Name (Synonyms) | Correlation | |
---|---|---|
drug802 | Mavrilimumab Wiki | 0.43 |
drug1622 | oxyhydrogen Wiki | 0.30 |
drug957 | Oxygen Wiki | 0.30 |
drug666 | Immunological profiling Wiki | 0.30 |
drug1309 | Stem Cell Educator-Treated Mononuclear Cells Apheresis Wiki | 0.30 |
drug783 | MSC Wiki | 0.30 |
drug424 | Dexmedetomidine Injectable Product Wiki | 0.30 |
drug75 | Anakinra alone (stages 2b/3) Wiki | 0.30 |
drug76 | Anakinra and Ruxolitinib (overcome stage 3) Wiki | 0.30 |
drug30 | ABX464 Wiki | 0.30 |
drug335 | Colchicine Wiki | 0.12 |
drug1285 | Standard of care Wiki | 0.08 |
drug1042 | Placebos Wiki | 0.08 |
drug1035 | Placebo oral tablet Wiki | 0.06 |
drug129 | Azithromycin Wiki | 0.06 |
drug1016 | Placebo Wiki | 0.05 |
drug591 | Hydroxychloroquine Wiki | 0.03 |
Name (Synonyms) | Correlation | |
---|---|---|
D015817 | Eye Infections NIH | 0.30 |
D000071257 | Emergence Delirium NIH | 0.30 |
D003231 | Conjunctivitis NIH | 0.21 |
D003693 | Delirium NIH | 0.21 |
D013577 | Syndrome NIH | 0.08 |
D011014 | Pneumonia NIH | 0.06 |
D012128 | Respiratory Distress Syndrome, Adult NIH | 0.06 |
D011024 | Pneumonia, Viral NIH | 0.04 |
D014777 | Virus Diseases NIH | 0.04 |
D055371 | Acute Lung Injury NIH | 0.04 |
D012127 | Respiratory Distress Syndrome, Newborn NIH | 0.04 |
D045169 | Severe Acute Respiratory Syndrome NIH | 0.02 |
D018352 | Coronavirus Infections NIH | 0.01 |
Name (Synonyms) | Correlation | |
---|---|---|
HP:0000509 | Conjunctivitis HPO | 0.21 |
HP:0002090 | Pneumonia HPO | 0.07 |
There are 11 clinical trials
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.
Description: The feasibility will be evaluated by the number of Covid-19 patients who were unable to complete SCE Therapy.
Measure: Determine the number of Covid-19 patients who were unable to complete SCE Therapy Time: 4 weeksDescription: Measurements of immune markers' changes will be preformed by flow cytometry such as activated T cells. Peripheral blood mononuclear cells (PBMC) will be collected at 1, 3, 6, 9, 12, 28 day post the SCE therapy.
Measure: Examine the percentage of activated T cells after SCE therapy by flow cytometry Time: 4 weeksDescription: Measurements of immune marker's changes will be preformed by flow cytometry such as the percentage of Th17 cells. Peripheral blood mononuclear cells (PBMC) will be collected at 1, 3, 6, 9, 12, 28 day post the SCE therapy.
Measure: Assess the percentage of Th17 cells after SCE therapy by flow cytometry Time: 4 weeksDescription: Patients will be monitored for their chest imaging every 3 - 5 days for 4 weeks after receiving SCE therapy.
Measure: Chest imaging changes by computed tomography (CT) scan of the chest Time: 4 weeksDescription: To determine the viral load by real time RT-PCR, samples of blood, sputum, nose / throat swab will be collected from patients during the follow-up studies after receiving SCE therapy.
Measure: Quantification of the SARS-CoV-2 viral load by real time RT-PCR Time: 4 weeksThe aim of the present study is to examine the inflammatory response in the pulmonary compartment and blood of critically ill patients admitted to the ICU with COVID-19.
