Active clinical trials for "COVID-19"

The primary objective of the study is to evaluate the days until reaching clinical stability after starting randomization in hospitalized patients with elevated inflammatory parameters and severe COVID-19 lung injury.

This study aims to compare the efficacy and safety of Methylprednisolone versus Tocilizumab in improving clinical outcomes and reducing the need for ventilator support in COVID-19 patients with moderate COVID-19 disease at risk for complications of cytokine storm. Approximately 310 participants hospitalized with COVID-19 in UMMC, Hospital Sungai Buloh, Hospital Kuala Lumpur and Hospital Tuanku Jaafar will be enrolled into this study. Eligible participants will be selected based on a set of clinical, laboratory and radiological parameters indicative of early stages of CRS and lung function decline prior to being randomized at a ratio of 1:1 to receive either Tocilizumab or Methylprednisolone. Participants will be monitored daily for clinical and laboratory parameters, and at 48 hours, switched to the alternate study arm should they manifest signs and symptoms indicative of decompensation.

Title: The use of Tocilizumab in the management of patients who have severe COVID-19 with suspected pulmonary hyperinflammation. This is a study designed to assess the therapeutic value of intravenous tocilizumab administered as single 8mg/Kg dose in patients affected by SARS-CoV2 infection with a pulmonary manifestation causing hypoxia. Aim of the study is to test the hypothesis that anti-IL6 treatment can be effective in reducing the virus-induced cytokine storm, blocking deterioration of lung function or even promoting a rapid improvement of clinical conditions, preventing tracheal intubation and/or death. This drug will be administered to those patients entering the ICU with severe acute respiratory failure COVID-19 disease. The endpoints are death and duration of hospitalization. The patients will be assessed with surrogate markers determining the level of the cytokine storm.

Combination of Recombinant Bacterial ACE2 receptors -like enzyme of B38-CAP and Isotretinoin could be promising treatment for COVID-19 infection- and Its inflammatory complications Mahmoud ELkazzaz1 1Department of chemistry and biochemistry, Faculty of Science, Damietta University, Egypt. _____________________________________________________________________________________________________________________________________________________________________ B38-CAP is a bacteria-derived ACE2-like enzyme that suppresses hypertension and cardiac dysfunction Angiotensin-converting enzyme 2 (ACE2) is critically involved in cardiovascular physiology and pathology, and is currently clinically evaluated to treat acute lung failure. Here we show that the B38-CAP, a carboxypeptidase derived from Paenibacillus sp. B38, is an ACE2-like enzyme to decrease angiotensin II levels in mice. In protein 3D structure analysis, B38-CAP homolog shares structural similarity to mammalian ACE2 with low sequence identity. A study demonstrated that the bacterial B38-CAP as an ACE2-like carboxypeptidase, indicating that evolution has shaped a bacterial carboxypeptidase to a human ACE2-like enzyme. Bacterial engineering could be utilized to design improved protein drugs for hypertension and heart failure. pretreatment of B38-CAP markedly down regulated a massive increase of plasma Ang II levels at 5 min after Ang II injection In addition to the currently used drugs to inhibit Ang II generation or signaling, such as ACE inhibitors or Angiotensin receptor blockers, direct down-modulation of Ang II levels by rhACE2 protein is one of the promising candidates for new therapeutic strategy in cardiovascular disease and other Ang II-related diseases, e.g. ARDS. On the other hand, although mass production of rhACE2 as a protein drug costs due to requirement of mammalian cell expression systems, B38-CAP is easily prepared with E. coli expression system and is cost effective. Therapeutic efficacy and less toxicity in mouse heart failure models would warrant further investigation of B38-CAP or other microbial carboxypeptidases in disease models. Finally the principal investigator expects that treatment with ACE2-like enzyme of bacteria B38-CAP expected to work efficiently Like human ACE2 and it will save the lung cells from COVID - 19 inhibitory effect and down regulation of ACE2 because COVID-19 binds to human ACE2 and down regulates it and this receptors is very important for lung cells survival and function So ,the principal investigator also expects that B38-CAP ACE2 like enzyme may be not recognized by COVID -19 spike protein because evolutionary it is too far away from human ace2 and human ACE2 is a real receptor of COVID -19 not ACE2 like enzyme but in the same time it will make the same function of human ACE2 In another study by Sinha et al who analyzed a publicly available Connectivity Map (CMAP) dataset of pre/post transcriptomic profiles for drug treatment in cell lines for over 20,000 small molecules, isotretinoin was the strongest down-regulator of ACE 2 receptors. On the other hand, they found 6 drugs in CMAP that are currently being investigated in clinical trials for treating COVID-19 (chloroquine, thalidomide, methylprednisolone, losartan, lopinavir and ritonavir, from clinicaltrials.gov), none of which was found to significantly alter ACE2 expression (P>0.1) Moreover, another study demonstrated that isotretinoin is a Potential papain like protease (PLpro) inhibitors which is a protein encoded by SARS-CoV-2 genes and considered one of the proteins that should be targeted in COVID-19 treatment by performing target-based virtual ligand screening . So, the principal investigator expects strong inhibition of COVID - 19 infection And rescuing the lung cells from its serious attack by treating with ACE2 like enzyme and Isotretinoin Keywords: COVID 2019 , Isotretinoin,B38-CAP , Bacterial ACE2 receptors -like enzyme , rhACE226.

