There are 93 clinical trials

Clinical Trials

1 Clinical Evaluation and Management of Persons With Severe Acute Respiratory Syndrome (SARS)

This study will evaluate and treat people with SARS, a new type of pneumonia (lung infection) originating in China. SARS is caused by a new virus that is easily transmitted from person to person. This study will look at the course of the disease; determine how the virus affects the body and how the body fights the infection; and evaluate diagnostic tests to quickly identify the disease. People 18 years of age and older with probable or suspected SARS may be eligible for this study. Close contacts of patients with SARS, patients who recovered from SARS, and NIH health care workers involved in the care of patients will also be enrolled. Patients with SARS who require hospitalization will be admitted to the NIH Clinical Center. Because SARS spreads easily, hospitalized patients will be in a room by themselves and will not be allowed any visitors. They will not leave their room except for tests, such as x-rays. All participants will have a full medical examination, including a medical history, physical examination, and blood tests. In addition, the participants undergo various tests and procedures as follows: - Probable and suspected SARS patients may be hospitalized or may be seen as outpatients. They are provided the treatment judged best for their disease, usually according to expressed or published recommendations. The best treatment for SARS is not yet known, and there have been no studies evaluating therapies. Outpatients are seen three times a week for 2 weeks, once a week for 4 more weeks, and then at 6 months. Patients have mouth and throat swabs taken three times a week for the first 2 weeks, then once a week for 4 more weeks. Blood is drawn three times a week for the first 2 weeks, then once at weeks 3, 4, and 6. If virus is still detectable after 6 weeks, nose washings and throat swabs are repeated until no virus is detected for 3 weeks in a row. In addition, patients provide urine and stool samples, have a chest x-ray and electrocardiogram, and undergo bronchoscopy and bronchial lavage. For the bronchoscopy, a bronchoscope (pencil-thin flexible tube) is passed into the large airways of the lung, allowing the physician to examine the airways. Cells and secretions from the airways are rinsed from the lung with salt water. A brush the size of a pencil tip is passed through the bronchoscope to scrape cells lining the airways and pieces of tissue are collected for analysis. - Close contacts of patients are evaluated twice a week for 2 weeks, then once a week for 2 more weeks. Blood is drawn at the first visit and then at 1, 2, and 4 weeks. Mouth and throat swabs, nose washings, and sputum collections are done twice a week for 2 weeks, then once a week for 2 more weeks. Urine and stool samples are collected once a week for 4 weeks. If virus from the nose or throat is still detectable after 4 weeks, weekly nose washings and throat swabs continue until no virus is detected for 3 weeks in a row. Blood may also be drawn during the weekly visits. - Recovered SARS patients provide blood, urine, and stool samples and have a mouth and throat swab and nose aspiration to see if the SARS virus is present. For the nasal aspiration, salt water is put in the nose and then suctioned out. Usually, these tests are done only once. If virus is detected, however, the nose washing, throat swabs and blood tests are repeated once a week until no virus is detected for 3 weeks in a row. - Health care workers document their contact with patients, use of isolation procedures and equipment, and any unexpected events that occur during contact. They are evaluated for symptoms of infection and provide a blood sample once a month

NCT00073086 Severe Acute Respiratory Syndrome

MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Syndrome

2 The Interaction Between Severe Acute Respiratory Distress Syndrome Viral Proteins and Monocytes

Severe acute respiratory syndrome (SARS) is a new threat to public health since November, 2002. The SARS is highly contagious and is believed to be transmitted by person-to-person through droplet and direct contact. The patients present with fever, chills, cough, myalgia, dyspnea, and diarrhea. The symptoms aggravate in the second week and nearly 40% of the patients develop respiratory failure that requires assisted ventilation. The mortality rate is reported as 6.5%-7%. After several months, the world scientists found the etiology to be a new coronavirus not belonging to the previous coronavirus group I, II and III. The new virus is called SARS associated coronavirus (SARS-CoV). Although the high morbidity and mortality of SARS occurred in adults, there was rare mortality reported in the children. The report from Hong Kong pointed out that the symptoms of SARS in younger children were milder and the clinical course was not as aggressive as in adults. Therefore, the aim of the project is to design the experiment to see the differences of immunological responses to SARS-CoV protein in healthy younger children, teenagers, and adults. The investigators hope that the result could explain the reason for milder disease in younger children and the immunological pathogenesis of SARS.

NCT00172263 Severe Acute Respiratory Syndrome Procedure: blood sampling

MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Syndrome

3 A Multi-centre, Double-blinded, Randomized, Placebo-controlled Trial on the Efficacy and Safety of Lopinavir / Ritonavir Plus Ribavirin in the Treatment of Severe Acute Respiratory Syndrome

The study aims to examine whether the combination of Lopinavir/Ritonavir plus Ribavirin for treatment of severe acute respiratory syndrome (SARS) is superior to placebo.

NCT00578825 Severe Acute Respiratory Syndrome Drug: Lopinavir / Ritonavir plus Ribavirin

MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Syndrome

4 An International Observational Study to Characterize Adults Who Are Hospitalized With Influenza or Other Targeted Respiratory Viruses

Following the sudden and unexpected emergence of influenza A(H1N1)pdm09 (2009 H1N1) virus, this observational study was initiated to estimate rates of morbidity and mortality and to examine predictors of severity among participants with 2009 H1N1 infection. In 2011, as surveillance indicated that 2009 H1N1 virus was co-circulating with other seasonal influenza A and B viruses worldwide, the protocol was expanded to include other influenza A subtypes and influenza B viruses. The current version of the protocol (released in August 2013) further broadens the scope of this observational study. With the recognition that novel respiratory viruses other than novel influenza A viruses, e.g., Middle East Respiratory Syndrome Coronavirus (MERS-CoV), could become prevalent and of major public health importance, the objectives of this protocol have been expanded.

NCT01056185 Influenza Novel Respiratory Virus-1 Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) Novel Respiratory Virus-2 Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)

MeSH:Influenza, Human Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome Virus Diseases

5 A Prospective, Multi-center Registry for Patients With Short Bowel Syndrome

This is a global prospective, observational, multi-center registry to evaluate the long-term safety profile for participants with short bowel syndrome (SBS) who are treated with teduglutide in a routine clinical setting. The registry will also evaluate the long-term clinical outcomes in participants with SBS. SBS participants treated and not treated with teduglutide will be enrolled.

