Clinical Research Directory

Influence of Personalized Lung Volume Optimization Maneuver on Lung Function and Cardiac Performance in Children

The goal of this randomized interventional clinical trial is to learn if a standardized lung volume optimization maneuver (LVOM) is beneficial in 1. study) children undergoing biventricular repair of their congenital heart disease (CHD) with cardiopulmonary bypass and 2. study) in children with severe respiratory failure at risk for or need for ECMO. The main questions it aims to answer are: Main hypotheses of CHD study: Does a standardized PEEP-Titration maneuver, to optimize end-expiratory lung volume improve: * cardiac performance * lung function Does it make a difference in: * length of ventilation * ventilation/perfusion mismatch of the lung * need for vasopressor support? Main hypotheses of ECMO study: Does a LVOM in children/infants with severe respiratory failure /ARDS * improve lung compliance and gas exchange * facilitate lung protective ventilation according to PALICC-2 guidelines * improve lung aeration and V/Q-matching assessed with EIT Does it make a difference in * need for ECMO * duration of ECMO runs * hemodynamics stability

Respiratory Knowledge Portal Computer and Phone Application to Improve Quality of Mechanical Ventilation by Reducing the Number of Ventilator Associated Events, Injury Created by the Ventilator and Unsafe Setting of Alarms.

Ventilator associated events (VAE) is a quality metric defined by 48 hours of stability followed by 48 hours of escalation of ventilator settings within the ICU. VAE have been associated with poor outcomes and increases the cost of care, yet is not easy to avoid. Operationalizing all the standards of care known to improve outcomes of those requiring mechanical ventilation in the critical care environment requires a comprehensive approach. ICU teams are encouraged to follow best practice protocols to help liberate and prevent VAEs. Yet, compliance with protocols in most ICUs is suboptimal for multiple reasons. With the advent of computerized mechanical ventilators capable of streaming data from breath to breath and biomedical integration systems (BMDI) such as Capsule (UTMB's BMDI system), software systems have been developed to help identify variances in the standard of care. Automation in near real-time ventilator data feedback has been shown to reduce the incidences of VAEs. This quality improvement project will leverage Vyaire's Respiratory Knowledge Portal (RKP) to collect and store meaningful data regarding ventilator-associated events (VAE), alarm policy compliance, ventilator weaning, and lung protective analytics. Goals: 1. To collect quality metrics utilizing RKP from patients requiring mechanical ventilation over a 3-4-month period for a retrospective baseline analysis. 2. Provide the RKP tool to the ICU team to determine if the use of RKP's webportal and Messenger Zebra phone app improves quality of mechanical ventilation and outcomes. 3. To determine a return on investment (ROI) for a software system like RKP.

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 (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 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- 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.

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.

Pilot Study on HA380 Column Use in Critically Ill Patients Receiving Extracorporeal Support.

Patients who are very ill either due to a severe infection, major organ injury, trauma or a major operation may require significant support with devices such as a dialysis machine for the kidneys or Extracorporeal Membrane Oxygenation (ECMO) for the heart and lungs. This is often due to a reaction of the body to the insult which is termed inflammation. The investigators would like to assess if the use of a device that can remove the agents driving this reaction can lead to a quicker recovery form the illness. The device is a blood filter called HA380 and it would be connected to either the dialysis machine or the ECMO circuit. The investigators want to assess the feasibility of conducting a study with the HA380 column. We will also evaluate if the use of the HA380 column has an effect on the time spent on dialysis or ECMO, time spent on the breathing machine, time spent requiring drugs to support blood pressure and time spent in the intensive care unit.

Extracellular Vesicle Treatment for Acute Respiratory Distress Syndrome (ARDS) (EXTINGUISH ARDS)

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).

The APS Phenotyping Study

The goal of the observational APS phenotyping study is to better understand risk factors, potential biomarkers, length and severity of illness, and recovery for adults with ARDS, pneumonia, and/ or sepsis. This study will also generate a biobank of specimens collected from these patients that will be available to investigators for future studies of ARDS, sepsis, and/or pneumonia.

HemodynamIc eFfects of Lung Collapse and overdIstension During ARDS

The management ARDS relies on ventilatory strategies aimed at limiting ventilator-induced lung injury (VILI). The setting of PEEP is still subject of debate, as randomized clinical trials comparing standardized higher versus lower PEEP strategies failed to demonstrate a clear survival advantage. Only few studies explored the hemodynamic effects of various PEEP levels depending on lung recruitability. Furthermore, the role of PEEP-mediated lung collapse and overdistention on patients' hemodynamics has yet to be elucidated. In this physiologic study, the association between EIT-measured lung collapse and overdistention and cardiac function will be explored, accounting for the individual potential for lung recruitment, partitioned respiratory mechanics and cardiac preload responsiveness. Three PEEP levels will be tested in a randomized, crossover fashion: PEEP corresponding to the crossing point between lung collapse and overdistention, PEEP associated with low lung collapse, PEEP associated with low lung overdistention.

