Acute Respiratory Distress Syndrome

Acute respiratory distress syndrome (ARDS) is a common and life-threatening condition in intensive care units, characterized by substantial biological and clinical heterogeneity. Differences in patients' inflammatory responses, baseline immune function, and organ failure patterns contribute to variability in ARDS severity, treatment response, and clinical outcomes. Precision classification of ARDS based on biological and inflammatory characteristics may therefore be essential for improving patient outcomes. Previous analyses of randomized clinical trials have identified two reproducible inflammatory subphenotypes-"hyperinflammatory" and "hypoinflammatory"-which differ in organ dysfunction profiles, clinical trajectories, and responses to treatments such as fluid management strategies, corticosteroids, and ventilatory interventions. However, key uncertainties remain, including whether these inflammatory subphenotypes can be validated in Chinese ARDS populations, how various bedside prediction models perform in identifying these subphenotypes, and whether model-based subphenotype identification can guide individualized treatment decisions. This multicenter cohort study aims to: (1) validate inflammatory subphenotypes of ARDS using latent class analysis; (2) compare the predictive performance of existing bedside models for subphenotype identification; and (3) assess whether subphenotype assignment based on prediction models can guide individualized treatment strategies, including fluid management, PEEP titration, and corticosteroid use. In addition to these primary aims, the study may include other exploratory objectives, such as evaluating subphenotype stability over time, characterizing biological pathways associated with subphenotypes, and assessing additional treatment-response patterns to support future precision ARDS management strategies.

The goal of this interventional study is to compare standard mechanical ventilation to a lung-stress oriented ventilation strategy in patients with Acute Respiratory Distress Syndrome (ARDS). Participants will be ventilated according to one of two different strategies. The main question the study hopes to answer is whether the personalized ventilation strategy helps improve survival.

BTI-203 is a randomized, double-blind, placebo-controlled, multicenter, Phase 2 proof-of-concept (POC) study to evaluate the efficacy and safety of rhu-pGSN plus standard of care (SOC) in subjects with moderate-to-severe ARDS (P/F ratio ≤150) due to pneumonia or other infections. Potential subjects hospitalized with pneumonia or other infections are to be screened within 24 hours of diagnosis of ARDS.

The goal of this clinical trial is to learn if R-3750 is safe in \[in patients with late-stage, non-resolving Acute Respiratory Distress Syndrome (ARDS) . The main question\[s\] it aims to answer are: 1. the favorable safety profile 2. clinical improvement that includes reduced ventilator dependence and improved lung function. Participants will be given oral capsules daily and/or enteral nasogastric or orogastric (NG/OG tube) if necessary.

This study will investigate how different types of routine sedation may affect patient's breathing whilst on a ventilator in the Intensive Care Unit (ICU). There are different approaches to sedation which may have advantages and disadvantages. During the study patients will receive both intravenous and inhaled volatile sedation (similar to anaesthetic 'gases' used for general anaesthesia) and the drive to breath, breathing efforts and function of the lung will be assessed.

The goal of this clinical trial is to learn whether methylprednisolone improves outcomes in critically ill patients with a hyperinflammatory phenotype. It will also evaluate the safety of methylprednisolone at different doses. The main questions it aims to answer are: * Does methylprednisolone improve organ function compared with placebo? * Does methylprednisolone reduce the risk of mortality within 30 days? Researchers will compare high-dose methylprednisolone (160mg/d), low-dose methylprednisolone (80mg/d), and placebo (normal saline) to evaluate effectiveness and safety. Participants will: * Receive high-dose methylprednisolone, low-dose methylprednisolone, or placebo every 12 hours for the first 3 days * Be reassessed on Day 4 based on their inflammatory status If the hyperinflammatory phenotype persists, the treatment dose will be reduced by half and continued until Day 7 or ICU discharge, whichever occurs first If the patient transitions to a hypoinflammatory phenotype, the study treatment will be discontinued * Be monitored daily in the intensive care unit for organ function, inflammatory status, and need for organ support * Be followed for up to 30 days after randomization to assess survival and recovery