NCT01990040 Short Bowel Syndrome

MeSH:Short Bowel Syndrome Syndrome

6 Essential Arterial Hypotension and Allostasis Registry

The essential arterial hypotension and allostasis registry is a prospective, observational research that has the purpose of demonstrating that essential blood pressure (BP) disorders and the associated comorbidities are a result of the inappropriate allostatic response to daily life stress. This required a functioning brain orchestrating the evaluation of the threat and choosing the response, this is a mind-mediated phenomenon. If the response is excessive it contributes to high BP, if deficient to low BP, and the BP itself will identify the allostatic pattern, which in turn will play an important role in the development of the comorbidities. To do so, consecutive patients of any age and gender that visit a cardiologist's office in Medellin, Colombia, are recruited. Individuals are classified according to their arterial BP and allostasis and follow them in time to see what kind of diseases develops the most (including BP) in the follow up according to the categorization of the characteristic chosen and after adjustment for confounder's variables. In addition, stress events with their date are registered. HYPOTHESIS The causes of the diseases are multifactorial. Physical, biochemical, psychological, social, and cultural dimensions of development dynamically interact to shape the health development process. A person´s health depends on their: 1. Biological and physiologic systems 2. External and internal environment (a) physical, b) internal behavioural and arousal state as registered by the brain. 3. Their interaction. The allostatic mechanisms to the internal and external stressors (allostatic load) involves a network composed by: 1. Functional systems; mediated by: 1. The Autonomic Nervous System 2. The endocrine system 3. The immune system 2. Structural changes: whenever the internal and/or external stressors are long lasting and/or strength enough, they may induce changes in: 1. Epigenetic, endophenotypes, polyphenism. 2. Plasticity 3. The interaction between a) and b). The network response do not affect exclusively the BP, propitiating the development of comorbidities, which may prompt strategies for prevention, recognition and ultimately, treatment. The allostatic model defines health as a state of responsiveness. The concept of psycho-biotype: The allostasis is the result of both: biological (allostasis) and psychological (psychostasis) abilities. It is proposed that both components behave in similar direction and magnitude. Immune disorders may be associated with the development of cancer. High BP population has a higher sympathetic and lower vagal tone, this has been associated with a decrease in the immune´s system function. Resources and energy depletion: Terms like weathering have been used to describe how exposures to different allostatic loads gradually scrape away at the protective coating that keeps people healthy. It is postulated that High BP individuals have more resources and energy.

NCT02018497 Blood Pressure Depression Panic Attack Fibromyalgia POTS Inappropriate Sinus Tachycardia Coronary Heart Disease Acute Coronary Syndrome (ACS) Acute Myocardial Infarction (AMI) Cerebrovascular Disease (CVD) Transient Ischemic Attack (TIA) Atrial Fibrillation Diabetes Mellitus Cancer Systolic Heart Failure Diastolic Heart Failure Chronic Fatigue Syndrome Syncope Vasovagal Syncope

MeSH:Fatigue Syndrome, Chronic Fibromyalgia Syncope Ischemic Attack, Transient Cerebrovascular Disorders Syncope, Vasovagal Heart Failure Atrial Fibrillation Heart Diseases Myocardial Infarction Acute Coronary Syndrome Hypotension Coron Coronary Disease Tachycardia Heart Failure, Diastolic Heart Failure, Systolic Tachycardia, Sinus Syndrome Panic Disorder

HPO:Atrial fibrillation Carotid sinus syncope Congestive heart failure Hypotension Left ventricular dysfunction Myocardial infarction Paroxysmal atrial fibrillation Right ventricular failure Sinus tachycardia Syncope Tachycardia Transient ischemic attack Vasovagal syncope

7 Repair of Acute Respiratory Distress Syndrome by Stromal Cell Administration (REALIST): An Open Label Dose Escalation Phase 1 Trial Followed by a Randomized, Double-blind, Placebo-controlled Phase 2 Trial (COVID-19)

Acute Respiratory Distress Syndrome (ARDS) causes the lungs to fail due to the collection of fluid in the lungs (pulmonary oedema). ARDS is common in severely ill patients in Intensive Care Units and is associated with a high mortality and a high morbidity in those who survive. ARDS occurs in approximately 20% case of COVID-19 and respiratory failure is the leading cause of mortality. There is a large economic burden with direct healthcare costs, but also indirectly due to the impact on the carer and patient through the patients inability to return to full time employment. There is little evidence for effective drug (pharmacological) treatment for ARDS. There is increasing information that mesenchymal stem cells (MSCs) might be important in treating ARDS. REALIST will investigate if a single infusion of MSCs will help in the treatment of ARDS. The first step will be to first of all determine what dose of MSCs is safe and then divide patients suffering from ARDS into two groups, one of which will get MSCs and the other a harmless dummy (or placebo) infusion, who will then be followed up to determine if lung function improves. If effective this may lead to further research to determine if MSCs are effective in patients with ARDS.

NCT03042143 Acute Respiratory Distress Syndrome Biological: Human umbilical cord derived CD362 enriched MSCs Biological: Placebo (Plasma-Lyte 148)

MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

8 Implementation of Lung Protective Ventilation in Patients With Acute Respiratory Failure

This is a quality improvement study with the purpose of observing and measuring the effects of implementation of a proven standardized lung protective ventilation protocol in the new electronic medical record system iCentra across all Intermountain Healthcare hospitals. Approximately 14,000 records will be accessed for this study from a database of mechanically ventilated patients established for quality improvement purposes. The investigators hypothesize that implementation of a standardized computerized lung protective ventilation protocol across all Intermountain Healthcare hospitals will be feasible, will decrease initial tidal volumes to the target 6 ml/kg PBW, and will improve outcomes. The objectives of this study are to: - Determine if the implementation of lung protective ventilation (with a 6 ml/kg PBW tidal volume ventilation protocol on initiation of mechanical ventilation) improves outcomes in patients with acute respiratory failure requiring mechanical ventilation - Determine if the implementation of lung protective ventilation (with a 6 ml/kg PBW tidal volume ventilation protocol on initiation of mechanical ventilation) improves outcomes in the sub-group of patients with the acute respiratory distress syndrome (ARDS) - Measure compliance with the implementation of a computerized lung protective ventilation protocol at 12 Intermountain Healthcare hospitals

NCT03225807 Acute Respiratory Distress Syndrome ARDS Respiratory Distress Syndrome, Acute Respiratory Insufficiency Respiratory Distress Syndrome Shock Lung Severe Acute Respiratory Syndrome

MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Pulmonary Valve Insufficiency Syndrome

HPO:Pulmonary insufficiency

9 A Phase I Study to Determine the Safety and Immunogenicity of the Candidate Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Vaccine ChAdOx1 MERS in UK Healthy Adult Volunteers

This is a clinical trial in which healthy volunteers will be administered an experimental MERS vaccine. The vaccine ChAdOx1 MERS will be administered alone both as a single administration and with a homologous prime-booster.

NCT03399578 MERS (Middle East Respiratory Syndrome) Biological: ChAdOx1 MERS

MeSH:Coronavirus Infections Syndrome

10 Streptokinase Versus Unfractionated Heparin Nebulization in Patients With Severe Acute Respiratory Distress Syndrome (ARDS): A Partially Randomized Controlled Trial

Background: Intra-alveolar clotting and alveolar collapse in ARDS is due to alveolar capillaries epithelial and leakage. Subsequently, collapse induces hypoxemia that is resistant to recruitment (RM). Heparin and Streptokinase may prevent or dissolve intra-alveolar fibrin clot respectively helping alveolar re-expansion. We examined and compared the effect of nebulizing Heparin versus Streptokinase on reversing this pathology. Methods: Sixty severe ARDS (PaO2/FiO2<100) patients and failure of RM, prone position (PP) and neuromuscular block (NMB) were partially randomised into Group (I): (n=20) received nebulized Heparin 10000 IU/4h. Group (II): (n=20) received nebulized Streptokinase 250,000 IU/4h. Group (III): (n=20) received conservative management. Randomization to either Heparin or Streptokinase groups was applied to patients whom guardian accepted participation, while those who declined participation were followed-up as a control. The primary outcome was the change in PaO2/FiO2; the secondary outcomes included the change in compliance, plateau pressure, ventilation-off days, coagulation and ICU mortality.

NCT03465085 Acute Respiratory Distress Syndrome Severe Acute Respiratory Syndrome Drug: Unfractionated heparin Drug: Streptokinase

MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Distress Syndro Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

11 An Open-label, Standard Therapy as a Controlled, Multicenter Phase 2 Study to Evaluate the Efficacy and Safety of HLCM051(MultiStem) in Patients With Acute Respiratory Distress Syndrome (ARDS) Caused by Pneumonitis

The primary object of this clinical study is to investigate the efficacy of HLCM051 in patients with ARDS caused by pneumonitis.

