Active clinical trials for "Acute Lung Injury"

Vojta therapy is a physiotherapy intervention with scientific evidence in respiratory pathologies in children and proven in adults. In this pilot study with an RCT design, its effect in adult patients with respiratory pathology caused by the SARS-CoV-2 virus will be studied. The non-invasive and non-painful technique consists of applying tolerable pressure to specific areas of the patient's body. The objective is to activate, in a reflex way, the ventilatory physiology. It is compared with the conventional respiratory physiotherapy approach.

This is a Phase 2 multicenter randomized (2:1), placebo-controlled trial to evaluate early signs of efficacy of allogeneic, umbilical cord-derived (UC) mesenchymal stromal cells (MSCs) in patients with COVID-19 and Acute Respiratory Distress Syndrome (ARDS). Randomized participants (N=54) will receive 3 daily doses of up to 90-million cells/unit dose (cumulative dose of up to 270 million UC-MSCs) or blinded placebo. The MSC product will be provided as 2.5 million cells/ml suspended in PlasmaLyte A containing 5% Human Albumin. The appearance-matched placebo product contains the same excipients, PlasmaLyte A and 5% Human Albumin, as the UC-MSCs.

Considering the potential of mesenchymal stromal cells (MSCs) in the treatment of lung injuries by COVID-19, this pilot clinical trial evaluates the safety and potential efficacy of the cell therapy, administered intravenously, in patients with pneumonia associated with COVID-19-associated acute respiratory distress syndrome.

PEEP titration is a recommended during invasive mechanical ventilation of ICU patients. However, little is known about the right way to conduct this titration. PEEP titration can be conducted by a stepwise increase in PEEP level, or following an ARM and a consecutive stepwise decrease in PEEP level. Those 2 methods will be explored in intubated ICU patients either with healthy lung or ARDS lungs. Physiological exploration will include end-expiratory lung volume measurements, driving pressure, compliance and electro-impedance tomography at each PEEP level.

In a recent multicenter randomized controlled trial, prolonged administration of low-dose methylprednisolone (1mg/kg/day) initiated in early acute respiratory distress syndrome was associated with earlier resolution of pulmonary and extrapulmonary organ dysfunction and reduction in duration of mechanical ventilation and intensive care unit stay. However, glucocorticoids may induce serious adverse events and these adverse events might compensate the positive effect of prolonged methylprednisolone infusion and discourage physicians from treating acute respiratory distress syndrome patients with glucocorticoids. Early prediction of responsiveness to prolonged methylprednisolone infusion would be help to decide whether to continue or not prolonged methylprednisolone infusion and this could reduce the drug related adverse events. We project to evaluate the predictors of responsiveness to prolonged methylprednisolone infusion in early acute respiratory distress syndrome .

Scientific background. Dysregulated systemic inflammation is a key pathogenetic mechanism for morbidity and mortality in ALI/ARDS, and is associated with tissue insensitivity and/or resistance to inappropriately elevated endogenous glucocorticoids. In one study, prolonged methylprednisolone treatment of ARDS patients resulted in rapid and sustained reduction in circulating and pulmonary levels of pro-inflammatory cytokines, chemokines, and procollagen. Preliminary work. Five randomized trials (N = 518) investigating prolonged glucocorticoid treatment in acute lung injury/ARDS reported a significant physiological improvement and a sizable reduction in duration of mechanical ventilation and ICU length of stay. Insufficient data is available on the effects of low dose prolonged methylprednisolone treatment initiated in early ALI/ARDS on mortality. Hypothesis. We hypothesized that the anti-inflammatory activity associated with prolonged methylprednisolone administration improves pulmonary and extra-pulmonary organ dysfunction in early ALI/ARDS and reduces mortality. Objective. To investigate the effects of prolonged low-dose methylprednisolone infusion on mortality and morbidity in early ALI/ARDS. Study design. Multicenter, prospective randomized, placebo-controlled, double-blind clinical trial. Entry criteria. Patients with ALI/ARDS of less than 72 hours duration. Stratification. Patients are prospectively stratified prior to randomization as (1) intubated versus NPPV treated, and (2) ARDS versus severe ARDS. The purpose of stratification is to distribute equally in both arms intubated versus NPPV treated, and ARDS versus severe ARDS. End-points. The primary end-point of trial is 28 days all cause mortality; the secondary end-points are (a) ventilator-free days at 28 days following study entry, (b) organ failure-free days at 28 days following study entry, and (c) duration of ICU stay.

Recent COVID 19 pandemic has overwhelmed health services all around the world, and humanity has yet to find a cure or a vaccine for the treatment of patients, mainly the severe ones, who pose a therapeutic challenge to healthcare professionals given the paucity of information we have regarding SARS-CoV-2 pathogenesis. Recently, reports mainly from China from patients treated with mesenchymal stem cells have shown promise in accelerating recovery, even in the critically ill and the therapy has sustained an increase in research because of it's powerful immunomodulatory effects, making it and interesting alternative in patients with lung and systemic inflammation. These effects could help treat a lot of patients and improve their outcomes, reason why phase I/II studies are needed to show their safety and experimental efficacy.

Corona virus disease 2019 (COVID-19) has been declared as a Pandemic by the World Health Organization (WHO). According to WHO report on March 31st 2020, globally COVID-19 have infected over 750,000 people and caused over 36,000 deaths with case fatality rate of 4.85%. In Indonesia, COVID-19 have infected 1,414 people and caused 122 deaths with case fatality rate of 8.63%. In severe cases, COVID-19 causes complications, such as acute respiratory distress syndrome (ARDS), sepsis, septic shock, and multi-organ dysfunction syndrome (MODS), where age and comorbid illnesses as a major factor to these complications. Up to this point there are several promising therapies for COVID-19 but is not yet recommended and in need of further research. The use of convalescent plasma has been approved by the US Food and Drug Administration (FDA) through the scheme of emergency investigational new drug (eIND). This method has been used as the treatment in several outbreak or plague cases over the years, such as the flu epidemic in 1918, polio, measles, mumps, SARS (severe acute respiratory syndrome), EVD (Ebola virus disease) and MERS (middle-eastern respiratory syndrome) and this treatment shows better outcome. Several case report on the use of convalescent plasma for COVID-19 patients with ARDS and mechanical ventilation has been reported and shows promising outcome. Nevertheless, larger and multicenter research need to be done to assess and evaluate the effectiveness and safety of convalescent plasma therapy on for COVID-19 patients with ARDS.

This research aims to assess the use of an experimental and non-invasive procedure, Remote Ischemic Conditioning (RIC), as an adjunct therapy in attenuating severe COVID-19 disease. An excessive and counterproductive systemic inflammatory response is thought to be a major cause of severe disease and death in patients with COVID-19. Severe ICU cases frequently have markedly higher levels of inflammatory markers such as CRP, IL-6, IL and TNF-a; which is thought to be correlated with increasing disease severity. The relationship between dysregulated inflammatory processes and disease states such as acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are well understood. ALI is characterized by an acute exaggerated mononuclear/neutrophilic inflammatory response followed by progressive collagen deposition in the lung, and if severe enough, may progress to ARDS requiring ventilation.

The main objective of the study is to assess the feasibility, safety, and tolerability of the administration of HCR040, a drug whose active substance is HC016, allogeneic adipose-derived adult mesenchymal stem cells expanded and pulsed with H2O2, in patients with acute respiratory distress syndrome.