). Differential microbes, metabolites, and transcripts will be functionally interpreted using KEGG pathway and Gene Ontology (GO) enrichment analyses. Spearman correlation analyses will be performed to examine associations between omics features and ventilator parameters. Key features will be selected using LASSO regression, followed by development of random forest and support vector machine (SVM) models to predict mechanical ventilation response and the risk of ventilator-induced lung injury (VILI). Model performance will be assessed using ROC curves, area under the curve (AUC), calibration plots, and decision curve analysis. By integrating serum and sputum multi-omics data, this study aims to identify molecular biomarkers that influence the effectiveness of mechanical ventilation and prognosis in ARDS, thereby providing evidence to support precision ventilatory strategies and individualized clinical management to improve patient outcomes. The findings are expected to deepen mechanistic understanding of ARDS pathobiology and lay a foundation for future development of multi-omics-guided diagnostic and therapeutic approaches.

Application of Electrical Impedance Tomography in Evaluating Pulmonary Function Improvement After High Lateral Recumbent Position Therapy in ARDS Patients

This randomized controlled trial investigates the effects of prone positioning versus lateral positioning at different angles (30°, 90°, 120°) on pulmonary function improvement in patients with acute respiratory distress syndrome (ARDS). Utilizing electrical impedance tomography (EIT) technology, the study monitors key parameters including ventilation distribution and ventilation-perfusion matching in real time, while integrating respiratory mechanics and blood gas analysis data to comprehensively evaluate the therapeutic efficacy of positional adjustments. The study hypothesizes that high-angle lateral positioning may reduce adverse complications associated with prone positioning while effectively improving oxygenation and pulmonary function. The ultimate objective is to provide a safer and more personalized positional therapy regimen for clinical practice, optimizing ARDS treatment strategies to reduce mortality and enhance patient survival outcomes.

A Study on the Treatment of Patients With Acute Lung Injury Caused by Sepsis Through Microbiota Transplantation

Sepsis is a systemic inflammatory response syndrome triggered by infection, and it is a common critical illness in clinical practice, often leading to multiple organ dysfunction. Among these, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are among the most severe complications. The mortality rate of sepsis-related lung injury is extremely high, reaching 30% - 50%. The existing treatment methods are unable to effectively reduce the high mortality rate of sepsis-related lung injury, and there are no specific treatment measures targeting lung injury itself. Dysbiosis of the intestinal flora plays an important role in the occurrence and development of sepsis-related lung injury. Fecal microbiota transplantation (FMT), as an effective means of regulating the intestinal flora, has shown certain therapeutic potential in some clinical studies. However, current research on FMT for treating sepsis-related lung injury is still in its infancy, and its mechanism is not yet fully clear. The clinical efficacy and safety also lack high-quality evidence support. Therefore, conducting this project's research will provide theoretical basis for targeted microecological treatment of sepsis-related lung injury; establishing a new strategy of combined microbiota transplantation technology for treating patients with sepsis ALI, and providing new ideas and methods for clinical treatment.

Clinical Trial With Aprotinin in the Acute Respiratory Distress Syndrome Treatment

This is a multicentre, double-blind, placebo-controlled Phase III randomized clinical trial designed to evaluate the efficacy and safety of inhaled aprotinin in adult patients with moderate or severe acute respiratory distress syndrome (ARDS). A total of 156 critically ill patients admitted to intensive care units will be randomized to receive either inhaled aprotinin or placebo in addition to standard supportive care. The primary objective is to determine whether aprotinin improves clinical outcomes based on a composite endpoint of mortality and ventilator-free days at 28 days.