Clinical Research Directory

Multimodal Physiologic State Intelligence Study

The OMNIPHYS study will investigate whether multimodal ultrasound and other routinely collected clinical and physiologic data can be combined with artificial intelligence to characterize changes in a person's physiologic state over time. The study will examine cardiac, vascular, pulmonary, and systemic physiologic measurements and develop longitudinal models that describe baseline physiology, physiologic perturbation, compensation, deterioration, treatment response, and recovery. The study is observational and will not assign experimental treatments. The goal is to determine whether changes in multimodal physiologic patterns can be identified and characterized earlier and more reliably than conventional single-time-point assessment.

Rhu-pGSN for Acute Respiratory Distress Syndrome (ARDS)

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.

A Comparative Study of Glucocorticoids Efficacy in Acute Respiratory Distress Syndrome

The aim of the work is to compare the efficacy of equivalent doses of methylprednisolone, dexamethasone and hydrocortisone in patients with ARDS

The ARISE Study - Use of Vertical Positioning

The pilot study will randomize 40 ARDS patients who if proning were required would be randomized to upright bed positioning or to stand of care with bed in the head of bed elevation position

Vascular ARDS Recruitment After Inhaled Nitric Oxide

Acute respiratory distress syndrome (ARDS) is when a person's lungs become inflamed, which can be caused by infection, trauma, surgery, blood transfusion, or burn. ARDS often leads to a situation where the person cannot breathe independently and needs machines' help. Once the lungs are inflamed, the small air sacs responsible for exchanging gases (i.e., ventilation) and the blood flow in the lungs (i.e., perfusion) can be affected. In the past, most research focused on studying ventilation physiology and how to help people breathe with machines. Less was done on perfusion because it requires imaging techniques such as computed tomography with intravenous contrast and radiation. One treatment option for low oxygen levels is inhaled nitric oxide (iNO), a gas that can dilate the lung blood vessels and improve oxygenation; however, it is not always clear whether this treatment will work. Prone position has been used for several years in the care of ARDS patients and has been demonstrated to improve survival in more severe patients. It is not known how iNO and prone positioning interact in determining the distribution of pulmonary perfusion and whether their combine use can benefit ARDS patients. Electrical Impedance Tomography (EIT) is a bedside and accessible imaging technique that is radiation-free and non-invasive and can potentially detect changes in lung perfusion. EIT can perform multiple measurements; it is portable and accessible. This prospective interventional study aims to assess changes in regional blood perfusion in the lungs of patients with ARDS in response to iNO and to prone positioning utilizing EIT. The main questions it aims to answer are: 1. If EIT can measure lung regional perfusion response to an iNO challenge of 20ppm for 15 minutes. 2. If EIT can measure the lung regional perfusion responses to prone position, applied alone and in combination with iNO. 3. If EIT is comparable to dual-energy computed tomography (DECT), the gold-standard method, in the detection of changes in regional lung perfusion due to iNO. 4. If EIT can be an imaging marker to identify ARDS severity Participants will be divided into three cohorts: 1. Sub-Cohort 1 (n=60): Participants will be asked to be monitored by EIT before, during, and after the administration of iNO (20 ppm) for 15 minutes (OFF-ON-OFF) in the supine position 2. Sub-Cohort 2 (N=10): Participants will be asked to be monitored by EIT before and during the administration of iNO (20 ppm) for 15 minutes (OFF-ON) in both the supine and in the prone position. The same subjects will be monitored also with DECT in the supine position and then after 30 minutes in the prone position (without NO administration). 3. Sub-Cohort 3 (N=10): In this subset of Sub-Cohort 1, subjects will be asked to be monitored also with DECT (in addition to EIT) in the supine body position before iNO and after 15 minutes while receiving iNO.

