Clinical Research Directory

Corticosteroids in Hyperinflammatory Phenotype of Critical Illness

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

Nogapendekin Alfa-Inbakicept and iNKT Cells for Critically Ill Adults With Severe Community-Acquired Pneumonia (With or Without Sepsis/ARDS)

This Phase 2 study tests whether adding two immune therapies - nogapendekin alfa-inbakicept (NAI) and off-the-shelf iNKT cell infusions - to standard care can safely help critically ill adults with severe community-acquired pneumonia (CAP) (with or without sepsis/ARDS) recover. The study will give NAI by subcutaneous injection (Days 1 and 10) and one IV dose of iNKT cells (Day 3), then follow participants for 90 days.

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 B: Paridiprubart

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

JUST BREATHE, Breathing Life Into Innovative Therapies for ARDS- Cohort 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.

To Evaluate 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).

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.

Influence of NEP Inhibition on Vascular Leak and Inflammation (NEPi-INFLAMMATION)

Acute Respiratory Distress Syndrome (ARDS) is a severe type of lung injury that affects 10% of patients admitted to Intensive Care Units worldwide, with an unacceptably high mortality of up to 48% in those with the most severe form of the condition. It is a complex and poorly understood syndrome that results in progressive failure of the lungs. Crucially, the inflamed lungs allow fluid to leak from the circulation into the airspace, so that patients' lungs fill with fluid - "drowning from the inside". As this condition progresses, the patient typically requires increasing amounts of oxygen and eventually, support from a ventilator. To date, there are no effective treatments for ARDS that can limit, stop or repair this process. This research study is aiming to look at a naturally occurring substance produced by blood vessels, C-type natriuretic peptide (CNP). The investigators have evidence suggesting that CNP plays a role in maintaining the barrier provided by blood vessels that stops fluid leaking out into tissues. This is based on various studies done on CNP by the investigators research group that have established its widespread role in maintaining cells that line blood vessels and play a vital role in lungs' barrier function: the endothelium. CNP is broken down in part by an enzyme called Neutral endopeptidase and therefore, drugs that inhibit this enzyme would result in increased CNP concentration and activity. If CNP does in fact strengthen the lungs' endothelial barrier, then this class of drug may benefit patients with ARDS. The aim of this experimental medicine study is to assess the effect of using the licensed NEP inhibitor Racecadotril, in a well-established, safe model of inflammation-induced skin blisters in healthy human volunteers to determine primarily whether the fluid accumulation i.e. leak, in these blisters is reduced by treatment with this drug.

Incidence and Evolution of Heart-lung Interaction in Acute Respiratory Distress Syndrome

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.

Mesenchymal Stem Cells (MSCs) and Conditioned Medium Mesenchymal Stem Cells as Adjuvant Therapy for Sepsis

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.

Phase 2a Multiple Ascending Dose Study in Hospitalized Patients With Pneumonia.

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).

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).

A Study of the Efficacy and Safety of Extracorporeal Carbon Dioxide Removal Using PrismaLung+

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.

A Clinical Trial of Human Umbilical Cord Mesenchymal Stem Cell Injection for the Treatment of Severe Acute Respiratory Distress Syndrome

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.

EIT- Guided Lung Recruitment in pARDS

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.

Macrophage Programing in Acute Lung Injury: MiniBAL

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.

Association Between the Level of EV-TF and the Occurence of Pulmonary Embolism in Patients With ARDS

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.

Correlation Between EIT-based Pulse Wave Method for Pulmonary Perfusion Monitoring and Pulmonary Artery Catheter-based Stroke Volume Measurement

The goal of this clinical study is to learn if a new, non-invasive monitoring method called EIT Pulse Wave can accurately measure blood flow to the lungs (pulmonary perfusion) and predict heart stroke volume (SV) in critically ill patients. It will also learn about the safety of this monitoring approach. The main questions it aims to answer are: How well does the EIT Pulse Wave measurement of lung blood flow correlate with the SV measured by the standard method (Swan-Ganz catheter)? Can we build a reliable model to predict SV non-invasively using the EIT Pulse Wave signal? Researchers will compare the EIT Pulse Wave measurements directly with the Swan-Ganz catheter measurements to see if the new method is accurate. Participants will: Be critically ill adults in the ICU who are already receiving mechanical ventilation and have a Swan-Ganz catheter in place for medical reasons. Undergo simultaneous monitoring using both the EIT device and the Swan-Ganz catheter every 30 minutes for up to 48 hours. Have their ventilator settings adjusted to different levels as part of the study protocol while both measurements are recorded.