NCT03807804 Respiratory Distress Syndrome, Adult Biological: HLCM051

MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

12 Outcomes Mandate National Integration With Cannabis as Medicine

This will be a multistate, multicenter clinical study to determine the efficacy and safety of medical cannabis for a wide variety of chronic medical conditions.

NCT03944447 Chronic Pain Chronic Pain Syndrome Chronic Pain Due to Injury Chronic Pain Due to Trauma Fibromyalgia Seizures Hepatitis C Cancer Crohn Disease HIV/AIDS Multiple Sclerosis Traumatic Brain Injury Sickle Cell Disease Post Traumatic Stress Disorder Tourette Syndrome Ulcerative Colitis Glaucoma Epilepsy Inflammatory Bowel Diseases Parkinson Disease Amyotrophic Lateral Sclerosis Chronic Traumatic Encephalopathy Anxiety Depression Insomnia Autism Opioid-use Disorder Bipolar Disorder Covid19 SARS-CoV Infection Drug: Cannabis, Medical

MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Fibromyalgia Crohn Disease Inflammatory Bowel Diseases Parkinson Disease Multiple Sclerosis Brain Injuries Brain Injuries, Traumatic Seizures Motor Neuron Disease Amyotrophic Lateral Sclerosis Brain Diseases Tourette Syndrome Chronic Traumatic Encephalopathy Anemia, Sickle Cell Disease Syndrome Sclerosis Chronic Pain Stress Disorders, Traumatic Bipolar Disorder Stress Disorders, Post-Traumatic Wounds and Injuries

HPO:Abnormal anterior horn cell morphology Amyotrophic lateral sclerosis Bilateral tonic-clonic seizure Bipolar affective disorder Chronic pain Crohn's disease Encephalopathy Focal-onset seizure Generalized-onset seizure Inflammation of the large intestine Mania Seizure

13 Double-blind, Placebo-controlled Study With an Open Dose Selection Period for Assessing the Safety and Immunogenicity of the Drug "BVRS-GamVac-Combi", a Combined Vector Vaccine for the Prevention of the Middle East Respiratory Syndrome, Lyophilisate for the Preparation of a Solution for Intramuscular Administration, With the Participation of Healthy Volunteers

The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreak. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of ~34.5%. The aim of the study is to assess the safety and immunogenicity of heterologous adenoviral-based vaccine against MERS - BVRS-GamVac-Combi.

NCT04128059 MERS (Middle East Respiratory Syndrome) MERS Drug: BVRS-GamVac-Combi Other: placebo

MeSH:Coronavirus Infections Syndrome

14 Double-blind, Placebo-controlled Study With an Open Dose Selection Period for Assessing the Safety and Immunogenicity of the Drug "BVRS-GamVac", a Vector Vaccine for the Prevention of the Middle East Respiratory Syndrome, Lyophilisate for the Preparation of a Solution for Intramuscular Administration, With the Participation of Healthy Volunteers

The Middle East respiratory syndrome coronavirus (MERS-CoV) was identified in 2012 during the first Middle East respiratory syndrome (MERS) outbreak. MERS-CoV causes an acute lower-respiratory infection in humans, with a fatality rate of ~34.5%. The aim of the study is to assess the safety and immunogenicity of adenoviral-based vaccine against MERS - BVRS-GamVac.

NCT04130594 MERS (Middle East Respiratory Syndrome) MERS Biological: BVRS-GamVac Other: placebo

MeSH:Coronavirus Infections Syndrome

15 A Phase Ib Study to Determine the Safety and Immunogenicity of the Candidate Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Vaccine ChAdOx1 MERS in Healthy Adult Middle Eastern Volunteers

A phase Ib study to determine the safety and immunogenicity of the candidate Middle East Respiratory Syndrome Coronavirus (MERS-CoV) vaccine ChAdOx1 MERS in healthy adult Middle Eastern volunteers

NCT04170829 Middle East Respiratory Syndrome Coronavirus Biological: ChAdOx1 MERS

MeSH:Coronavirus Infections Syndrome

16 Pharmacokinetics, Pharmacodynamics, and Safety Profile of Understudied Drugs

The study investigators are interested in learning more about how drugs, that are given to children by their health care provider, act in the bodies of children and young adults in hopes to find the most safe and effective dose for children. The primary objective of this study is to evaluate the PK of understudied drugs currently being administered to children per SOC as prescribed by their treating provider.

NCT04278404 Coronavirus Infection (COVID-19) Pulmonary Arterial Hypertension Urinary Tract Infections in Children Hypertension Pain Hyperphosphatemia Primary Hyperaldosteronism Edema Hypokalemia Heart Failure Hemophilia Menorrhagia In Insomnia Pneumonia Skin Infection Arrythmia Asthma in Children Bronchopulmonary Dysplasia Adrenal Insufficiency Fibrinolysis; Hemorrhage Attention Deficit Hyperactivity Disorder Multisystem Inflammatory Syndrome in Children (MIS-C) Kawasaki Disease Coagulation Disorder Down Syndrome Drug: The POP02 study is collecting bodily fluid samples (i.e., whole blood, effluent samples) of children prescribed the following drugs of interest per standard of care:

MeSH:Infection Communicable Diseases Urinary Tract Infections Coronavirus Infections Severe Acute Respiratory Syndrome Bronchopulmonary Dysplasia Down Syndrome Menorrhagia Hypertension Hemostatic Disorders Mucocutaneous Lymph Node Syndrome Blood Coagulation Disorders Hyperphosphatemia Hypokalemia Adrenal Insufficiency Hyperaldosteronism Disease Syndrome Hemorrhage Attention Deficit Disorder with Hyperactivity

HPO:Abnormality of coagulation Abnormality of the coagulation cascade Adrenal insufficiency Attention deficit hyperactivity disorder Hyperaldosteronism Hyperphosphatemia Hypertension Hypokalemia Menorrhagia Primary hyperaldosteronism

17 Nitric Oxide Gas Inhalation Therapy for Severe Acute Respiratory Syndrome Due to COVID-19.

The investigators will enroll 102 patients with a confirmed diagnosis of COVID-19. Patients will be randomized to receive either inhaled nitric oxide (per protocol) or placebo. ICU Standards of care will be the institution's own protocols (such as ventilation strategies and use and dose of antivirals and antimicrobials, steroids, inotropic and vasopressor agents).