Fostamatinib for Treating Acute Respiratory Distress Syndrome (ARDS) in Hospitalized Adults

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

Electrical Impedance Tomography-Based Dynamic Ventilation-Perfusion Functional Phenotype Trajectory in Acute Respiratory Distress Syndrome: A Prospective Observational Study

Acute Respiratory Distress Syndrome (ARDS) is characterized by severe hypoxemia and extensive lung injury. Recent studies indicate that lung functional phenotypes - particularly the distribution and evolution of lung perfusion - may be closely related to patient outcomes. Electrical impedance tomography (EIT) offers non-invasive, bedside, real-time monitoring of lung perfusion patterns and enables classification into distinct phenotypes and trajectory types over the course of illness. To date, limited data exist on perfusion phenotype trajectories in ARDS patients and their relationship with clinical outcomes. This study seeks to characterize dynamic lung dynamic ventilation-perfusion functional Phenotype using EIT and explore their prognostic significance. Objectives Primary Objective: To identify lung perfusion phenotype trajectories in ARDS patients using EIT and assess their association with 28-day mortality. Secondary Objectives: * To determine the relationship between different trajectory types and improvements in oxygenation and respiratory mechanics. * To investigate how ventilator settings (PEEP, driving pressure) interact with perfusion changes. * To support individualized mechanical ventilation strategies based on Ventilation-Perfusion Functional Phenotype monitoring

Enteral Nutrition Delivery in Prone Position Ventilated Patients With Moderate to Severe ARDS

This pilot study is aimed to compare and assess the impact, safety, and practical utility of gastric versus postpyloric feeding in moderate to severe ARDS patients with prone position ventilation. Patients included will be randomly assigned to receive enteral nutrition either through a nasogastric tube or a nasojejunal tube. The primary endpoint is the achievement of enteral nutrition goals. Secondary endpoints include the incidence of hospital-acquired infections, the number of ventilator-free days within 28 days, ICU length of stay, ICU mortality, 28-day mortality, 60-day mortality rates, the incidence of enteral nutrition intolerance, and the rate of enteral nutrition intake.

Impact of Immune Status on Secondary Infections in Patients With Acute Respiratory Failure

This is a retrospective observational study over the period 1/2019 - 02/2024 with the aim of identifying patients with a predisposition to secondary infections.

Careful Ventilation in Acute Respiratory Distress Syndrome (COVID-19 and Non-COVID-19)

This is a multicenter randomized controlled clinical trial with an adaptive design assessing the efficacy of setting the ventilator based on measurements of respiratory mechanics (recruitability and effort) to reduce Day 60 mortality in patients with acute respiratory distress syndrome (ARDS). The CAVIARDS study is also a basket trial; a basket trial design examines a single intervention in multiple disease populations. CAVIARDS consists of an identical 2-arm mechanical ventilation protocol implemented in two different study populations (COVID-19 and non-COVID-19 patients). As per a typical basket trial design, the operational structure of both the COVID-19 substudy (CAVIARDS-19) and non-COVID-19 substudy (CAVIARDS-all) is shared (recruitment, procedures, data collection, analysis, management, etc.).

High PEEP in Noninvasive Ventilation Patients With Pneumonia or ARDS

Noninvasive ventilation is commonly employed in patients with pneumonia or acute respiratory distress syndrome (ARDS) and has been shown to reduce the need for intubation and invasive mechanical ventilation. However, the rate of noninvasive ventilation failure remains substantial, at approximately 40%. Compared with patients in whom noninvasive ventilation succeeds, those who experience noninvasive ventilation failure have a higher likelihood of mortality during their intensive care unit or hospital stay. Therefore, improving the success rate of noninvasive ventilation is clinically important. In patients with lung consolidation receiving invasive mechanical ventilation, high positive end-expiratory pressure (PEEP) can improve oxygenation. Noninvasive ventilation operates on similar physiological principles and can also deliver high PEEP via a mask interface. Nevertheless, there is limited evidence regarding the use of high PEEP during mask-delivered noninvasive ventilation. This study aimed to evaluate whether high PEEP can increase intubation-free survival in patients with pneumonia or ARDS who are treated with noninvasive ventilation.

Retrospective Cohort Study of Low-Flow Extracorporeal Carbon Dioxide Removal (ECCO2R) System: Evaluating ECCO2R's Efficacy and Safety in Participants With Respiratory Failure

This is an observational study performed by retrospective review of data routinely collected for patients receiving low-flow extracorporeal carbon dioxide removal (ECCO2R) therapy in intensive care units (ICUs). Our aim is to firstly, describe the local practice in terms of patient selection and technical details of clinical management related to the use of low-flow ECCO2R system, and secondly, the clinical results in terms of patient outcomes and adverse events. These findings may allow clinicians to improve the quality and safety of ECCO2R therapy provision in the ICU.