Prone position (placing the patient on his abdomen) has been shown to be an effective intervention to decrease mortality in adults connected to mechanical ventilation for moderate to severe Acute Respiratory Distress Syndrome (ARDS). Patients may require one or more sessions of prone position. However, the optimal duration of prone sessions is unknown. The goal of this clinical trial is to learn if applying prone position in prolonged sessions (\> 48 hours - prolonged prone position) is more effective than applying it in daily sessions (16 to 24 hours - intermittent prone position). The trial will also learn about the safety of prolonged prone position compared to intermittent prone position. The main questions it aims to answer are: * Does prolonged prone position increase survival compared to intermittent prone position in participants with moderate to severe ARDS ? * How does prolonged prone position compare to intermittent prone position in terms of medical problems associated to prone position ? Researchers will compare prolonged versus intermittent prone position to see which approach is better to treat moderate to severe ARDS. Participants will: * Receive prone position either in prolonged (\> 48 hours) or daily (16 to 24 hours) sessions during the first 7 days * Be followed for up to 90 days to assess their clinical evolution

Acute respiratory distress syndrome is characterized by heterogeneous lung injury, with dependent regions often collapsed and non-dependent regions relatively well-aerated, forming the so called "baby lung." Mechanical ventilation, while essential, can induce additional lung injury (VILI) via overdistension (baro/volutrauma) or repetitive alveolar collapse (atelectrauma). Protective ventilation strategies with low tidal volumes (VT 6-8 mL/kg predicted body weight, PBW) reduce mortality, but their efficacy relies on accurate PBW estimation, which is derived from patient height. In critical care, height measurement is often challenging, and common methods such as visual estimation or tape measurement can be inaccurate, leading to inappropriate VT settings and increased risk of lung stress and VILI. Alternative methods, including heel-to-knee distance and laser measurement, may offer more precise PBW estimation, yet their impact on lung mechanics in ARDS remains unexplored. This study addresses the knowledge gap by evaluating whether differences in height measurement methods significantly affect lung stress, tidal volume distribution, and ventilatory mechanics in ARDS patients. Patients' heights will be measured using five methods (stadiometer, visual, tape, laser, heel-to knee). Corresponding PBW and tidal volumes (VT = 6 mL/kg PBW) will be calculated and applied in randomized order, each for 30 minutes. Lung stress, ventilatory mechanics, gas exchange, and regional ventilation distribution will be assessed for each VT setting, preceded by a short alveolar recruitment maneuver. During the study, continuous monitoring of hemodynamics and oxygenation will be performed. Ventilatory parameters including plateau pressure, driving pressure, and transpulmonary pressures will be recorded. Electrical impedance tomography will assess regional tidal volume distribution. Each patient's participation is limited to approximately two hours with no further follow-up.

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.

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.

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.

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.

Spontaneous breathing during the transition from controlled to assisted ventilation in ARDS may be harmful, as high respiratory drive can generate large transpulmonary pressure swings and worsen lung injury. Higher PEEP may mitigate this by reducing inspiratory effort and lung stress, but patient response is variable and difficult to predict. While improved lung compliance appears to mediate the protective effects of PEEP, its bedside assessment is complex. Preclinical data suggest that changes in compliance are inversely reflected by changes in respiratory rate, but this relationship and its clinical utility in ARDS patients remain unclear.

The CALMDOWN trial is a prospective, open-label, multicenter, comparative, controlled trial randomizing patients who received near apneic ventilation vs usual care on ECMO (ultra-protective lung ventilation). The study goal is to investigate the benefit of early apneic ventilation in the most severe forms of acute respiratory distress syndrome (ARDS) rescued by ECMO. Indeed, our hypothesis is that that early (near) apneic ventilation on venovenous ECMO for severe ARDS can enhance ventilator injury prevention and therefore reduce ECMO duration and mortality at Day 60.