Comparison of Different PEEP Strategies in Moderate-to-Severe ARDS Based on Various Bedside Assessment Tools

Many patients admitted to the intensive care unit (ICU) for a severe lung disease called acute respiratory distress syndrome (ARDS) require mechanical ventilation and positive end-expiratory pressure (PEEP) to improve their oxygenation. Ventilator settings-and particularly the level of PEEP-are critical in the management of these patients. In fact, inappropriate ventilator settings can lead to a worsening of the patients' lung disease or compromise their hemodynamic status. PEEP is a pressure maintained by the ventilator during the patient's exhalation to keep the alveoli open throughout the respiratory cycle. When PEEP is increased, if many alveoli open, this is called alveolar recruitment, which is the expected beneficial effect. However, in some patients, increasing PEEP can cause already-open alveoli to become overdistended without opening new alveoli; this is known as pulmonary overdistension. This phenomenon of overdistension will worsen the patient's pulmonary condition and may also lead to hemodynamic deterioration. To date, numerous techniques have been proposed for determining the optimal PEP level (alveolar recruitment without pulmonary overdistension) in these patients, but none can be recommended as the gold standard. The objective of our study is therefore to compare the various existing methods for determining the optimal PEEP level, in order to determine whether these methods are interchangeable and which would be the best method to use to optimize the care of these patients. To this end, the investigators plan to conduct a prospective, observational, multicenter study in the Intensive Care Units of the Nice University Hospital and the European Hospital of Marseille. Patients on mechanical ventilation for ARDS will be included in the study, and medical and laboratory data from the electronic medical records obtained during the various PEEP measurements to determine the optimal PEEP will be analyzed.

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

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

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

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

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.

Anti-CD14 Treatment With IC14 in Hospitalized ARDS Patients

Hospitalized patients with ARDS will be randomized to intravenous treatment with a monoclonal antibody against CD14, called IC14, or placebo. They will be followed for 28 days. The primary outcome is the day 4 oxygenation index assessed as a continuous measure.

AI-Guided Mechanical Ventilation in Children: A Randomized Controlled Trial

This prospective, randomized controlled trial aims to evaluate whether an AI-driven decision support system can improve clinical outcomes for mechanically ventilated pediatric patients (aged 1 month to 18 years) in the PICU, compared to standard care. The primary question addressed is: Do patients whose ventilator parameter optimization decisions are guided by AI assistance achieve a greater number of ventilator-free days within 28 days compared to those managed with standard care by medical staff? Eligible pediatric patients requiring mechanical ventilation following tracheal intubation will be randomly assigned (1:1) to either the AI-guided intervention group or the standard care control group. In the intervention group, physicians will receive real-time, AI-generated recommendations for ventilator parameters to inform clinical adjustments. In contrast, the control group will be managed according to standard clinical protocols. This study seeks to assess whether AI-driven ventilator optimization can effectively improve clinical outcomes and shorten ventilation duration for pediatric patients in the PICU.

ARDS in Children and ECMO Initiation Strategies Impact on Neurodevelopment (ASCEND)

ASCEND researchers are partnering with families of children who receive extracorporeal membrane oxygenation (ECMO) after a sudden failure of breathing named pediatric acute respiratory distress syndrome (PARDS). ECMO is a life support technology that uses an artificial lung outside of the body to do the lung's work. ASCEND has two objectives. The first objective is to learn more about children's abilities and quality of life among ECMO-supported children in the year after they leave the pediatric intensive care unit. The second objective is to compare short and long-term patient outcomes in two groups of children: one group managed with a mechanical ventilation protocol that reserves the use of extracorporeal membrane oxygenation (ECMO) until protocol failure to another group supported on ECMO per usual care.

Validation and Precision Treatment of Inflammatory Subphenotypes in Acute Respiratory Distress Syndrome: A Multicenter Cohort Study

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.

Trans Thoracic Manipulation of Ventilation/Perfusion: the V/Q System

The purpose of this pilot study is to measure the impact of non-invasive pneumatic manipulation of transthoracic pressure on oxygenation in patients with Acute Respiratory Distress Syndrome (ARDS) due to Coronavirus Disease 2019 (COVID 19) who are on mechanical ventilator support. This will be achieved by a pneumatic Vest placed around the chest wall of consenting patients who meet inclusion criteria. The Vest is essentially a non-invasive segmental device placed upon the anterior and posterior right and left aspects of the chest wall. The researchers have the ability to inflate and deflate the chambers of the Vest to achieve preset pressures as determined by the protocol and observe the patient's physiological response. Participants will have up to four hours of intervention with the study intervention, followed by 1 hour of post-intervention observation.

