Active clinical trials for "Respiratory Distress Syndrome"

Respiratory involvement of SARS-CoV2 leads to acute respiratory distress syndrome (ARDS) and significant immunosuppression (lymphopenia) exposing patients to long ventilation duration and late mortality linked to the acquisition of nosocomial infections. Lymphopenia characteristic of severe forms of ARDS secondary to SARS-CoV2 infection may be linked to expansion of MDSCs and arginine depletion of lymphocytes. Severe forms of COVID-19 pneumonitis are marked by persistent ARDS with acquisition of nosocomial infections as well as by prolonged lymphocytic dysfunction associated with the emergence of MDSC. It has been found in intensive care patients hypoargininaemia, associated with the persistence of organ dysfunction (evaluated by the SOFA score), the occurrence of nosocomial infections and mortality. Also, it has been demonstrated that in these patients, the enteral administration of ARG was not deleterious and increased the synthesis of ornithine, suggesting a preferential use of ARG by the arginase route, without significant increase in argininaemia nor effect on immune functions. L-citrulline (CIT), an endogenous precursor of ARG, is an interesting alternative to increase the availability of ARG. Recent data demonstrate that the administration of CIT in intensive care is not deleterious and that it very significantly reduces mortality in an animal model of sepsis, corrects hypoargininemia, with convincing data on immunological parameters such as lymphopenia, which is associated with mortality, organ dysfunction and the occurrence of nosocomial infections. The availability of ARG directly impacts the mitochondrial metabolism of T lymphocytes and their function. The hypothesis is therefore that CIT supplementation is more effective than the administration of ARG to correct hypoargininaemia, decrease lymphocyte dysfunction, correct immunosuppression and organ dysfunction in septic patients admitted to intensive care. The main objective is to show that, in patients hospitalized in intensive care for ARDS secondary to COVID-19 pneumonia, the group of patients receiving L-citrulline for 7 days, compared to the group receiving placebo, has a score of organ failure decreased on D7 (evaluated by the SOFA score) or by the last known SOFA score if the patient has died or been resuscitated.

The research team is investigating administering exogenous surfactant in COVID-19 patients with ARDS. The overall goal is to improve the outcome (mortality) of mechanically ventilated COVID-19 patients. Although the investigators anticipate that clinical outcomes may improve in the small group of patients receiving exogenous surfactant therapy in this small, single center study, the primary goal is to first determine feasibility and safety.

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.

***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.

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.

This is a multicenter, single-treatment study. Subjects will consist of adults with COVID-19 associated acute lung injury who are being cared for in a critical care environment.

Randomized, double-blind, parallel, two-arms clinical trial to assess the efficacy and safety of 2 infusions of Wharton-Jelly mesenchymal stromal cells (day 1 and day 3, endovenously at 1E6cells/Kg per dose) in patients with moderate acute respiratory distress syndrome (ARDS) secondary to SARS-CoV-2 infection. Follow-up will be established on days 3, 5, 7, 14, 21, and 28. Long term follow-up will be performed at 3, 6 and 12 months.

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).

This study evaluates a pharmacological intervention to relieve dyspnea in intensive care unit patients. Indeed, opioids can be particularly beneficial since 1) dyspnea and pain share many similarities, 2) the benefit of opioids on dyspnea has been clearly demonstrated in other populations. However, to date, data regarding the impact of morphine on dyspnea in intensive care unit patients admitted for acute respiratory failure are scarce. There may be a reluctance of physicians to prescribe opioids that is not scientifically justified. The study will focus on patient reported outcome (PRO) criteria. The ultimate goal of this pilot study is to design the protocol of a future pragmatic trial.

The purpose of this study is to evaluate the efficacy and safety of ruxolitinib in the treatment of patients with COVID-19 severe pneumonia.