Impact of PEEP Trials on Ventilation-Perfusion Matching in ARDS Patients

In the treatment of critically ill patients, mechanical ventilation is a key link, and appropriate mechanical ventilation strategies can open the alveoli and improve oxygenation, while inappropriate mechanical ventilation can increase lung injury and seriously affect the prognosis. Ventilator-related lung injury is mainly concentrated in barotrauma, volumetric injury, shear injury, and biological injury, and the monitoring of respiratory ventilation to the level of local ventilation can help to better assess the state of alveolar opening and alveolar collapse, and help to understand the uniformity of gas distribution in the lungs, which is closely related to lung injury. However, how to achieve simple, bedside and real-time lung ventilation and lung volume assessment in clinical work has always been a difficult problem to be overcome. This study intends to explore the changes of local ventilation and blood flow in the lungs during PEEP trail in patients with ARDS monitored by EIT.

V/Q Matching Variations With PEEP in ARDS According to Compliance-based Phenotypes (France)

This study aim to compare the effect of Positive End Expiratory Pressure (PEEP) on ventilation/perfusion mismatch in two phenotypes of patients with moderate-to-severe Acute Respiratory Distress Syndrome (ARDS), characterized by their respiratory system elastance (Ers). Ventilation/perfusion mismatch will be assessed by Electrical Impedance Tomography (EIT).

Early Severe Illness TrAnslational BioLogy InformaticS in Humans

Advanced stages of the response to life-threatening infection, severe trauma, or other physiological insults often lead to exhaustion of the homeostatic mechanisms that sustain normal blood pressure and oxygenation. These syndromic presentations often meet the diagnostic criteria of sepsis and/or the acute respiratory distress syndrome (ARDS), the two most common syndromes encountered in the intensive care unit (ICU). Although critical illness syndromes, such as sepsis and ARDS, have separate clinical definitions, they often overlap clinically and share several common injury mechanisms. Moreover, there are no specific therapies for critically ill patients, and as a consequence, approximately 1 in 4 patients admitted to the ICU will not survive. The purpose of this observational study is to identify early patient biologic factors that are present at the time of ICU admission that will help diagnose critical illness syndromes earlier, identify who could benefit most from specific therapies, and enable the discovery of new treatments for syndromes such as sepsis and ARDS.

Evaluating AVM0703 for Treatment of COVID-19 or Influenza-mediated ARDS

This is a randomized, double-blinded, placebo-controlled study of AVM0703 administered as a single intravenous (IV) infusion to patients with moderate or severe immediately life-threatening Acute Respiratory Distress Syndrome (ARDS) due to COVID-19 or influenza (A or B). The study is designed to evaluate the safety, tolerability, and pharmacokinetics of single dose of AVM0703 in these ARDS patients.

Hemodynamic Monitoring and Fluid Responsiveness in Venovenous Extracorporeal Membrane Oxygenation (VV ECMO) - "HemodynamECMOnitoring-VV Study"

In extracorporeal membrane oxygenation (ECMO), blood is drawn out of the body via tubes, oxygenated in an artificial lung; and then pumped back into the blood vessels. This allows the supply of oxygen-rich blood to the organs (brain, heart, lungs, kidneys, liver, intestines, etc.) to be maintained. Continuous monitoring of cardiac function and circulatory status (blood pressure, blood flow to organs) is very important in intensive care medicine in order to control the administration of circulation-supporting medication and infusions. Various devices are routinely used for this task. However, in the specific situation of ECMO treatment, the measurements of these devices could be affected due to the artificial circulation; outside the body. The purpose of this study is therefore to test the accuracy of different methods of circulation monitoring during ECMO treatment.

Hemodynamic Monitoring and Fluid Responsiveness in Venoarterial Extracorporeal Membrane Oxygenation (VA ECMO) - "HemodynamECMOnitoring-VA Study"

In extracorporeal membrane oxygenation (ECMO), blood is drawn out of the body via tubes, oxygenated in an artificial lung; and then pumped back into the blood vessels. This allows the supply of oxygen-rich blood to the organs (brain, heart, lungs, kidneys, liver, intestines, etc.) to be maintained. Continuous monitoring of cardiac function and circulatory status (blood pressure, blood flow to organs) is very important in intensive care medicine in order to control the administration of circulation-supporting medication and infusions. Various devices are routinely used for this task. However, in the specific situation of ECMO treatment, the measurements of these devices could be affected due to the artificial circulation; outside the body. The purpose of this study is therefore to test the accuracy of different methods of circulation monitoring during ECMO treatment.