Precision Ventilation vs Standard Care for Acute Respiratory Distress Syndrome

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.

Cognitive Dysfunctions Associated With Delirium in Critically-ill ARDS Patients

Early cognitive assessment of critically-ill acute respiratory distress syndrome (ARDS) patients with delirium using a multidimensional electrophysiological evaluation battery (mEEG) to identify and characterize the neural correlates of cognitive dysfunctions associated with delirium (vigilance, attention, semantic and lexical processing, self-processing), and to develop a prognostic evaluation of neurocognitive and psychological disorders using an innovative non-behavioral approach.

Pressure Opening With Electrical Impedance Tomography

Acute lung injury and ARDS (acute respiratory distress syndrome) are characterized by lung inhomogeneity, leading to a different distribution of the tidal volume (and pressure) within the lung. The quasi-static PV curve is a useful bedside tool to set mechanical ventilation, but it reflects a global behaviour of the lung. The electrical impedance tomography (EIT) is a non-invasive and radiation-free tool, monitoring dynamic changes in gas distribution. Images from EIT can be divided in several regions of interest, allowing to measure regional changes in compliance. The regional derived-EIT PV curve could provide valuable information on airway closure and AOP (airway opening pressure). Recent studies suggest that AOP measured by the ventilator seems to correspond to the AOP of the lowest injured lung. The investigators will perform one pressure-volume (PV) curve with a low-flow insufflation of 5 L/min starting from 0 cmH2O to a maximal airway pressure corresponding to the plateau pressure. During the low-flow insufflation, both ventilator and EIT-derived PV curves will be recorded. All PV curves will be analysed offline by the investigator to detect complete and regional airway closures, and measure AOPs.

Nosocomial Infections in ECMO Patients

Nosocomial Infections (NI) are a common and dreadful complication for patients suffering from Acute Respiratory Distress Syndrome (ARDS) treated with Extracorporeal Membrane Oxygenation (ECMO). Unfortunately, no study has thoroughly evaluated NI in this fragile patient cohort. Newly developed antibiotics may help manage such infections, but their pharmacokinetics (PK) during ECMO has not been evaluated. Objectives of this prospective observational multicenter pharmacological no-profit study are: 1) describe incidence, microbial etiology, and resistance patterns, and assess risk factors for NIs in a large prospective cohort of ARDS patients undergoing ECMO. 2) provide a PK analysis of ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, and cefiderocol in adult patients undergoing ECMO Incidence, microbial etiology, and antibiotic resistance patterns of confirmed NIs will be prospectively collected and analyzed. In the subgroup of patients treated with ceftazidime/avibactam, meropenem/vaborbactam, ceftolozane/tazobactam, or cefiderocol as per clinical practice, blood and bronchoalveolar concentration of the antibiotic will be measured, and PK modeling carried out.

FCV vs PCV in Moderate to Severe ARDS

The goal of this clinical trial is to compare flow-controlled ventilation (FCV) and pressure-controlled ventilation (PCV) in patients with moderate to severe acute respiratory distress syndrome on the intensive care unit. The main questions it aims to answer are: * Is the mechanical power during flow-controlled ventilation lower than during pressure-controlled ventilation * To gain more understanding about other physiological effects and potential benefits of flow-controlled ventilation in comparison to pressure-controlled ventilation (o.a. the end-expiratory lung volume and homogeneity of ventilation). Participants will be randomized between two ventilation mode sequences, being 90 minutes of FCV followed by 90 minutes of PCV or vice versa.