This study evaluates the safety and potential therapeutic activity of JadiCell™, an investigational umbilical cord-derived mesenchymal stem cell therapy, in patients diagnosed with Acute Respiratory Distress Syndrome (ARDS). JadiCells are administered intravenously and are intended to modulate inflammatory responses and promote tissue repair in injured lung tissue.

Acute respiratory distress syndrome (ARDS) is an inflammatory injury of the lungs caused by various serious illnesses, such as a bacterial or viral lung infection. It is treated by artificial ventilation with the application of positive pressure. Pulmonary injury, coupled with artificial ventilation, can lead to right heart failure which hinders the ejection of blood to the pulmonary circulation. Modern mechanical ventilation modalities have reduced the frequency ("incidence") of this right heart failure in acute respiratory distress syndrome. A large-scale study has shown this a few years ago. However, the evolution of right heart failure during artificial ventilation, and the consequences it has on the patient's cardiovascular status are poorly determined. This study is conducted to improve knowledge in this area. In adult patients hospitalized in intensive care presenting acute respiratory distress syndrome, the investigators will collect the data recorded on cardiac ultrasound, doses of cardiovascular drugs as well as variables reflecting hemodynamic status and cell oxygenation. Data will be collected during the course of ARDS and mechanical ventilation, as well as after weaning from artificial ventilation.

A Phase 2a, randomized, double-blind, placebo-controlled, multiple ascending dose study in patients who are hospitalized with presumed pneumonia requiring supplemental oxygen therapy. The purpose of this study is to examine the safety, tolerability and efficacy of AV-001 Injection administration daily to the earlier of day 28 or EOT (day prior to hospital discharge). A total of 120 eligible patients (20 patients in each of cohort 1, 2 and 3 and 60 patients in cohort 4) will be recruited from up to 25 participating institutions/hospitals. Patients will be randomized in a 1:1 ratio to receive either AV-001 Injection or AV-001 placebo Injection, together with standard of care (SOC).

This study was conducted to determine the effect of Umbilical Cord Mesenchymal Stem Cell (UC-MSC) and Secretome in severe ARDS patients. The study is a randomized control trial - double blind, which has 3 arms intervention namely, Control treatment, UC-MSC treatment, and UC-MSC and Secretome treatment.

To evaluate the safety and efficacy of intravenous (IV) administration of bone marrow mesenchymal stem cell derived extracellular vesicles (EVs), ExoFlo, versus placebo for the treatment of hospitalized patients with moderate-to-severe Acute Respiratory Distress Syndrome (ARDS).

PrismaLung+ is a sterile, single-use medical device aimed at performing partial removal of carbon dioxide (CO2) from the patient's venous blood via diffusion through a membrane. The goal of this prospective, open label, randomized controlled study is to evaluate the efficacy and safety of PrismaLung+ on extracorporeal carbon dioxide removal (ECCO2R) in critically ill patients under invasive mechanical ventilation (IMV). Patients will be randomized to receive either IMV combined with ECCO2R (using PrismaLung+) in the study group or IMV alone in the control group, at a ratio of 2:1.

Primary Objective: To evaluate the safety and tolerability of human umbilical cord mesenchymal stem cell injection in the treatment of moderate/severe acute respiratory distress syndrome.Secondary Objectives: To explore the efficacy and appropriate dosage of human umbilical cord mesenchymal stem cell injection in the treatment of moderate/severe acute respiratory distress syndrome.Exploratory Objective: To explore the immunogenicity and pharmacokinetic/pharmacodynamic (PK/PD) characteristics of a single dose of human umbilical cord mesenchymal stem cell injection in patients with moderate/severe acute respiratory distress syndrome.

