Active clinical trials for "Acute Lung Injury"

Study KIN-1901-2001 is a multi-center, adaptive, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of gimsilumab in subjects with lung injury or acute respiratory distress syndrome (ARDS) secondary to COVID-19.

The purpose of this research study is to learn about the safety and efficacy of human umbilical cord derived Mesenchymal Stem Cells (UC-MSC) for treatment of COVID-19 Patients with Severe Complications of Acute Lung Injury/Acute Respiratory Distress Syndrome (ALI/ARDS).

Whereas the pandemic due do Covid-19 continues to spread, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Severe Acute Respiratory Distress Syndrome in 30% of patients with a 30%-60% mortality rate for those requiring hospitalization in an intensive care unit. The main physio-pathological hallmark is an acute pulmonary inflammation. Currently, there is no treatment. Mesenchymal stem cells (MSC) feature several attractive characteristics: ease of procurement, high proliferation potential, capacity to home to inflammatory sites, anti-inflammatory, anti-fibrotic and immunomodulatory properties. If all MSC share several characteristics regardless of the tissue source, the highest productions of bioactive molecules and the strongest immunomodulatory properties are yielded by those from the Wharton's jelly of the umbilical cord. An additional advantage is that they can be scaled-up to generate banks of cryofrozen and thus readily available products. These cells have already been tested in several clinical trials with an excellent safety record. The objective of this project is to treat intubated-ventilated patients presenting with a SARS-CoV2-related Acute Respiratory Distress Syndrome (ARDS) of less than 96 hours by three intravenous infusions of umbilical cord Wharton's jelly-derived mesenchymal stromal cells (UC-MSC) one every other day (duration of the treatment: one week). The primary endpoint is the PaO2/FiO2 ratio at day 7. The evolution of several inflammatory markers, T regulatory lymphocytes and donor-specific antibodies will also be monitored. The trial will include 40 patients, of whom 20 will be cell-treated while the remaining 20 patients will be injected with a placebo solution in addition to the standard of care. Given the pathophysiology of SARS-CoV2, it is thus sound to hypothesize that the intravenous administration of UC-MSC during the initial phase of ARDS could control inflammation, accelerate its recovery with improved oxygenation, reduced mechanical ventilation and ventilation weaning time and therefore reduced length of stay in intensive care. The feasibility of the project is supported by the expertise of the Meary Cell and Gene Therapy Center, which is approved for the production of Advanced Therapy Medicinal Products and has already successfully prepared the first batches of cells, as well as by the involvement of a cardiac surgery team which will leverage its experience with stem cells for the treatment of heart failure to make it relevant to the Stroma-Cov-2 project.

***At this time, we are only enrolling at Houston Methodist Hospital (HMH)/Baylor College of Medicine (BCM) and are not shipping cells outside of BCM/HMH.*** This is a study for patients who have respiratory infection caused by SARS-CoV-2 that have not gotten better. Because there is no standard treatment for this infection, patients are being asked to volunteer for a gene transfer research study using mesenchymal stem cells (MSCs). Stem cells are cells that do not yet have a specific function in the body. Mesenchymal stem cells (MSCs) are a type of stem cell that can be grown from bone marrow (the spongy tissue inside of bones). Stem cells can develop into other types of more mature (specific) cells, such as blood and muscle cells. The purpose of this study is to see if MSCs versus controls can help to treat respiratory infections caused by SARS-CoV-2.

Acute respiratory distress syndrome (ARDS) is defined using the clinical criteria of bilateral pulmonary opacities on a chest radiograph, arterial hypoxemia (partial pressure of arterial oxygen [PaO2] to fraction of inspired oxygen [FiO2] ratio ≤ 300 mmHg with positive end-expiratory pressure [PEEP] ≥ 5 cmH2O) within one week of a clinical insult or new or worsening respiratory symptoms, and the exclusion of cardiac failure as the primary cause. ARDS is a fatal condition for intensive care unit (ICU) patients with a mortality between 30 and 40%, and a frequently under-recognized challenge for clinicians. Patients with severe symptoms may retain sequelae that have recently been reported in the literature. These sequelae may include chronic respiratory failure, disabling neuro-muscular disorders, and post-traumatic stress disorder identical to that observed in soldiers returning from war. The management of a patient with ARDS requires first of all an optimization of oxygenation, which relies primarily on mechanical ventilation, whether invasive or non-invasive (for less severe patients). Since the ARDS network study published in 2000 in the New England Journal of Medicine, it has been internationally accepted that tidal volumes must be reduced in order to limit the risk of alveolar over-distension and ventilator-induced lung injury (VILI). A tidal volume of approximately 6 mL.kg-1 ideal body weight (IBW) should be applied. Routine neuromuscular blockade of the most severe patients (PaO2/FiO2 < 120 mmHg) is usually the rule, although it is increasingly being questioned. Comprehensive ventilatory management is based on the concepts of baby lung and open lung, introduced respectively by Gattinoni and Lachmann. According to these concepts, it must be considered that the lung volume available for mechanical ventilation is very small compared to the healthy lung for a given patient (baby lung) and that the reduction in tidal volume must be associated with the use of sufficient PEEP and alveolar recruitment maneuvers to keep the lung "open" and limit the formation of atelectasis. In addition to this optimization of mechanical ventilation, it is possible to reduce the impact of mechanical stress on the lung. The prone position, for example, makes it possible to free from certain visceral and mediastinal constraints, to optimize the distribution of ventilation as well as the ventilation to perfusion ratios. Thanks to the technological progress of intensive care beds, it is now possible to verticalize ventilated and sedated patients in complete safety. Verticalization could reduce the constraints imposed to the lungs, by reproducing the more physiological vertical station, and thus modifying the distribution of ventilation. Indeed, in two physiological studies published in 2006 and 2013 in Intensive Care Medicine, 30 to 40% of patients with ARDS appeared to respond to partial body verticalization at 45° and 60° (in a semi-seated or seated position). In addition to improving arterial oxygenation, verticalization appeared to decrease ventilatory stress, related to supine position, and increase alveolar recruitment, with improved lung compliance and end-expiratory lung volume (EELV) over time. Nevertheless, 90° verticalization has never been studied, nor have positions without body flexion (seated or semi-seated). In these studies, only patients with the highest lung compliance appeared to respond. These data support the current hypothesis of subgroups of patients with ARDS with different pathophysiological characteristics (morphological and phenotypic) and therapeutic responses. The investigators hypothesize that verticalization of patients with ARDS improves ventilatory mechanics by reducing the constraints imposed on the lung (transpulmonary pressure), pulmonary aeration, arterial oxygenation and ventilatory parameters. The first objective is to study the influence of the bed position of the patient with early ARDS on the variations in respiratory mechanics represented by the transpulmonary driving pressure (ΔPtp). The second objective is to evaluate changes in ventilatory physiology, tolerance and feasibility of verticalization in patients with early ARDS.