Description: Total white blood cells, neutrocytes, lymphocytes, and monocytes in bronchoalveolar lavage fluid and blood
Measure: White blood cell counts Time: Day 0 (subsequent to study inclusion in the ICU)Description: Total white blood cells, neutrocytes, lymphocytes, and monocytes in bronchoalveolar lavage fluid and blood
Measure: White blood cell counts Time: Day 7Description: Cell populations and subpopulations evaluated by 10 colored flow cytometry (B cells, T cells, TCR subsets, Tregs/Th17, dendritic cells, myeloid cells and neutrophils) in bronchoalveolar lavage fluid and blood
Measure: Lymphocyte populations Time: Day 0 (subsequent to study inclusion in the ICU)Description: Cell populations and subpopulations evaluated by 10 colored flow cytometry (B cells, T cells, TCR subsets, Tregs/Th17, dendritic cells, myeloid cells and neutrophils) in bronchoalveolar lavage fluid and blood
Measure: Lymphocyte populations Time: Day 7Description: Multiplex assay for measuring cytokines in bronchoalveolar lavage fluid and plasma (e.g. IL-1-beta, IL-1RA, IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-33, IL-35, TGF-beta, TNF-alpha, HMGB1)
Measure: Cytokines Time: Day 0 (subsequent to study inclusion in the ICU)Description: Multiplex assay for measuring cytokines in bronchoalveolar lavage fluid and plasma (e.g. IL-1-beta, IL-1RA, IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-33, IL-35, TGF-beta, TNF-alpha, HMGB1)
Measure: Cytokines Time: Day 7Description: MBL, ficolin-1, ficolin-2, ficolin-3, and MASPs in bronchoalveolar lavage fluid and plasma
Measure: Lectin complement pathway Time: Day 0 (subsequent to study inclusion in the ICU)Description: MBL, ficolin-1, ficolin-2, ficolin-3, and MASPs in bronchoalveolar lavage fluid and plasma
Measure: Lectin complement pathway Time: Day 7Description: Growth of pathogenic microorganisms in body fluids (e.g. urine, blood, bronchoalveolar lavage fluid)
Measure: Microorganisms Time: Up to 12 weeksDescription: Respiratory filmarray PCR for testing for pathogens
Measure: Respiratory pathogens Time: Day 0 (subsequent to study inclusion in the ICU)Description: Respiratory filmarray PCR for testing for pathogens
Measure: Respiratory pathogens Time: Day 7Description: 16S ribosomal RNA (rRNA) and 18S rRNA PCR for bacterial or fungal pathogen identification in bronchoalveolar lavage fluid
Measure: Ribosomal RNA in the airways Time: Day 0 (subsequent to study inclusion in the ICU)Description: 16S ribosomal RNA (rRNA) and 18S rRNA PCR for bacterial or fungal pathogen identification in bronchoalveolar lavage fluid
Measure: Ribosomal RNA in the airways Time: Day 7Description: Semiquant PCR of SARS-CoV-2 in bronchoalveolar lavage fluid
Measure: Levels of SARS-CoV-2 in the airways Time: Day 0 (subsequent to study inclusion in the ICU)Description: Semiquant PCR of SARS-CoV-2 in bronchoalveolar lavage fluid
Measure: Levels of SARS-CoV-2 in the airways Time: Day 7Description: ICU mortality
Measure: Mortality Time: Up to 6 monthsDescription: In hospital mortality
Measure: Mortality II Time: Up to 6 monthsDescription: C-reactive protein, procalcitonin, ferritin
Measure: Blood markers of inflammation Time: Daily assessment in the ICU up to 12 weeksDescription: Platelets, creatinine, urea, sodium, potassium, D-dimer, lactate dehydrogenase, bilirubin, lactate
Measure: Blood markers of organ dysfunction Time: Daily assessment in the ICU up to 12 weeksDescription: Number of participants with unilateral infiltrates or bilateral infiltrates and/or air bronchogram
Measure: Infiltrates on conventional chest x-ray Time: Up to 12 weeksA 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
Description: (Presence/Absence) requirement of mechanical ventilation
Measure: Mechanical ventilation Time: expected within first three days (non conclusive due to lack of evidence yet)Description: Duration of mechanical ventilation if it is required (hours from the start)
Measure: Duration of mechanical ventilation Time: expected within first seven days (non conclusive due to lack of evidence yet)Description: Delirium criteria as defined in DSM-4
Measure: Delirium on recovery from sedation Time: First 24 hours after retiring dexmedetomidine sedationDuring SARS-Cov2 infection with serious respiratory implication and high systemic inflammation level, intravenous ANAKINRA alone or associated with RUXOLITINIB for severe cases might reduce inappropriate systemic inflammatory response, improve breathing and decrease occurrence or duration of ARDS and associated mortality.
