33 Clinical Trials for Various Conditions
The study aims to assess the potential benefit and evaluate the safety and tolerability of a single subcutaneous (SC) dose of VIB7734 in hospitalized patients with documented infection of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) with pulmonary involvement. Subjects will be administered a single dose of VIB7734 injected under the skin, assessed for efficacy for 28 days and followed for an additional 42 days.
Healthy biological systems are characterized by a normal range of "variability" in organ function. For example, many studies of heart rate clearly document that loss of the normal level of intrinsic, beat-to-beat variability in heart rate is associated with poor prognosis and early death. Unlike the heart, little is known about patterns of respiratory variability in illness. What is known is that, like the heart, healthy subjects have a specific range of variability in breath- to-breath depth and timing. Additionally, in animal models, ventilator strategies that re-introduce normal variability to the breathing pattern significantly reduce ventilator-associated lung injury. Critically ill patients requiring mechanical ventilation offer an opportunity to observe and analyze respiratory patterns in a completely non-invasive manner. Current mechanical ventilators produce real-time output of respiratory tracings that can analyzed for variability. The investigators propose to non-invasively record these tracings from patients ventilated in the intensive care units for mathematical variability analysis. The purpose of these pilot analyses are to: (1) demonstrate the range of respiratory variability present in the mechanically ve ventilated critically ill and (2) demonstrate the ventilator modality that delivers or permits the closest approximation to previously described beneficial or normal levels of variability. Future studies will use this pilot data in order to determine if the observed patterns of respiratory variability in mechanically ventilated critically ill subjects have prognostic or therapeutic implications.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are similar conditions in which the lungs are critically injured by another inflammatory process in the body. Together they affect more than 150,000 people per year in the United States, with mortality approaching 50% and a financial burden estimated to exceed $5 billion. Fluid overload, weight gain, and reduced oncotic pressure (low blood proteins) are associated with prolonged need for mechanical ventilation and mortality in patients with ALI/ARDS. Historical studies have provided conflicting evidence for benefits with colloid or diuretic therapy in ALI/ARDS, but recent clinical trials have demonstrated significant improvements in blood oxygen levels. The mechanisms of these benefits are not yet certain, but appear to relate to albumin's (a protein medicine) specific ability to influence injury and inflammation in the lungs, thus improving the ability for the lung to repair and exchange oxygen. The purpose of this project is to determine the effects of therapies that affect blood proteins on their ability to change the way the lungs and cardiovascular system (heart and blood vessels) function. Special measurements will be taken to understand how these protein medicines change the ability of the lung and whole body to recover from widespread injury, with additional measures of specific heart and lung function. This clinical trial randomizes ALI/ARDS patients with low blood protein levels to receive albumin (a natural blood protein that is known to influence inflammation) or hetastarch (a synthetic blood protein) with diuretic therapy targeted to improve respiratory function. Therapeutic effects on respiratory function and blood oxygen levels, extravascular lung water, oncotic pressure, lung fluid removal, and heart function will be characterized. This trial will advance our understanding of treatment of ALI/ARDS and the factors that affect fluid balance in the lungs of these patients. Funding Source - FDA Office of Orphan Products Development (OOPD)
The purpose of this study is to determine whether fish oil (containing omega-3 fatty acids) given enterally is safe and effective in reducing lung and systemic inflammation seen in acute lung injury.
This is a Phase 1 pharmacokinetic (PK) study in healthy participants to assess the plasma pharmacokinetics, safety, and tolerability of a single inhaled dose of nezulcitinib (TD-0903) with supplemental oxygenation.
This Phase 2 study will evaluate the efficacy, safety, pharmacodynamics and pharmacokinetics of inhaled TD-0903 compared with a matching placebo in combination with standard of care (SOC) in hospitalized patients with confirmed COVID-19 associated acute lung injury and impaired oxygenation.