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).

Pulmonary Fibrosis During Severe COVID-19 Pneumonia

The COVID-19 pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), an emerging coronavirus, which has already infected 192 million people with a case fatality rate close to 2%. About 5% of patients infected with SARS CoV-2 have a critical form with organ failure. Among critical patients admitted to intensive care, about 70% of them will require ventilatory assistance by invasive mechanical ventilation (MV) with a mortality rate of 35% and a median MV duration of 12 days. The most severe lung damage resulting from SARS CoV-2 infection is the acute respiratory distress syndrome (ARDS). The virus infects alveolar epithelial cells and capillary endothelial cells leading to an activation of endothelium, hypercoagulability and thrombosis of pulmonary capillaries. This results in abnormal ventilation / perfusion ratios and profound hypoxemia. To date, the therapeutic management of severe SARS CoV-2 pneumonia lay on the early use of corticosteroids and Interleukin-6 (IL-6) receptor antagonist, which both reduce the need of MV and mortality. The risk factors of death in Intensive Care Unit (ICU) are: advanced age, severe obesity, coronary heart disease, active cancer, severe hypoxemia, and hepatic and renal failure on admission. Among MV patients, the death rate is doubled in those with both reduced thoracopulmonary compliance and elevated D-dimer levels. Patients with severe alveolar damage are at risk of progressing towards irreversible pulmonary fibrosis, the incidence of which still remain unknown. The diagnosis of pulmonary fibrosis is based on histology but there are some non-invasive alternative methods (serum or bronchoalveolar biomarkers, chest CT scan). We aim to assess the incidence of pulmonary fibrosis in patients with severe SARS CoV-2 related pneumonia. We will investigate the prognostic impact of fibrosis on mortality and the number of days alive free from MV at Day 90. Finally, we aim to identify risk factors of fibrosis.

EIT Assessment of Overdistension in ARDS Patients in Prone Position

Mechanical ventilation in ARDS requires protective ventilation with low VT and PEEP. PEEP titration can improve lung recruitment in the dependent lung but with a risk of overdistension in the non-dependant lung. EIT can measure the distribution of tidal ventilation and assess overdistension and collapse during a PEEP titration in any position (prone or not). This study aims to measure the best PEEP as a compromise between recruitment and overdistension during a PEEP trial with EIT before and just after PP.

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.

Safety Study of Inhaled Carbon Monoxide to Treat Pneumonia and Sepsis-Induced Acute Respiratory Distress Syndrome (ARDS)

This study is a multi-center, randomized, partially double-blind, and placebo-controlled Phase Ib clinical trial of inhaled CO (iCO) for the treatment of sepsis-induced acute respiratory distress syndrome (ARDS). The purpose of this study is to evaluate the safety and accuracy of a Coburn-Forster-Kane (CFK) equation-based personalized iCO dosing algorithm to achieve a target carboxyhemoglobin (COHb) level of 6-8% in patients with sepsis-induced ARDS. We will also examine the biologic readouts of low dose iCO therapy in patients with sepsis-induced ARDS.

Recovery From ICUAW Following Severe Respiratory and Cardiac Failure

To observe and identify determinants of recovery from intensive care unit-acquired weakness (ICUAW) following a severe cardiorespiratory failure requiring extra-corporeal membrane oxygenation (ECMO). Additionally, to discover the effects of ICUAW on physical function and health-related quality of life (HRQoL) after critical illness. CLEVERER is a clinical observational pilot study.