Description: At least 3 parameters are met including CRP and/or Ferritin among: CRP: decrease > 50% Ferritinemia: decrease > 1/3 Serum creatinine: decrease > 1/3 AST/ALT: decrease > 50% Eosinophils > 50 /mm3 Lymphocytes > 1000 /mm3
Measure: Biological criteria Time: 7 days from enrolmentDescription: Number of days without mechanical ventilation
Measure: Duration of oxygen therapy (days) Time: 28 days from enrolmentDescription: Number of patients included in stage 2b
Measure: Number of intensive care units admissions Time: 28 days from enrolmentDescription: Number of days in intensive care units for patients managed in intensive care units
Measure: Number of days in intensive care units Time: 28 days from enrolmentDescription: Mortality rate
Measure: Mortality rate Time: 28 days from enrolmentDescription: Total number of days in hospital
Measure: Total number of days in hospital Time: 28 days from enrolmentDescription: Organ failure score modification (Sepsis-related Organ Failure Assessment (SOFA) score); Sofa score's minimum and maximum values are 0 and 24, the lowest score corresponds to a better outcome.
Measure: Organ failure score modification (Sepsis-related Organ Failure Assessment (SOFA) score) Time: 28 days from enrolmentDescription: Number of bacterial and/or fungal sepsis
Measure: Number of bacterial and/or fungal sepsis Time: 28 days from enrolmentThe world is currently facing a pandemic due to the outbreak of a new coronavirus causing acute respiratory failure called SARS-Cov2. The majority of patients (8 out of 10) are known to have mild disease, manifested by respiratory tract symptoms associated with fever, headache, and body pain. However, it is possible that the disease progresses to a severe stage, whith the need for mechanical ventilation support associated with high morbidity and mortality. The progression of the disease is mainly due to the appearance of uncontrolled inflammation that also favors the development of disseminated clots. So far, there is no effective treatment to combat coronavirus; however, the use of anti-inflammatory drugs is potentially effective in preventing complications from the disease. In this regard, low dose colchicine is relatively safe and effective as an anti-inflammatory. It has been used for many years in the control of inflammation secondary to the accumulation of uric acid crystals. The aim of this study is to test if the administration of colchicine at a dose of 1.5 mg the first day and subsequently 0.5 mg BID until completing 10 days of treatment is effective as a treatment for inflammation related symptoms in patients with mild and severe disease secondary to coronavirus infection. The primary outcome is improvement of symptoms related to inflammation and avoiding progression to severe and critical stages of the disease. Colchicine can be discontinued before the end of 10 days in case of serious adverse effects or if the patient progresses to the critical stages of the disease.
Description: Resolution of fever, myalgia and arthralgia and 50% improvement of total lymphocyte count, D-dimer, fibrinogen and ferritin
Measure: Number of patients with improvement in body temperature, myalgia, arthralgia, total lymphocyte count, D-dimer, fibrinogen and ferritin levels Time: Up to 24 daysDescription: At least one of the following: respiratory failure, respiratory rate > 30 rpm, oxygen saturation < 92%, PaO2/FiO2 < 300 mmHg
Measure: Progression to severe disease Time: Up to 10 daysSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a newly identified, highly contagious RNA virus causing respiratory infectious disease, Coronavirus Disease 2019 (COVID-19). Conjunctivitis has been reported as a rare finding of the disease, and preliminary studies showed that the virus RNA could be detected in ocular secretions using polymerase chain reaction (PCR) assays when conjunctivitis present. This study aims to estimate the proportion of SARS-CoV-2 associated conjunctivitis among patients with suspected viral conjunctivitis presented to the ophthalmology clinics of Wilmer Eye Institute during the COVID-19 pandemic. The investigators also aim to identify whether SARS-CoV-2 associated conjunctivitis is an isolated finding or an early sign of COVID-19.