NCT04290871 Coronavirus SARS (Severe Acute Respiratory Syndrome) Drug: Nitric Oxide Gas

MeSH:Coronavirus Infe Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome

18 Clinical Application of Stem Cell Educator Therapy for the Treatment of Viral Inflammation Caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Currently, the growing epidemic of a new coronavirus infectious disease (Covid-19) is wreaking havoc worldwide, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a RNA virus that display high similarity in both genomic and proteomic profiling with SARS-CoV that first emerged in humans in 2003 in China. Therefore, preventing and controlling the pandemic occurrences are extremely urgent as a global top priority. Due to the lack of effective antiviral drugs, patients may be treated by only addressing their symptoms such as reducing fever. Clinical autopsies from SARS-CoV-infected patients demonstrated that there were major pathological changes in the lungs, immune organs, and small systemic blood vessels with vasculitis. However, the detection of SARS-CoV were primarily found in the lung and trachea/bronchus, but was undetectable in spleen, lymph nodes, bone marrow, heart and aorta, highlighting the overreaction of immune responses induced by viral infection were really harmful, resulting in the pathogenesis of lungs, immune organs, and small systemic blood vessels. To this respect, immune modulation strategy may be potentially beneficial to enhance anti-viral immunity and efficiently reduce the viral load, improve clinical outcomes, expedite the patient recovery, and decline the rate of mortality in patients after being infected with SARS-CoV-2. Tianhe Stem Cell Biotechnologies Inc. has developed a novel globally-patented Stem Cell Educator (SCE) technology designed to reverse the autoimmune response in Type 1 diabetes (T1D), Alopecia Areata (AA) and other autoimmune diseases. SCE therapy uses human multipotent cord blood stem cells (CB-SC) from human cord blood. Their properties distinguish CB-SC from other known stem cell types, including mesenchymal stem cells (MSC) and hematopoietic stem cells (HSC). Several clinical studies show that SCE therapy functions via CB-SC induction of immune tolerance in autoimmune T cells and restore immune balance and homeostasis in patients with T1D, AA and other inflammation-associated diseases. To correct the overreaction of overreaction of immune responses, the investigators plan to treat SARS-CoV-2 patients with Stem Cell Educator therapy.

NCT04299152 Severe Acute Respiratory Syndrome (SARS) Pneumonia Combination Product: Stem Cell Educator-Treated Mononuclear Cells Apheresis

MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome Inflammation

HPO:Pneumonia

19 Nitric Oxide Gas Inhalation Therapy for Mechanically Ventilated Patients With Severe Acute Respiratory Syndrome Caused by SARS-CoV2: a Randomized Clinical Trial.

Severe acute respiratory syndrome (SARS-CoV2) due to novel Coronavirus (2019-nCoV) related infection (COVID-19) is characterized by severe ventilation perfusion mismatch leading to refractory hypoxemia. To date, there is no specific treatment available for 2019-nCoV. Nitric oxide is a selective pulmonary vasodilator gas used in as a rescue therapy in refractory hypoxemia due to acute respiratory distress syndrome (ARDS). In-vitro and clinical evidence indicate that inhaled nitric oxide gas (iNO) has also antiviral activity against other strains of coronavirus. The primary aim of this study is to determine whether inhaled NO improves oxygenation in patients with hypoxic SARS-CoV2. This is a multicenter single-blinded randomized controlled trial with 1:1 individual allocation

NCT04306393 SARS (Severe Acute Respiratory Syndrome) Coronavirus Drug: Nitric Oxide Gas

MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome

20 A Retrospective Study of Evaluating Safety and Efficacy of Tocilizumab Compared to Continuous Renal Replacement Therapy in Controlling CRS Triggered by COVID-19

Some patients infected with the COVID-19 can develop uncontrolled immune response, leading to potentially life-threatening damage to lung tissue. Tocilizumab was first approved by the U.S. FDA in 2010 for rheumatoid arthritis and might now be used to treat serious COVID-19 patients with lung damage, according to China's National Health Commission updated its treatment guidelines in 7th version.Continuous Renal Replacement Therapy (CRRT) was recommended by China's National Health Commission treatment guidelines in 1st-7th version to control sever COVID-19 patients.

NCT04306705 Covid-19 SARS Cytokine Storm Cytokine Release Syndrome Tocilizumab Drug: Tocilizumab Other: Standard of care Procedure: Continuous renal replacement therapy

MeSH:Syndrome

21 Uppsala Intensive Care Study of Mechanisms for Organ Dysfunction in Covid-19

The study aims to investigate organ dysfunction and biomarkers in patients with suspected or verified COVID-19 during intensive care at Uppsala University Hospital.

NCT04316884 COVID-19 Organ Dysfunction Syndrome Sepsis Organ Dysfunction Syndrome, Multiple Septic Shock Acute Kidney Injury Acute Respiratory Distress Syndrome

MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Acute Kidney Injury Syndrome Systemic Inflammatory Response Syndrome Multiple Organ Failure

HPO:Acute kidney injury

22 Efficacy and Safety of Chloroquine Diphosphate for the Treatment of Hospitalized Patients With Severe Acute Respiratory Syndrome Secondary to SARS-CoV2: a Phase IIb, Double-blind, Randomized Adaptive Clinical Trial

In December 2019, the Municipal Health Committee of Wuhan, China, identified an outbreak of viral pneumonia of unknown cause. This new coronavirus was called SARS-CoV-2 and the disease caused by that virus, COVID-19. Recent numbers show that 222,643 infections have been diagnosed with 9115 deaths, worldwide. Currently, there are no approved therapeutic agents available for coronaviruses. In this scenario, the situation of a global public health emergency and evidence about the potential positive effect of chloroquine (CQ) in most coronaviruses, including SARS-CoV-1, and recent data on small trials on SARS-CoV-2, the investigators intend to investigate the efficacy and the safety of CQ diphosphate in the treatment of hospitalized patients with severe acute respiratory syndrome in the scenario of SARS-CoV2. Preliminary in vitro studies and uncontrolled trials with low number of patients of CQ repositioning in the treatment of COVID-19 have been encouraging. The main hypothesis is that CQ diphosphate will reduce mortality in 50% in those with severe acute respiratory syndrome infected by the SARS-COV2. Therefore, the main objective is to assess whether the use of chloroquine diphosphate reduces mortality by 50% in the study population. The primary outcome is mortality in day 28 of follow-up. According to local contingency plan, developed by local government for COVID-19 in the State of Amazonas, the Hospital Pronto-Socorro Delphina Aziz, located in Manaus, is the reference unit for the admission of serious cases of the new virus. The unit currently has 50 ICU beds, with the possibility of expanding to 335 beds, if needed. The hospital also has trained multiprofessional human resources and adequate infrastructure. In total, 440 participants (220 per arm) will receive either high dose chloroquine 600 mg bid regime (4x150 mg tablets, every 12 hours, D1-D10) or low dose chloroquine 450mg bid regime (3x150mg tablets + 1 placebo tablet every 12 hours on D1, 3x150mg tablets + 1 placebo followed by 4 placebo tablets 12h later from D2 to D5, and 4 placebo tablets every 12 hours, D6-D10). Placebo tablets were used to standardize treatment duration and blind research team and patients. All drugs administered orally (or via nasogastric tube in case of orotracheal intubation). Both intervention and placebo drugs will be produced by Farmanguinhos. Clinical and laboratory data during hospitalization will be used to assess efficacy and safety outcomes.

NCT04323527 SARS-CoV Infection Severe Acute Respiratory Syndrome (SARS) Pneumonia Drug: Chloroquine diphosphate

MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome

HPO:Pneumonia

23 Prolonged Low Doses of Methylprednisolone for Patients With COVID-19 Severe Acute Respiratory Syndrome

COVID-19 infection is overwhelming Italian healthcare. There is an urgent need for a solution to the lack of ICU beds and increasing deaths day after day. A recent retrospective Chinese paper (JAMA Intern Med, online March 13, 2020) showed impressive positive effect of methylprednisolone (MP) on survival of SARS-CoV-2 critically ill patients. Moreover, the Italian Infectious Disease leading institution guidelines for COVID-19 clinical management included as an option for patients with "incipient worsening of respiratory functions" methylprednisolone treatment at an approximate dose of 80mg. The main objective of this multi-centre observational trial is to analyse the association of low dose prolonged infusion of methylprednisolone (MP) for patients with severe acute respiratory syndrome with composite primary end-point (ICU referral, need for intubation, in-hospital death at day 28).