Cardiovascular Magnetic Resonance Prognosticators in Pediatric Oncology Patients With Sepsis

The overall purpose of this protocol is to identify subacute sepsis-associated cardiac disease in pediatric patients with cancer by CMR and evaluate the CMR findings during their follow-up. This will help inform heart failure management decision making. Evidence of dysfunction or elevated T2 values may inform adjustment of afterload reduction and beta blocker administration, and elevated ECV findings will suggest the need for increased surveillance for diastolic dysfunction. Primary Objectives: (Feasibility Phase) To determine the feasibility of cardiac MRI without anesthesia in the immediate post-sepsis period in children with cancer. CMR scanning will be completed within 10 days of presentation - this will allow us to ensure that possible hemodynamic or respiratory instability and renal dysfunction has resolved prior to transport to the MRI scanner during the most acute phase of illness. (Completion Phase) To estimate the frequency of subacute sepsis-associated cardiac disease, including myocardial inflammation and dysfunction, in the post-acute phase (within 10 days of presentation) of severe sepsis in children with cancer

Safety and Efficacy Study of Inhaled Carbon Monoxide to Treat Acute Respiratory Distress Syndrome (ARDS)

This study will be a multi-center, prospective, randomized, partially double-blind, placebo-controlled Phase II clinical trial of inhaled CO (iCO) for the treatment of ARDS. The trial will be conducted at 7 tertiary care medical centers including Weill Cornell Medicine/NewYork-Presbyterian Hospital, Brigham and Women's Hospital (BWH), Massachusetts General Hospital (MGH), Duke University Hospital, Durham Veterans Administration Medical Center, New York-Presbyterian Brooklyn Methodist Hospital, and Duke Regional Hospital. The purpose of this study is to evaluate the safety, tolerability, and efficacy of inhaled carbon monoxide (iCO) for the treatment of ARDS and to examine the biologic readouts of low dose iCO therapy in patients with ARDS

Comparaison of Two Prone Position Techniques on Occurence of Pressure Sores in ICU

Acute respiratory distress syndrome (ARDS) is a diffuse inflammation of the lungs that occurs in a variety of diseases. According to the Berlin definition, ARDS is characterized by diffuse lung damage in patients with predisposing factors. Understanding the physiology of ARDS has led to improved ventilatory management, which must be protective to ensure adequate oxygenation and CO2 clearance. Prone position (PP) is a technique that can reduce mortality in patients with severe ARDS. PP results in a more homogeneous distribution of pulmonary stress and strain, helping to protect the lung against ventilator-induced lung injury (VILI). It also increases the PaO2/FiO2 (P/F) ratio, improves the pulmonary ventilation-perfusion ratio, decreases PaCO2 and promotes ventilation of the dorsal lung regions. This technique should be offered to all patients with severe ARDS for 16 consecutive hours, to improve survival and weaning success from mechanical ventilation. However, PP has adverse effects. A meta-analysis showed an increased risk of pressure sores, possibly linked to generalized acute inflammation associated with significant cytokine discharge and diffuse lesions of the vascular endothelium. PP also increased the risk of obstruction and displacement of the endotracheal tube. Final positioning in PP, (i.e., the position imposed on the patient for the duration of the PP session) varies from one ICU to another, and is rarely described in scientific articles. There are two main variants: 1. prone , with arms alongside the body 2. prone, swimmer's position The aim of our study is to show that the "swimmer" PP reduces the occurrence of stage 3 or higher pressure sores, compared with the "arms alongside the body" PP (standard care) at Day 28 post inclusion.

Non-invasive Vagal Neurostimulation (nVNS) for Traumatic Brain Injury (TBI)-Induced Acute Respiratory Distress

This is a prospective, randomized, two-arm, controlled 30-day investigational pilot trial using the gammaCore Sapphire S non-invasive vagus nerve stimulation (nVNS) device + standard of care (SOC) in newly-hospitalized patients with mild-to-moderate traumatic brain injury (TBI) to prevent the progression towards immunokine storms, systemic inflammatory response syndrome (SIRS), severe respiratory distress, and requirement for invasive mechanical ventilation, and death, when compared to SOC alone (the control arm).