The goal of this observational clinical trial is to learn about the role white blood cells (macrophages) play in lung inflammation in people with Acute Respiratory Distress Syndrome (ARDS). The main questions it aims to answer are: 1. How does the immune system respond to different kinds of lung injury and inflammation and how do those processes differ from each other? 2. What roles do the cells that live in the lungs (macrophages) play in turning off inflammation? How does their role differ from other cells that are called to the lung to help repair injury (recruited macrophages)? 3. Will more frequent testing of lung cell samples help reduce the time it takes to start treatment for ventilator-associated pneumonia (VAP) and therefore reduce the rates of initial therapy failure? Participants will be in the intensive care unit (ICU) on a mechanical ventilator (machine that helps patients breathe) because they have ARDS or are on a mechanical ventilator for some other reason (control group). The following will happen: 1. Participants will be given 100% oxygen through the breathing machine (mechanical ventilator) for 3-5 minutes. This is called pre-oxygenation. 2. A lung specialist (pulmonologist), a member of Dr. Janssen's research team, or respiratory therapist will place small amount of saline into the lung using a long catheter going through the breathing tube. 3. The fluid will be removed with suction and will be sent to the laboratory for testing. 4. This will be repeated two more times over the course of 10 days, or less if participants are taken off of the ventilator. The procedure will be performed no more than three times. 5. Two nasal brushings will be taken from the participants' nose. 6. Approximately 3 tablespoons of blood will be removed by putting a needle into the participants vein. This is the standard method used to obtain blood for tests. A total of 9 tablespoons will be taken for research purposes over the course of this study 7. Data including the participants age, sex, severity of illness, and other medical conditions will be recorded to determine how these can affect the white blood cells. 8. If bacteria are isolated from the fluid in the participants lung, the participants' physician may choose to place the participants on antibiotics to treat an infection. 9. A follow-up phone call may be made by a member of the research team after discharge from the hospital. At this time, the participant may be invited to participate in the Post-ICU clinic at National Jewish Health.

Study Title: EIT-Guided Lung Recruitment Maneuvers in Pediatric ARDS: Effects on Ventilation Distribution and Respiratory Mechanics Study Objective: The primary goal of this clinical trial is to determine whether lung recruitment maneuvers guided by Electrical Impedance Tomography (EIT) result in a more homogeneous ventilation distribution and less injurious ventilation in children with pediatric Acute Respiratory Distress Syndrome (pARDS). The study will assess changes in intrapulmonary gas distribution and respiratory mechanics during recruitment maneuvers using both EIT and partitioned respiratory mechanics. This is a prospective cohort study involving children diagnosed with pARDS. Eligible participants will be consecutively enrolled over time and will undergo a standardized series of staircase lung recruitment maneuvers under continuous EIT monitoring. The final mechanical ventilation (MV) settings will be individualized and titrated based on the EIT-derived response to recruitment. Main Research Questions: How can lung recruitment maneuvers be performed safely in children with pARDS? How can we monitor the physiological effects of recruitment on respiratory mechanics? How does recruitment influence the distribution of ventilation within the lungs? Eligible participants will undergo a series of staircase lung recruitment maneuvers under continuous EIT monitoring. The final mechanical ventilation (MV) settings will be titrated and individualized based on the EIT-derived response to recruitment.

In this study, 120 patients with Acute Respiratory Distress Syndrome (ARDS) will be included on a two years-period in an intensive care unit (Assistance Publique des Hôpitaux de Marseille, France). Those patients will benefit from a blood test at inclusion in order to measure several coagulation biomarkers, including EV-TF. Subsequently, these patients will be treated according to the usual practices of the department, following recommendations. Patients who received an injected CT scan between Day 5 and Day 28 will be divided into two groups based on the presence or absence of a pulmonary embolism on imaging. The measured values of EV-TF levels and other studied biomarkers will be compared between these two groups in order to detect a possible association between them and the diagnosis of pulmonary embolism. It should be noted that patients receiving an injected CT-scan between Day 5 and Day 7 will be included in the main analysis while those receiving it between Day 8 and Day 28 will be included in the secondary analysis. Others will be excluded from any analysis. At the same time, several collections of clinical data will be carried out: on Day 1, Day 7, Day 28, and on the day of the CT scan if it is performed at another time.

This study is designed to evaluate the safety and efficacy of fostamatinib in hospitalized adult participants with acute respiratory distress syndrome (ARDS).