NCT04323592 Severe Acute Respiratory Syndrome (SARS) Pneumonia Coronavirus Infections ARDS, Human Drug: Methylprednisolone Other: standard care

MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Pneumonia Respiratory Distress Syndrome, Adult Syndrome

HPO:Pneumonia

24 Integrated Distance Management Strategy for Patients With Cardiovascular Disease (Ischaemic Coronary Artery Disease, High Blood Pressure, Heart Failure) in the Context of the COVID-19 Pandemic

Management of known patients with cardiovascular disease (in particular the whole spectrum of atherosclerotic ischaemic coronary artery disease, essential hypertension under treatment, and also patients with chronic heart failure under medication) and with other associated chronic pathologies, with obvious effects on the management of the pandemic with modern / distance means (e-Health) of patients at high risk of mortality in contact with coronavirus. Given the Covid-19 Pandemic, all the above complex cardiovascular patients are under the obligation to stay in the house isolated and can no longer come to standard clinical and paraclinical monitoring and control visits. Therefore, a remote management solution (tele-medicine) of these patients must be found. The Investigators endeavour is to create an electronic platform to communicate with these patients and offer solutions for their cardiovascular health issues (including psychological and religious problems due to isolation). The Investigators intend to create this platform for communicating with a patient and stratify their complaints in risk levels. A given specialist will sort and classify their needs on a scale, based on specific algorithms (derived from the clinical European Cardiovascular Guidelines), and generate specific protocols varying from 911 like emergencies to cardiological advices or psychological sessions. These could include medication changing of doses, dietary advices or exercise restrictions. Moreover, in those patients suspected of COVID infection, special assistance should be provided per protocol.

NCT04325867 Angina Pectoris Acute Coronary Syndrome Coronary Syndrome Coronary Artery Disease Angioplasty Stent Restenosis Hypertension Heart Failure, Systolic Depression, Anxiety Covid-19 Isolation, Social Other: Tele-medicine platform

MeSH:Heart Failure Coronary Artery Disease Myocardial Ischemia Coronary Disease Acute Coronary Syndrome Angina Pectoris Heart Failure, Systolic Syndrome Cardiovascular Diseases

HPO:Abnormality of the cardiovascular system Angina pectoris Congestive heart failure Coronary artery atherosclerosis Left ventricular dysfunction Myocardial infarction Right ventricular failure

25 Efficacy of Hydroxychloroquine for Post-exposure Prophylaxis (PEP) to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection Among Adults Exposed to Coronavirus Disease (COVID-19): a Blinded, Randomized Study

This is a clinical study for the prevention of SARS-CoV-2 infection in adults exposed to the virus. This study will enroll up to 2000 asymptomatic men and women 18 to 80 years of age (inclusive) who are close contacts of persons with laboratory confirmed SARS-CoV-2 or clinically suspected COVID-19. Eligible participants will be enrolled and randomized to receive the intervention or placebo at the level of the household (all eligible participants in one household will receive the same intervention).

NCT04328961 COVID-19 Corona Virus Infection SARS (Severe Acute Respiratory Syndrome) SARS-CoV-2 Drug: Hydroxychloroquine Sulfate Drug: Ascorbic Acid

MeSH:Infection Severe Acute Respiratory Syndrome Coronavirus Infections Syndrome

26 Safety and Efficacy Study of Human Embryonic Stem Cells Derived M Cells (CAStem) for the Treatment of Severe COVID-19 Associated With or Without Acute Respiratory Distress Syndrome (ARDS)

A phase1/2, open label, dose escalation, safety and early efficacy study of CAStem for the treatment of severe COVID-19 associated with or without ARDS.

NCT04331613 COVID-19 Acute Respiratory Distress Syndrome Virus; Pneumonia Acute Lung Injury Biological: CAStem

MeSH:Pneumonia, Viral Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome

HPO:Pneumonia

27 Cell Therapy Using Umbilical Cord-derived Mesenchymal Stromal Cells in SARS-CoV-2-related 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.

NCT04333368 Severe Acute Respiratory Syndrome Coronavirus 2 Severe Acute Respiratory Distress Syndrome Biological: Umbilical cord Wharton's jelly-derived human Other: NaCl 0.9%

MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

28 Treatment of Severe Acute Respiratory Syndrome Caused by COVID-19 With Ruxolitinib

In December 2019, a new virus emerged in Wuhan, China rapidly becoming a pandemic with registered cases above 800,000 around the world. The virus is now known as SARS-CoV2 calling its disease coronavirus-19 or COVID-19. The mortality of the virus has been reported around 2-10% and its causes because of the proinflammatory immune response generated on the host. The cytokines involved in the immune response to COVID-19 are IL-1, IL-2, IL4, IL-6, IL-10, IL-12, IL-13, IL-17, GCSF, MCSF, IP-10, MCP-1, MIP-1α, HGF, IFN-γ y TNF-α. Ruxolitinib is an inhibitor of JAK 1/2 which is responsable for multiple cellular signals including the proinflammatory IL-6. Ruxolitinib works as and immunomodulator decreasing the cytotoxic T lymphocytes and increasing the Treg cells. This study is intended to stop the disregulated immune response caused by COVID-19 that generates the pneumonia and subsequent severe acute respiratory syndrome.

NCT04334044 COVID-19 Severe Acute Respiratory Syndrome Coronavirus 2 Drug: Ruxolitinib Oral Tablet

MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome

29 PRAETORIAN-COVID: A Double-blind, Placebo-controlled Randomized Clinical Trial With Valsartan for PRevention of Acute rEspiraTORy dIstress Syndrome in hospitAlized patieNts With SARS-COV-2 (COVID-19) Infection Disease

Rationale: The current SARS-CoV-2 pandemic has a high burden of morbidity and mortality due to development of the so-called acute respiratory distress syndrome (ARDS). The renin-angiotensin-system (RAS) plays an important role in the development of ARDS. ACE2 is one of the enzymes involved in the RAS cascade. Virus spike protein binds to ACE2 to form a complex suitable for cellular internalization. The downregulation of ACE2 results in the excessive accumulation of angiotensin II, and it has been demonstrated that the stimulation of the angiotensin II type 1a receptor (AT1R) increases pulmonary vascular permeability, explaining the increased lung pathology when activity of ACE2 is decreased. Currently available AT1R blockers (ARBs) such as valsartan, have the potential to block this pathological process mediated by angiotensin II. There are presently two complementary mechanisms suggested: 1) ARBs block the excessive angiotensin-mediated AT1R activation, and 2) they upregulate ACE2, which reduces angiotensin II concentrations and increases the production of the protective vasodilator angiotensin 1-7. In light of the above, ARBs may prevent the development of ARDS and avert morbidity (admission to intensive care unit (ICU) and mechanical ventilation) and mortality. Objective: To investigate the effect of the ARB valsartan in comparison to placebo on the occurrence of one of the following items, within 14 days of randomization:1) ICU admission; 2) Mechanical ventilation; 3) Death. Study design: A double-blind, placebo-controlled 1:1 randomized clinical trial Study population: Adult hospitalized SARS-CoV-2-infected patients (n=651). Intervention: The active-treatment arm will receive valsartan in a dosage titrated to blood pressure up to a maximum of 160mg b.i.d. and the placebo arm will receive a matching placebo also titrated to blood pressure. Treatment duration will be 14 days or up to hospital discharge < 14 days or occurrence of the primary endpoint if < 14 days. Main study endpoint: The primary study endpoint is the occurrence within 14 days of randomization of either: 1) ICU admission; 2) Mechanical ventilation; 3) Death.