Description: Number of conjunctival samples with positive PCR divided by the total number of conjunctival samples
Measure: Proportion of conjunctival samples tested positive for SARS-CoV-2 Time: 1 yearDescription: Number of nasal samples with positive PCR divided by the number of conjunctival samples with positive PCR
Measure: Proportion of nasal samples tested positive for SARS-CoV-2 among patients with positive conjunctival samples Time: 1 yearDescription: Number of nasopharyngeal samples with positive PCR divided by the number of conjunctival samples with positive PCR
Measure: Proportion of nasopharyngeal samples tested positive for SARS-CoV-2 among patients with positive conjunctival samples Time: 1 yearDescription: Number of patients developed COVID-19 divided by the number of the study population
Measure: Rate of development of COVID-19 in the study patient population Time: 1 yearDescription: Number of conjunctival samples with positive PCR divided by the number of patients developed COVID-19
Measure: Positive conjunctival sample rate in patient developed COVID-19 Time: 1 yearTo evaluate the safety, toxicity and immunological effects of infusion of allogeneic bone marrow-derived human mesenchymal stem (stromal) cells (MSCs) and whether this therapy has an influence on the resolution processes in ARDS patients infected with Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Description: improvement of lung injury score (LIS), 0-16 points, severity increasing with higher points
Measure: lung injury score Time: day 10Description: D-dimers blood levels
Measure: D-dimers Time: day 0, 1, 2, 3, 10 and 15Description: distribution of phenotypes of immune cells
Measure: phenotype Time: day 0, 1, 2, 3, 10 and 15Description: Levels of specialized pro-resolving lipid mediators within alveolar macrophages and bronchoalveolar lavage
Measure: pro-resolving lipid mediators Time: day 0, 1, 2, 3, 10 and 15Description: Cytokine concentration within bronchoalveolar lavage and Serum prior and after MSC infusions
Measure: cytokines Time: day 0, 1, 2, 3, 10 and 15Description: Chemokine concentration within bronchoalveolar lavage and Serum prior and after MSC infusions
Measure: chemokines Time: day 0, 1, 2, 3, 10 and 15Description: Survival at 10 days and 28 days
Measure: Survival Time: day 10 and 28Description: Time to removal of endotracheal tube
Measure: extubation Time: day 28Description: lymphocyte subpopulations in peripheral blood by flow cytometry prior and after MSC infusion (day 0,3,5,10)
Measure: lymphocyte subpopulations Time: day 0, 3, 5 and 10Description: evaluate SARS-CoV-2-specific antibody titers in the serum of patients prior and post MSC infusion.
Measure: SARS-CoV-2-specific antibody titers Time: day 0, 5 and 10Description: evaluate levels of complement molecules (C5-C9) in the serum of patients prior and post MSC infusion
Measure: complement molecules (C5-C9) Time: day 0, 5 and 10A phase 2/3, randomized, double blind, placebo-controlled study to evaluate the efficacy and the safety of ABX464 in treating inflammation and preventing acute respiratory failure in patients aged ≥65 and patients aged ≥18 with at least one additional risk factor who are infected with SARS-CoV-2 (the MiR-AGE study).
Description: 7-point ordinal scale is defined as Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death
Measure: Percentage of patients reporting each severity rating on a 7-point ordinal scale Time: 28-day treatment periodDescription: Nasopharyngeal sample and/or in blood
Measure: SARS-CoV-2 viral load Time: at each study visit during the 28-day treatment periodThis study is a prospective, phase II, multi-center, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of mavrilimumab in hospitalized patients with acute respiratory failure requiring oxygen supplementation in COVID- 19 pneumonia and a hyper-inflammatory status. The study will randomize patients to mavrilimumab or placebo, in addition to standard of care per local practice. The total trial duration will be 12 weeks after single mavrilimumab or placebo dose.
Description: Time to the absence of need for oxygen supplementation (time to first period of 24 hrs with a SpO2 of 94%) within day 14 of treatment, stated as Kaplan- Mayer estimates of the proportion of patients on room air at day 14 and median time to room air attainment in each arm
Measure: Reduction in the dependency on oxygen supplementation Time: within day 14 of treatmentDescription: Response is defined as a 7-point ordinal scale of 3 or less, i.e. no supplemental oxygen
Measure: Proportion of responders (using the WHO 7-point ordinal scale) Time: Day 7, 14, and 28Description: Time from date of randomization to the date with a 7-point ordinal scale of 3 or less, i.e. no supplemental oxygen
Measure: Time to response (using the WHO 7-point ordinal scale) Time: Within day 28 of interventionDescription: Proportion of patients with at least two-point improvement in clinical status
Measure: Proportion of improving patients (using the WHO 7-point ordinal scale) Time: At day 7, 14, and 28Description: Time to resolution of fever (for at least 48 hours) in absence of antipyretics, or discharge, whichever is sooner
Measure: Time to resolution of fever Time: Within day 28 of interventionDescription: COVID-19-related death
Measure: Reduction in case fatality Time: Within day 28 of interventionDescription: Proportion of hospitalized patients who died or required mechanical ventilation (WHO Categories 6 or 7)
Measure: Proportion of patient requiring mechanical ventilation/deaths Time: Within day 14 of interventionDescription: Change of the following serological markers over follow-up (C-reactive protein; Ferritin; D-Dimer)
Measure: Change in biochemical markers Time: Within day 28 of intervention or discharge -whatever comes firstDescription: Median changes of NEWS2 score from baseline
Measure: Median changes in the National Early Warning Score 2 (NEWS2) Time: At day 7, 14, and 28Description: Time to clinical improvement (as defined as a NEWS2 score of 2 or less maintained for at least 24 hours or discharge, whichever comes first)
Measure: Time to clinical improvement as evaluated with the National Early Warning Score 2 (NEWS2) Time: Within day 28 of intervention or discharge -whatever comes firstDescription: Variations from baseline to subsequent timepoints (when available) in terms of percentage of lung involvement, modifications in the normal parenchyma, ground glass opacities (GGO), crazy paving pattern,parenchymal consolidations, and evolution towards fibrosis.