Electrical impedance tomography (EIT) monitoring has been researched as a method to determine the spatial impedance distribution in a body cross section, but has yet to become an established clinical tool. EIT monitoring gives a dynamic, breath-to-breath measurement of both global and regional ventilation. Recently, there has been evidence that EIT monitoring has great potential to become a non-invasive bedside tool for assessment of regional lung ventilation without documented hazards. Potential applications include any adult patients in acute respiratory failure. Data collected from this research may contribute to improved patient safety outcomes. PURPOSE: The purpose of this pilot study is to examine the feasibility of using the EIT monitor in intensive care unit (ICU) setting on patients with acute respiratory failure and to compare the EIT monitor data to standard of care patient assessments. It is hypothesized that the EIT monitor, when applied to adults in acute respiratory failure, will correlate with conventional standard of care assessments for these patients.
Lung transplant recipient survival lags other solid organ recipients, with the main early cause of death being primary graft dysfunction (PGD). PGD occurs in up to 1/3 of all recipients, is driven by the body's innate immune response, and has no known medical therapies for treatment or prevention. Investigators have recently shown that Natural Killer (NK) cells, a key innate immune cell, are critical in causing PGD. Importantly, the investigators found that Maraviroc, an FDA-approved drug that works to inhibit these immune cells, prevented lung injury in mouse models of PGD. The goal of this clinical trial is to learn if Maraviroc works to treat PGD in Lung Transplant patients who are above the age of 18 and have a PGD risk score greater than 50%. The objectives the study hopes to address are: To address the safety and tolerability of Maraviroc. To test a strategy for PGD enrichment in a lung transplant population. To measure the efficacy and biological efficacy of using Maraviroc. To study the biochemical, physiologic, and molecular effects of the drug on the body. This will be a double blind study where patients will either get the Maraviroc drug or a placebo. Researchers will then compare the two groups to address the above objectives. Participants will: Take drug Maraviroc or a placebo every 12 hours for 3 days post surgery. Follow up will occur during the entire length of stay at UCSF, about 16 days, with a single 12 month follow up once released.
APRV mode of ventilation will result in an improved partial pressure of arterial oxygenation/ fraction of inspired oxygen (P/F ratio) on day 3 of mechanical ventilation. Sub hypotheses: APRV will be associated with a reduced amount of sedation used during the ICU stay in patients with respiratory failure. APRV will be associated with a reduction in the amount of vasoactive medication used for blood pressure support in patients with respiratory failure.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are devastating disorders associated with lung inflammation, low oxygen levels and respiratory failure in children. Prevalence of ALI ranges from 2.2 to 12 per 100,000 children per year. Using these estimates, up to 9,000 children each year will develop ALI/ARDS, which may cause upto 2,000 deaths per year. Currently, there are no specific therapies directed against ARDS/ALI in children. In adult patients, use of steroids early in the course of ARDS appears promising. There are no published clinical trials examining the use of steroids for the treatment of ALI/ARDS in children. Hypothesis: Subjects with ALI/ARDS receiving steroids early in the course of disease (within 72 hours) and longer than 7 days will have improved clinical outcomes as compared to placebo control group as defined by (a) a decreased duration of mechanical ventilation and (b) significantly increased PaO2/FiO2 ratios.
This study will compare two ventilator modes in mechanically ventilated patients with acute lung injury. Acute lung injury (ALI) is a condition in which the lungs are badly injured and are not able to absorb oxygen the way healthy lungs do. About 25% of patients who are ventilated get ALI. ALI causes 75,000 deaths in the US each year. Ventilators can be set to work in different ways, called modes. One mode, called ARDSNet, pumps a small amount of air into the patient's lungs and then most of the air is released prior to the next breath. Another mode, called Airway pressure release ventilation (APRV), keeps air in the lungs longer between breaths. Both of these modes are currently used at this hospital. The investigators think APRV may help patients with ALI, but we do not know for sure.
Acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) represent a spectrum of clinical syndromes of rapid respiratory system deterioration that are associated with both pulmonary and systemic illness. These syndromes are associated with 30-40% mortality with our current standard of care and are responsible for approximately 75,000 deaths in the US yearly. Current evidence-based care of ALI consists of a strategy of mechanical ventilation utilizing low lung volumes (ARDSNet ventilation) intended to limit further stretch-induced lung injury exacerbated by the ventilator. However, this strategy has been shown to be associated with increased lung injury in a subset of patients and still is associated with about a 30% mortality rate. Airway pressure release ventilation (APRV) is a different, non-experimental strategy of mechanical ventilation currently in routine clinical use. APRV is a pressure-cycled ventilator mode that allows a patient a greater degree of autonomy in controlling his or her breathing pattern than ARDSNet ventilation. Use of APRV has been associated with better oxygenation, less sedative usage, and less ventilator-associated pneumonia in small studies compared with other ventilator modes. However, debate exists over whether APRV might result in decreased or increased ventilator-associated lung injury when compared with ARDSNet ventilation. We intend to implement a randomized, cross over study looking at biomarkers of lung injury in patients with acute lung injury during ventilation with APRV and using the ARDSNet protocol. Our hypothesis is that airway pressure release ventilation is associated with lower levels of lung injury biomarkers than ARDSNet ventilation.
This is an early phase (Phase IIa), randomized, double-blind, parallel group, multi-centre study for subjects with trauma (physical injury) who are at risk for developing Acute Lung Injury (ALI) or Acute Respiratory Distress Syndrome (ARDS). The primary purpose of the study is to evaluate the safety and tolerability of SB-681323, which is a potent, selective inhibitor of p38 alpha (MAPK) (prevents inflammation of tissue), in comparison to a placebo.
Lung units which participate in gas exchange are known as 'recruited' lung. Patients with lung injury suffer from a proportion of units which do not participate in gas exchange (i.e. the derecruited state), which results in impaired gas exchange and induces an inflammatory cascade. Currently, there is no clinical practice guideline in our intensive care unit regarding lung recruitment strategies for children with lung injury. While many studies have demonstrated efficacy (ability to open the lung) and safety of recruitment maneuvers in adults, no such studies have been performed in children. The primary purpose of this study is therefore to demonstrate the safety and efficacy of a recruitment protocol designed to maximally recruit collapsed lung in children with acute lung injury. Each study patient will follow a recruitment protocol (see Appendix 2). Two 'controls' will be utilized in this study: baseline ventilation (no recruitment maneuver) and the open lung approach (a sustained inflation followed by increased PEEP). Efficacy will be defined as an improvement in lung volume (as measured by nitrogen washout and electrical impedance tomography), and by an improvement in measured arterial partial pressure of oxygen. Safety will be defined as the incidence of barotrauma and hemodynamic consequences which occur during the protocol. A secondary purpose of this study will be to further validate electrical impedance tomography (EIT) as a non-invasive tool describing the lung parenchyma by comparing it to an accepted standard method of measuring lung volumes, the multiple breath nitrogen washout technique. Validation of EIT would allow clinicians to have a non-invasive image of a patient's lungs without the risks imposed by radiography. The information we learn will be instrumental in defining an optimal strategy for lung recruitment in children with lung injury.
Acute Lung Injury/Acute respiratory distress syndrome (ALI/ARDS) is a serious and frequently encountered entity in modern ICUs. Sepsis remains the most common cause of ALI/ARDS and carries the worst prognosis. The disease is characterized by an intense inflammatory process. This inflammation plays a major role in the development of gas exchange abnormalities seen in the course of the disease. Statins, primarily used as lipid-lowering agents, are now known to possess anti-inflammatory, antioxidant, antithrombogenic and vascular function-restoring actions. Therefore the investigators propose to determine if Simvastatin may be useful in decreasing the incidence of this deadly syndrome in critically ill patients.
This study will evaluate the safety of a 96-hour intravenous vitamin C infusion protocol (50 mg/kg every 6 hours) in patients with hypoxemia and suspected COVID-19.
The aim of this study will test the safety, tolerability, and efficacy of RLS-0071 for approximately 28 days in comparison to a placebo control in patients with acute lung injury due to COVID-19 pneumonia in early respiratory failure. Patients will be randomized and double-blinded for two parts, a single-ascending dose (SAD) part and a multiple-ascending dose (MAD) part. The name of the study drug involved in this study is: RLS-0071.