NCT04335786 Acute Respiratory Distress Syndrome SARS-CoV-2 COVID COVID-19 Severe Acute Respiratory Syndrome Drug: Valsartan (Diovan) Drug: Placebo oral tablet

MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

30 Phase IIb Study to Evaluate the Efficacy and Safety of Chloroquine Diphosphate in the Treatment of Patients With Comorbidities, Without Severe Acute Respiratory Syndrome, Under the New Coronavirus (SARS-CoV2): a Double-blind, Randomized, Placebo-controlled Clinical Trial

This is a double-blind, randomized, placebo-controlled clinical trial. A total of 210 individuals aged over 18 years old, without a diagnosis of severe respiratory disease, who came to the study site with clinical and radiological suspicion of SARS-CoV2, will be randomized into two treatment groups at a 1:1 ratio to receive a 5-day CQ diphosphate tablets or placebo (tablet without active ingredient produced with the same physical characteristics).

NCT04342650 COVID-19 SARS-CoV Infection Severe Acute Respiratory Syndrome (SARS) Pneumonia Clinical Trial Drug: Chloroquine Diphosphate Drug: Placebo oral tablet

MeSH:Infection Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome

HPO:Pneumonia

31 Efficacy of Injectable Methylprednisolone Sodium Succinate in the Treatment of Patients With Signs of Severe Acute Respiratory Syndrome Under the New Coronavirus (SARS-CoV2): a Phase IIb, Randomized, Double-blind, Placebo-controlled, Clinical Trial.

This is a double-blind, randomized, placebo-controlled, phase IIb clinical trial to assess the efficacy of injectable methylprednisolone sodium succinate (MP) in patients with severe acute respiratory syndrome (SARS) in COVID-19 infection. A total of 416 individuals of both sexes, aged over 18 years old, with symptoms suggestive or confirmed diagnosis of severe acute respiratory syndrome (SARS), hospitalized at the Hospital and Pronto-Socorro Delphina Rinaldi Abdel Aziz (HPSDRAA), with clinical and radiological findings suggestive of SARS-CoV2 infection, will be randomized at a 1:1 ration to receive either MP (0.5mg/kg of weight, twice daily, for 5 days) or placebo (saline solution, twice daily, for 5 days).

NCT04343729 SARS-CoV Infection Severe Acute Respiratory Syndrome (SARS) Pneumonia Drug: Methylprednisolone Sodium Succinate Drug: Placebo solution

MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Pneumonia Syndrome

HPO:Pneumonia

32 Dexamethasone Combined With Hydroxychloroquine Compared to Hydroxychloroquine Alone for Treatment of Severe Acute Respiratory Distress Syndrome Induced by Coronavirus Disease 19 (COVID-19): a Multicentre, Randomised Controlled Trial

Single blind randomized clinical trial designed to evaluate the efficacy of the combination of hydroxychloroquine and dexamethasone as treatment for severe Acute Respiratory Distress Syndrome (ARDS) related to coronavirus disease 19 (COVID-19). We hypothesize that dexamethasone (20 mg for 5 days followed by 10 mg for 5 days) combined with 600 mg per day dose of hydroxychloroquine for 10 days will reduce the 28-day mortality compared to hydroxychloroquine alone in patients with severe ARDS related COVID-19.

NCT04347980 Respiratory Distress Syndrome, Adult COVID-19 Drug: Dexamethasone and Hydroxychloroquine Drug: Hydroxychloroquine

MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

33 Value of Early Treatment With Polyvalent Immunoglobulin in the Management of Acute Respiratory Distress Syndrome Associated With SARS-CoV-2 Infections

As of 30/03/2020, 715600 people have been infected with COVID-19 worldwide and 35500 people died, essentially due to respiratory distress syndrome (ARDS) complicated in 25% of the with acute renal failure. No specific pharmacological treatment is available yet. The lung lesions are related to both the viral infection and to an intense inflammatory reaction. Because of it's action, as an immunomodulatory agent that can attenuate the inflammatory reaction and also strengthen the antiviral response, it is proposed to evaluate the effectiveness and safety of intravenous immunoglobulin administration (IGIV) in patients developing ARDS post-SARS-CoV2. IGIV modulates immunity, and this effect results in a decrease of pro-inflammatory activity, key factor in the ARDS related to the COVID-19. It should be noted that IGIV is part of the treatments in various diseases such as autoimmune and inflammatory diffuse interstitial lung diseases. In addition, they have been beneficial in the post-influenza ARDS but also have been in 3 cases of post-SARS-CoV2 ARDS. IGIV is a treatment option because it is well tolerated, especially concerning the kidney. These elements encourage a placebo-controlled trial testing the benefit of IGIV in ARDS post-SARS-CoV2.

NCT04350580 Acute Respiratory Distress Syndrome COVID-19 Drug: Human immunoglobulin Drug: Placebo

MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

34 Evaluation of Respiratory Mechanics and Lung Recruitment in Patients With SARS-CoV-2 Associated Acute Respiratory Distress Syndrome

The aim of this observationnal study is to describe respiratory mechanics and lung recruitement in patients with SARS-CoV-2 Associated Acute Respiratory Distress Syndrome who underwent invasive ventilation on endotracheal tube, admitted to the medical ICU of Angers university hospital . Statics measurements of respiratory system compliance were performed at 2 differents levels of PEEP (15 cmH2O and 5 cmH2O). The recruited volume is computed as the difference between the volume expired from PEEP 15 to 5 cmH2O and the volume predicted by compliance at PEEP 5 cmH2O . The recruitment-to-Inflation (R/I) ratio (i.e. the ratio between the recruited lung compliance and CRS at PEEP 5 cmH2O) is used to assess lung recruitability. A R/I ratio value higher than or equal to 0.5 was used to define highly recruiter patients.

NCT04350710 Acute Respiratory Distress Syndrome COVID Other: PEEP trial

MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

35 Efficacy and Safety of Aerosolized Intra-tracheal Dornase Alfa Administration in Patients With COVID19-induced Acute Respiratory Distress Syndrome (ARDS)

This study plans to learn more about the effects of Dornase Alfa in COVID19 (coronavirus disease of 2019) patients, the medical condition caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Dornase Alfa is a FDA-approved drug for the treatment of cystic fibrosis, which facilitates mucus clearance by cutting apart neutrophil-derived extracellular double-stranded DNA. This study intends to define the impact of aerosolized intra-tracheal Dornase Alfa administration on the severity and progression of acute respiratory distress syndrome (ARDS) in COVID-19 patients. This drug might make lung mucus thinner and looser, promoting improved clearance of secretions and reduce extracellular double-stranded DNA-induced hyperinflammation in alveoli, preventing further damage to the lungs. The study will recruit mechanically ventilated patients hospitalized in ICU who have been diagnosed with COVID-19 and meet ARDS criteria. It is a prospective, randomized, controlled, multicentric, open-label clinical trial. The goal is to recruit 100 patients.

NCT04355364 COVID-19 Acute Respiratory Distress Syndrome Drug: Dornase Alfa Inhalation Solution [Pulmozyme] Procedure: standard procedure

MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

36 SOLIRIS® (Eculizumab) for the Treatment of Participants With Coronavirus Disease 2019 (COVID 19) - An Expanded Access Program for Hospital-based Emergency Treatment

This protocol provides access to eculizumab treatment for participants with severe COVID-19.