Measure: Variations in radiological findings Time: Within day 28 of intervention or discharge -whatever comes firstDescription: Number of patients with treatment- related side effects (as assessed by Common Terminology Criteria for Adverse Event (CTCAE) v.5.0), serious adverse events, adverse events of special interest, clinically significant changes in laboratory measurements and vital signs
Measure: Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] Time: By day 84Description: To evaluate the primary and secondary endpoints in different subgroups of patients: mild respiratory failure: PaO2/FiO2 ≤ 300 and > 200 mmHg; moderate respiratory failure: PaO2/FiO2 ≤ 200 and > 100 mmHg
Measure: Clinical efficacy of mavrilimumab compared to the control arm by clinical severity Time: Within day 28 of interventionDescription: Median changes in serum IL-6
Measure: Changes in serum IL-6 (exploratory biomarker) Time: By day 84Description: Median changes in serum IL-1 receptor antagonist
Measure: Changes in serum IL-1RA (exploratory biomarker) Time: By day 84Description: Median changes in serum TNF-alpha
Measure: Changes in serum TNF-alpha (exploratory biomarker) Time: By day 84Description: Median variations in haemoglobin and leucocyte counts
Measure: Changes in CBC + differential (exploratory biomarker) Time: By day 84Description: Median titres od anti-SARS-CoV2 antibodies
Measure: Level of anti-SARS-CoV2 antibodies (exploratory biomarker) Time: By day 84Description: Proportion of patients with a positive swab for SARS-CoV2 by PCR
Measure: Virus eradication (exploratory biomarker) Time: By day 84Description: Proportion of patients who developed anti-drug antibodies
Measure: Anti-drug antibodies (exploratory biomarker) Time: By day 84The purpose of this prospective, Phase 2, multicenter, blinded, randomized placebo controlled study is to demonstrate that early treatment with mavrilimumab prevents progression of respiratory failure in patients with severe COVID-19 pneumonia and clinical and biological features of hyper-inflammation.
Description: Number of subjects alive and off of oxygen
Measure: Proportion of subjects alive and off of oxygen at day 14 Time: Day 14Description: Number of subjects alive and without respiratory failure
Measure: Proportion of subjects alive and without respiratory failure at 28 days Time: Day 28COVID-19 is a rapidly evolving pandemic with approximately 5% of all patients which require intensive care unit admission. In critically ill patients infected with COVID-19, approximately 15% had severe shock requiring medications to increase blood pressure. It appears that blood vessel tone is altered and microcirculation is not well regulated in patients with COVID-19. The underlying pathophysiology and contributing factors are unknown. The association with subsequent organ dysfunction and outcome is also unclear. Therefore, we aim to investigate serial changes of relevant biomarkers in this population to improve the understanding of this disease, to investigate the association with clinically important outcomes and to find out how best to treat patients. The data will serve to develop strategies for individualised management of this high-risk group.
Description: Plasma bio-adrenomedullin, proenkephalin, dipeptidyl peptidase-3, renin and angiotensin II
Measure: Plasma bio-adrenomedullin, proenkephalin, dipeptidyl peptidase-3, renin and angiotensin II Time: Daily from admission, and around the onset of vasodilatory shock until day 7Description: Duration of vasodilatory shock
Measure: Duration of vasodilatory shock Time: 7 and 28 daysDescription: As defined by the Kidney Disease: Improving Global Outcomes criteria
Measure: Acute kidney injury Time: 7 and 28 daysDescription: Need for renal replacement therapy
Measure: Need for renal replacement therapy Time: 7 and 28 daysDescription: Duration of ventilation
Measure: Duration of ventilation Time: 7 and 28 daysDescription: Duration of extracorporeal membrane oxygenation
Measure: Duration of extracorporeal membrane oxygenation Time: 7 and 28 daysDescription: ICU and hospital
Measure: Mortality Time: 28 days