Acute lung injury (ALI) and the more severe manifestation, acute respiratory distress syndrome (ARDS) describe syndromes of acute onset, bilateral, inflammatory pulmonary infiltrates and impaired oxygenation. ARDS/ALI are a continuum of disease which results in a life threatening, rapidly progressive illness and occurs in critically ill patients. Recent reports in the Journal of the American Medical Association (JAMA) highlight the significant public health impact ARDS/ALI has on the critically ill population in that despite robust research efforts, these illnesses continue to be under diagnosed, under treated, and continue to have a high mortality rate (≥ 40% of all confirmed diagnoses). The estimates for ARDS/ALI incidence vary due to inconsistencies with proper diagnosis and lack of valid biomarkers of disease; however, it is expected that anywhere from 20-50% of patients on mechanical ventilation will develop this disease. Previous work by our group has shown that sphingolipids play a multifaceted role in lung inflammation. Sphingolipid are a class of bioactive lipids that play a role in cellular processes such as apoptosis, cell migration, and adhesion. Ceramide is one species of sphingolipid the investigators have examined in both man and mouse. Our laboratory has shown that ceramide is up-regulated in pulmonary inflammation in mouse models of pneumonitis and is elevated in the exhaled breath condensate of mechanically ventilated patients at risk for ARDS/ALI. Our work coupled with the work of others highlighting a role for ceramide in chronic obstructive pulmonary disease (COPD), surfactant dysfunction, and infectious disease make ceramide a logical candidate biomarker that warrants further investigation. To our knowledge, there are no studies examining the role of ceramide as a biomarker in ARDS/ALI. Thus, our overarching hypothesis is that ceramide is elevated in the lungs of patients who develop ARDS/ALI. This lipid dysregulation accounts for the pathophysiology seen in this disease and may be a potential pharmacologic target for clinical treatment. Thus the purpose of this exploratory research is to maximize existing specimens to further evaluate ceramide as a biomarker for acute lung injury.
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.
This is a prospective, randomized (1:1), double-blind, multi-center, Phase II clinical study to test the safety and efficacy of a recombinant chimeric anti-tissue factor antibody (ALT-836) versus placebo in patients with sepsis and acute lung injury/acute respiratory distress syndrome (ALI/ARDS). This study was divided into two parts and the first part of the study has been completed. In the first part of the study, sixty patients were randomized at a 1:1 ratio to receive one dose of the study drug or placebo. In the second part of the study, ninety patients will be randomized at a 1:1 ratio to receive a multi-dose treatment regimen of single doses every 72 hours up to a maximum of 4 doses of the study drug or placebo, provided there are no safety concerns.
The purpose of this study is to compare airway pressure release ventilation (APRV) to conventional mechanical ventilation (MV) in patients with acute lung injury (ALI) to determine if APRV can reduce agitation, delirium, and requirements for sedative medications. We will also compare markers of inflammation in the blood and lung to determine if APRV reduces ventilator-induced lung injury (VILI), compared to conventional mechanical ventilation. The proposed study is a randomized, crossover trial. We plan to enroll 40 patients with ALI and randomize to APRV or conventional MV for 24 hours. After this time the patients will be switched to the alternative mode of ventilation (MV or APRV) for another 24 hours. To assess breathing comfort, at the end of each 24-hour period we will measure the amounts of sedative and analgesic medications used. We will also measure the concentrations of markers of inflammation in the blood and lung as measures of VILI. Finally, throughout the study we will compare the adequacy of gas exchange with APRV compared to conventional MV.
Acute lung injury (ALI) is a severe lung condition that causes respiratory failure. The ARDS Network (ARDSNet) is a National Heart, Lung, and Blood Institute-sponsored network that is focused on improving treatments for people with ALI and a similar condition called acute respiratory distress syndrome (ARDS). This study will evaluate participants who were enrolled in one of three ARDSNet studies to examine how the treatments carried out in the prior studies affect participants' long-term health outcomes and quality of life.