NCT04355494 COVID-19 Pneumonia, Viral Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS) Biological: eculizumab

MeSH:Pneumonia, Viral Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome

HPO:Pneumonia

37 Umbilical Cord-derived Mesenchymal Stem Cells for COVID-19 Patients With Acute Respiratory Distress Syndrome (ARDS)

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).

NCT04355728 Corona Virus Infection ARDS ARDS, Human Acute Respiratory Distress Syndrome COVID-19 Biological: Umbilical Cord Mesenchymal Stem Cells + Heparin along with best supportive care. Other: Vehicle + Heparin along with best supportive care

MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

38 Fibrinolytic Therapy to Treat ARDS in the Setting of COVID-19 Infection: A Phase 2a Clinical Trial

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.

NCT04357730 Severe Acute Respiratory Syndrome Respiratory Failure Acute Respiratory Distress Syndrome Drug: Alteplase 50 MG [Activase] Drug: Alteplase 100 MG [Activase]

MeSH:Severe Acute Respiratory Syndrome Coron Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Syndrome

39 Impact of Dexmedetomidine Infusion on the Time Course and Outcomes of Acute Respiratory Distress Syndrome (ARDS) in Patients Affected by the SARS-CoV-2 (COVID-19) Admitted to Critical Care Unit

A continuous infusion of Dexmedetomidine (DEX) will be administered to 80 patients admitted to Critical Care because of signs of Respiratory Insufficiency requiring non-invasive ventilation. Measurements of respiratory performance and quantification of cellular and molecular inflammatory mediators. The primary outcome will be the avoidance of mechanical ventilation with secondary outcomes duration of mechanical ventilation, avoidance of delirium after sedation and association of mediators of inflammation to outcomes. Outcomes will be compared to a matched historical control (no DEX) series

NCT04358627 Acute Respiratory Distress Syndrome Inflammation Dexmedetomidine Cytokine Storm Delirium, Emergence Drug: Dexmedetomidine Injectable Product

MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Delirium Emergence Delirium Syndrome Inflammation

40 Evaluation of Prone Position in Conscious Patients on Nasal High-flow Oxygen Therapy for COVID-19 Disease Induced Acute Respiratory Distress Syndrome

Acute Respiratory Distress Syndrome (ARDS) induces high mortality, particularly in the context of COVID-19 disease. Preliminary data from patients with ARDS related to COVID-19 disease appear to show significant effectiveness of prone positioning in intubated patients in terms of oxygenation as well as nasal high flow therapy before intubation. It should be noted that in Jiangsu province, secondarily affected, nasal high flow combined with the prone position was successfully integrated into care protocols. The investigators hypothesize that the combined application of nasal high flow and prone positioning can significantly improve the outcome of patients suffering from COVID-19 pneumonia by reducing the need for tracheal intubation and associated therapeutics such as sedation and paralysis, resulting in both individual and collective benefits in terms of use of scarce critical care resources. Investigators hypothesize that the combined application of nasal high-flow and prone positioning can significantly improve the outcome of patients suffering from COVID-19 pneumonia by reducing the need for intubation and associated therapeutics such as sedation and paralysis, resulting in both individual and collective benefits in terms of use of scarce critical care resources.

NCT04358939 Acute Respiratory Distress Syndrome COVID-19 Other: Prone decubitus

MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

41 The Effect of Prone Positioning on Lung Aeration and Ventilation-perfusion Matching in Mechanically Ventilated Patients With Coronavirus Disease Related Acute Respiratory Distress Syndrome

The consensus therapeutic strategy implies that COVID patients with acute lung injury due to coronavirus are routinely placed in prone position in an attempt to improve oxygenation by increasing ventilation homogeneity. The purpose of the study is to quantify with the electrical impedance tomography (EIT) the changes in the ventilation and aeration in the dorsal regions of the lung when the patient is placed in prone position.

NCT04359407 Severe Acute Respiratory Syndrome Coronavirus 2 Electric Impedance Prone Positioning Other: Prone positioning

MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Syndrome

42 COVID-19: Ruxolitinib for the Treatment of cytokinE Storm resPiratory dIstREss Syndrome. RESPIRE Study

It is an observational, cohort, retrospective, monocentric, non-profit study. The primary objective is to evaluate the efficacy and safety of ruxolitinib in acute respiratory distress syndrome in patients with SARS-CoV-2 COVID-19 with rapid deterioration of respiratory parameters in the last 12 hours.

NCT04361903 Severe Acute Respiratory Syndrome Coronavirus 2 Drug: Ruxolitinib Oral Tablet

MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Syndrome

43 Phase 3 Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Canakinumab on Cytokine Release Syndrome in Patients With COVID-19-induced Pneumonia (CAN-COVID)

This is a multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of canakinumab plus standard-of-care (SOC) compared with placebo plus SOC in patients with COVID-19-induced pneumonia and cytokine release syndrome (CRS).

NCT04362813 Pneumonia and Cytokine Release Syndrome (Covid-19) Drug: Canakinumab Drug: Placebo

MeSH:Pneumonia Syndrome

HPO:Pneumonia

44 Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19

Ideal new treatments for Novel Coronavirus-19 (COVID-19) would help halt the progression disease in patients with mild disease prior to the need for artificial respiration (ventilators), and also provide a rescue treatment for patients with severe disease, while also being affordable and available in quantities sufficient to treat large numbers of infected people. Low doses of Naltrexone, a drug approved for treating alcoholism and opiate addiction, as well as Ketamine, a drug approved as an anesthetic, may be able to interrupt the inflammation that causes the worst COVID-19 symptoms and prove an effective new treatment. This study will investigate their effectiveness in a randomized, blinded trial versus standard treatment plus placebo.

NCT04365985 COVID-19 Acute Respiratory Distress Syndrome Severe Acute Respiratory Syndrome (SARS) Coronavirus Infections Drug: Naltrexone Drug: Ketamine Other: Placebo

MeSH:Coronavirus Infections Severe Acute Respiratory Syndrome Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

45 Intermediate-size Expanded Access of Remestemcel-L, Ex-vivo Cultured Adult Human Mesenchymal Stromal Cells for Acute Respiratory Distress Syndrome Due to COVID-19 Infection

The objectives of this intermediate-size expanded access protocol are to assess the safety and efficacy of remestemcel-L in participants with ARDS due to coronavirus infection 2019 (COVID-19).

NCT04366830 Moderate to Severe Acute Respiratory Distress Syndrome Associated With COVID-19 Drug: Remestemcel-L

MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

46 Prevention and Treatment With Calcifediol of COVID-19 Coronavirus-induced Acute Respiratory Syndrome (SARS)

The administration of Calcifediol in patients with COVID-19, will reduce the development of SARS and the worsening of the various phases of the syndrome. Reducing at least 25% in ICU admission and death from the process, reducing days of hospitalization, facilitating the recovery of the same, acting significantly and positively, in any of its phases throughout the natural history of illness. As a treatment with extensive experience of clinical use, safe, inexpensive, and potentially very effective, it will have a highly efficient cost-benefit impact on the prevention of SARS.