The global pandemic COVID-19 has overwhelmed the medical capacity to accommodate a large surge of patients with acute respiratory distress syndrome (ARDS). In the United States, the number of cases of COVID-19 ARDS is projected to exceed the number of available ventilators. Reports from China and Italy indicate that 22-64% of critically ill COVID-19 patients with ARDS will die. ARDS currently has no evidence-based treatments other than low tidal ventilation to limit mechanical stress on the lung and prone positioning. A new therapeutic approach capable of rapidly treating and attenuating ARDS secondary to COVID-19 is urgently needed. The dominant pathologic feature of viral-induced ARDS is fibrin accumulation in the microvasculature and airspaces. Substantial preclinical work suggests antifibrinolytic therapy attenuates infection provoked ARDS. In 2001, a phase I trial 7 demonstrated the urokinase and streptokinase were effective in patients with terminal ARDS, markedly improving oxygen delivery and reducing an expected mortality in that specific patient cohort from 100% to 70%. A more contemporary approach to thrombolytic therapy is tissue plasminogen activator (tPA) due to its higher efficacy of clot lysis with comparable bleeding risk 8. We therefore propose a phase IIa clinical trial with two intravenous (IV) tPA treatment arms and a control arm to test the efficacy and safety of IV tPA in improving respiratory function and oxygenation, and consequently, successful extubation, duration of mechanical ventilation and survival.

Inhalation of toxic gases and chemical irritants during the fire leads to damage to the respiratory tract or the alveolar tissue, which is known as smoke inhalation injury. Acute Respiratory Distress Syndrome (ARDS) is associated with smoke inhalation injury. These patients usually need physiotherapy in the form of chest mobilization and breathing exercises for up to 4 to 6 weeks after discharge from the burns care centre. The patients during this phase are usually in pain and extremely anxious about these exercises. Virtual reality distraction (VRD) is one such technique that is gaining immense popularity recently, it has more immersive distraction when compared to traditional distraction techniques. This study aims to investigate the effect of a virtual reality distraction (VRD) technique as a pain alleviation tool for reducing pain during physiotherapy in burns patients with acute respiratory distress syndrome (ARDS) in a hospital setting.

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.

Barotrauma (pneumothorax, pneumomediastinum) is a well-described complication of Acute Respiratory Distress Syndrome (ARDS), especially in patients with coronavirus disease 2019 (COVID-19) (16.1% in COVID-19, and about 6% in non-COVID-19 ARDS). Macklin effect was recently discovered by our group as an accurate radiological predictor of barotrauma in COVID-19 ARDS; the Investigators also found that density histograms automatically extracted from chest CT images provide a reliable insight into lung composition . Since lung frailty is a major issue also in non-COVID-19 ARDS, the Investigators want to confirm the predictive role of Macklin effect also in this setting. In addition, the Investigators aim to explore inflammatory profiling to decipher different biological aspects of the same clinical issue. Finally, the Investigators want to develop a specific management algorithm for patients diagnosed, according to our findings, with a specific ARDS sub phenotype characterized by increased lung frailty

This Phase I/IIa, multi-center, randomized, placebo-controlled, single-blinded dose-escalation study evaluated TNX-832 (also referred to as ALT-836 and Sunol cH36) in subjects with suspected or proven bacteria-induced ALI/ARDS. Up to five cohorts of at least six subjects each were originally planned. Subjects were to be randomized in a 5:1 ratio to receive TNX-832 or placebo,respectively, administered as a single bolus infusion over 15 minutes. Three cohorts of subjects were enrolled to the study and safety and pharmacokinetics of the study treatment were evaluated.