This study will test the hypothesis that administration of granulocyte-macrophage colony stimulating factor (GM-CSF) to patients with acute lung injury/acute respiratory distress syndrome (ALI/ARDS) will improve the clinical course and outcome by shortening the duration of mechanical ventilation for these patients.
An assessment of early management of moderate-severe ARDS in the United States, including ventilator management and use of rescue therapy.
The primary hypothesis was that early aspirin administration will decrease the rate of developing acute lung injury during the first 7 days after presentation to the hospital.
Given the possible prognostic relationship between exhaled breath condensate pH and clinical symptoms, it is quite plausible that exhaled breath condensate pH can prove useful in the intensive care unit. For example, if exhaled breath condensate pH falls prior to the onset of clinical symptoms, it is likely that it can be useful as an early marker, heralding the onset of various inflammatory lung diseases. Specifically, exhaled breath condensate pH could be used as a safe, non-invasive screening tool for Ventilator Associated Pneumonia. Similarly, just as changes in exhaled breath condensate pH might predict the onset of disease, exhaled breath condensate pH changes might also mark the progression or resolution of disease (e.g. alerting clinicians to possible readiness for extubation). Although such notions are hypothetical, they are beginning to be supported by anecdotal evidence.
This phase II multi-centered, randomized controlled trial of mechanical ventilation directed by esophageal pressure measurement will test the primary hypothesis that using a strategy of maintaining a minimal but positive transpulmonary pressure (Ptp = airway pressure minus pleural pressure) throughout the ventilatory cycle will lead to an improvement in patient survival.
This was a randomized, double-blind, placebo-controlled Phase 2/3 study to evaluate the safety and efficacy of dociparstat sodium in adult patients with acute lung injury (ALI) due to Coronavirus Disease 2019 (COVID-19). This study was designed to determine if dociparstat sodium could accelerate recovery and prevent progression to mechanical ventilation in patients severely affected by COVID-19.
Brief Summary: SARS-CoV-2 virus infection is known to cause Lung Injury that begins as dyspnea and exercise intolerance, but may rapidly progress to Critical COVID-19 with Respiratory Failure and the need for noninvasive or mechanical ventilation. Mortality rates as high as 80% have been reported among those who require mechanical ventilation, despite best available intensive care. Patients with severe COVID-19 by FDA definition who have not developed respiratory failure be treated with nebulized ZYESAMI™ (aviptadil acetate, a synthetic version of Vasoactive Intestinal Polypeptide (VIP)) 100 μg 3x daily plus Standard of Care vs. placebo + Standard of Care using an FDA 501(k) cleared mesh nebulizer. The primary outcome will be progression in severity of COVID-19 (i.e. critical OR severe progressing to critical) over 28 days. Secondary outcomes will include blood oxygenation as measured by pulse oximetry, dyspnea, exercise tolerance, and levels of TNFα IL-6 and other cytokines.
Respiratory disorders are the leading cause of respiratory failure in children. Thousands of children are admitted to a pediatric intensive care unit each year and placed on mechanical ventilators. Despite over 40 years since the first pediatric-specific ventilator was designed, there has been no specific cardiopulmonary directed therapy that has proven superior. While mechanical ventilation is generally lifesaving, it can be associated with adverse events. There is evidence building to suggest that adopting a lung protective ventilation strategy by the avoidance of lung over-distension and collapse reduces death. Therefore, timely discovery of these two lung conditions is extremely important in order to mitigate the effects associated with positive pressure mechanical ventilation. The investigators research team has extensive research experience with a non-invasive and radiation free medical device called electrical impendence tomography (EIT). EIT is intended to generate regional information of changes in ventilation. Meaning it can detect this collapse and overdistension. This additional source of information could help fine tune the mechanical ventilator. A baseline of understanding of how often this occurs in the patients the investigators serve is required. Therefore the investigators propose an EIT observation study in their pediatric ICU patient population.