NCT04366908 SARS-CoV 2 COVID19 SARS (Severe Acute Respiratory Syndrome) Cytokine Release Syndrome Cytokine Storm Drug: BAT + Calcifediol Drug: BAT

MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Syndrome

47 A Phase 3 Open-label, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Intravenously Administered Ravulizumab Compared With Best Supportive Care in Patients With COVID-19 Severe Pneumonia, Acute Lung Injury, or Acute Respiratory Distress Syndrome

This study will evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of ravulizumab administered in adult patients with Coronavirus Disease 2019 (COVID-19) severe pneumonia, acute lung injury, or acute respiratory distress syndrome. Patients will be randomly assigned to receive ravulizumab in addition to best supportive care (BSC) (2/3 of the patients) or BSC alone (1/3 of the patients). Best supportive care will consist of medical treatment and/or medical interventions per routine hospital practice.

NCT04369469 COVID-19 Severe Pneumonia Acute Lung Injury Acute Respiratory Distress Syndrome Pneumonia, Viral Biological: Ravulizumab Other: Best Supportive Care

MeSH:Pneumonia, Viral Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Lung Injury Syndrome

HPO:Pneumonia

48 Mesenchymal Stem Cells for the Treatment of Moderate to Severe COVID-19 Acute Respiratory Distress Syndrome

The mortality rate in SARS-CoV-2-related severe ARDS is high despite treatment with antivirals, glucocorticoids, immunoglobulins, and ventilation. Preclinical and clinical evidence indicate that MSCs migrate to the lung and respond to the pro-inflammatory lung environment by releasing anti-inflammatory factors reducing the proliferation of pro-inflammatory cytokines while modulating regulatory T cells and macrophages to promote resolution of inflammation. Therefore, MSCs may have the potential to increase survival in management of COVID-19 induced ARDS. The primary objective of this phase 3 trial is to evaluate the efficacy and safety of the addition of the mesenchymal stromal cell (MSC) remestemcel-L plus standard of care compared to placebo plus standard of care in patients with acute respiratory distress syndrome (ARDS) due to SARS-CoV-2. The secondary objective is to assess the impact of MSCs on inflammatory biomarkers.

NCT04371393 Mesenchymal Stromal Cells Remestemcel-L Acute Respiratory Distress Syndrome COVID Biological: Remestemcel-L Drug: Placebo

MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

49 Interventional Study to Evaluate the Efficacy of Therapeutic Plasma Exchange (TPE) Alone or in Combination With Ruxolitinib in COVID-19 Positive Patients With PENN Grade 2, 3, 4 Cytokine Released Syndrome (CRS)

This protocol will evaluate the efficacy of Therapeutic Plasma Exchange alone or in combination with ruxolitinib in COVID positive patients with PENN grade 2, 3, 4 cytokine release syndrome. It is hypothesized that dual intervention of acute apheretic depletion of cytokines and concomitant suppression of production will produce superior amelioration of the cytokine load and to help to prevent cytokine load rebound. This protocol is envisioned as a pilot study (n=20) for hypothesis generation for future investigation.

NCT04374149 Cytokine Release Syndrome COVID19 Procedure: Therapeutic Plasma Exchange Drug: Ruxolitinib

MeSH:Syndrome

50 Assessment of Extra Vascular Lung Water and Pulmonary Permeability by Transpulmonary Thermodilution in Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Acute respiratory distress syndrome (ARDS) is a syndromic definition of an acute lung injury with alteration of biomechanics (lower respiratory system compliance) mostly associated with increased lesional edema. Increase in Pulmonary Vascular Permeability Index (PVPI) accompanied with accumulation of excess Extravascular Lung Water (EVLW) is the hallmark of ARDS. In routine clinical practice, the investigators measure the EVLW and PVPI in ARDS patients, as suggested by expert's recommendations, using a transpulmonary thermodilution (TPTD) technique. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly recognized illness that has spread rapidly throughout Wuhan (Hubei province) to other provinces in China and around the world. Most critically ill patients with SARS-CoV-2 will present the criteria for the definition of ARDS. However, many of these patients have a particular form of ARDS with severe hypoxemia often associated with near normal respiratory system compliance. This combination is almost never seen in severe ARDS. Thus other mechanisms (including probably vascular mechanisms), that are still poorly described, have to be involved in SARS-CoV-2. EVLW and PVPI have never been assessed in SARS-CoV-2 mechanically ventilated patients. The aim of this study is to evaluate these two parameters in order to best characterize and understand the mechanisms related to SARS-CoV-2. Based on observation of several cases in intensive care units (ICU), the investigators hypothesize that there are following different SARS-CoV-2 patterns: 1. Nearly normal compliance, low lung recruitability, normal EVLW and low PVPI. 2. Low compliance due to increased edema, high lung recruitability, high EVLW and high PVPI.

NCT04376905 COVID-19 Pneumonia Acute Respiratory Distress Syndrome

MeSH:Pneumonia Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

HPO:Pneumonia

51 Comparison of the Efficacy and Safety of Tocilizumab Versus Methylprednisolone in the Cytokine Release Syndrome of Patients With COVID-19. A Prospective Randomized Controlled Phase II Trial

This study compare the efficacy and safety of tocilizumab versus methylprednisolone in the cytokine release syndrome of patients with COVID-19

NCT04377503 Cytokine Release Syndrome Covid-19 Drug: Tocilizumab 180 MG/ML Drug: Methylprednisolone Sodium Succinate

MeSH:Syndrome

52 A Study of Trans Crocetin in Patients With Acute Respiratory Distress Syndrome Due to COVID-19 Disease

This is an open label phase II study of treatment with LEAF-4L7520 and LEAF-4L6715 in patients who experience severe acute respiratory distress syndrome (ARDS) and are receiving artificial respiratory support due to COVID-19. The purpose of this study is to evaluate the improvement in PaO2/FiO2 by more than 25% in two cohorts of patients treated with LEAF-4L7520 or LEAF-4L6715.

NCT04378920 COVID19 Acute Respiratory Distress Syndrome Drug: LEAF-4L6715 Drug: LEAF-4L7520

MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

53 Effectiveness and Safety of Convalescent Plasma Therapy on COVID-19 Patients With Acute Respiratory Distress Syndrome in Referral Hospitals in Indonesia

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.

NCT04380935 COVID Acute Respiratory Distress Syndrome Biological: Convalescent plasma Drug: Standard of care

MeSH:Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Acute Lung Injury Syndrome

54 A Prospective, Randomized, Controlled Study Assessing Vagus Nerve Stimulation in CoViD-19 Respiratory Symptoms (SAVIORII)

The study is a prospective, randomized, controlled investigation designed for comparison of two groups for the reduction of respiratory distress in a CoViD-19 population, using gammaCore Sapphire (nVNS) plus standard of care (active) vs. standard of care alone (SoC), the control group. The gammaCore® (nVNS) treatments will be used acutely and prophylactically. The active and control groups will be diseased and severity matched. The primary objective is to reduce initiation of mechanical ventilation in patients with CoViD-19 compared to the control group. Secondary objectives are to evaluate cytokine trends/prevent cytokine storms, evaluate supplemental oxygen requirements, decrease mortality of CoViD-19 patients and to delay the onset of mechanical ventilation.

NCT04382391 COVID Corona Virus Infection Respiratory Failure Respiratory Distress Syndrome, Adult ARDS, Human SARS (Severe Acute Respiratory Syndrome) Device: gammaCore® Sapphire (non-invasive vagus nerve stimulator) Other: Standard of care therapies

MeSH:Severe Acute Respiratory Syndrome Coronavirus Infections Respiratory Distress Syndrome, Newborn Respiratory Distress Syndrome, Adult Respiratory Insufficiency Acute Lung Injury Syndrome Signs and Symptoms, Respiratory