The novel coronavirus disease (COVID-19), which began in Wuhan, China, in December 2019, has been declared to be a pandemic by the World Health Organization (WHO), Caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), COVID-19 has resulted in 1,781,127 cases and 108,994 deaths globally (till 12th April, 2020), affecting 199 countries and 2 international conveyances. US FDA has recently approved Convalescent Plasma from patients recovered from COVID 19 for the treatment of severe or life threatening COVID-19 infections. In a small case series, five critically ill COVID-19 patients with ARDS were treated with convalescent plasma containing neutralizing antibodies. Infusion of plasma was followed by improvement in clinical status in all five patients, with no deaths and the study reported that three patients were discharged, whilst two continued to be stable on mechanical ventilation. We designed this phase II, open label, randomized clinical trial with the primary objective to assess the safety and efficacy of the therapy in the second stage.

COVID-19 Infection has been found to cause endothelial dysfunction and most of the adverse events stem to this mechanism. So we seek to target endothelial dysfunction in critically Ill patients with covid by giving them an endothelial protocol ( L-arginine, Folic Acid, Statin, Nicorandil, Vitamin B complex) and monitor clinical outcome in those patients.

Inflammatory diseases favour the onset of venous thromboembolic events in hospitalized patients. Thromboprophylaxis with a fixed dose of heparin/low molecular weight heparin (LMWH) is recommended if concomitant inflammatory disease. In severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) pneumonia an inflammation-dependent thrombotic process occurs and platelet activation may promote thrombosis and amplify inflammation, as indicated by previous experimental evidence, and the similarities with atherothrombosis and thrombotic microangiopathies. Antiplatelet agents represent the cornerstone in the prevention and treatment of atherosclerotic arterial thromboembolism, with limited efficacy in the context of venous thromboembolism. The use of acetylsalicylic acid may improve inflammation and respiratory function in humans as indicated by the results of observational studies. There are no validated protocols for thrombosis prevention in Covid-19. There is scientific rationale to consider acetylsalicylic acid for the prevention of thrombosis in the pulmonary circulation and attenuation of inflammation. This is supported by numerous demonstrations of the anti-inflammatory activity of antiplatelet agents and the evidence of improvement in respiratory function both in human and experimental pathology. The hypothesis underlying the present study project is that in Covid-19 platelet activation occurs through an inflammation-dependent mechanism and that early antithrombotic prophylaxis in non-critical patients could reduce the incidence of pulmonary thrombosis and respiratory and multi-organ failure improving clinical outcome in patients with SARS-CoV2 pneumonia. The prevention of thrombogenic platelet activity with acetylsalicylic acid could be superior to fixed dose enoxaparin alone. The proposed treatment is feasible in all coronavirus disease 2019 (COVID-19) patients, regardless of the treatment regimen (antivirals, anti-inflammatory drugs), except for specific contraindications. To this aim, the investigators a randomised, placebo-controlled, double blind, parallel arms study to investigate the potential protection of acetylsalicylic acid towards the progression of lung failure in patients admitted to a medical ward for SARS-CoV-2 pneumonia. A 15-day treatment period is considered. Primary endpoint is the occurrence of one of the following events: admission to an intensive care unit, requirement of mechanical ventilation, PaO2/FiO2 less than 150 mm Hg.

Acute myocardial injury has been a finding of variable frequency among patients diagnosed with COVID-19. It is now recognized that cTnI levels are strongly associated with increased mortality. The mechanisms underlying the myocardial injury remain unknown, and it is not clear whether they reflect local/systemic inflammatory process and/or cellular ischemia. Both myocardial ischemia and ventricular dysfunction result in dramatic changes in mitochondrial oxidative metabolism. These changes involve an increase in the rate of cytoplasmic anaerobic glycolysis to compensate for the decrease in mitochondrial adenosine triphosphate (ATP) production. The rest of the mitochondrial oxidative metabolism originates mainly from the β-oxidation of free fatty acids, which occurs at the expense of glucose oxidation. Trimetazidine is a competitive inhibitor of the enzyme 3-ketoacyl coenzyme A (CoA) long-chain thiolase (3-KAT), the last enzyme involved in the oxidation of fatty acids. Stimulation of glucose oxidation by trimetazidine results in a better coupling between glycolysis and glucose oxidation, with a consequent decrease in lactate production and intracellular acidosis, present in situations of myocardial ischemia or heart failure. Thus, the PREMIER-COVID-19 study was designed to test the hypothesis that the use of trimetazidine associated with usual therapy in patients admitted with a diagnosis of moderate to severe acute respiratory syndrome by SARS-CoV2 infection reduces the extent of acute myocardial injury assessed by the peak release of ultra-sensitive troponin compared to usual therapy.

This is an open-label Phase I study, four dose escalation groups, to evaluate the safety of CD24-exosomes in patients with moderate/severe COVID-19 disease. Patients with moderate/severe COVID-19 infection and factors predictive of a cytokine storm are recruited from the Corona department of the Tel Aviv Sourasky Medical Center (TASMC), who have provided informed consent are being recruited in four dose groups who will receive the exosome treatment as an add-on treatment to standard treatment.

Coronavirus 19 (COVID-19) is a viral respiratory disease that was identified in December 2019 after the first cases in China, spreading rapidly until reaching pandemic status, causing the collapse of numerous health systems and strong economic and social impact. By the end of April 2020, 3.08 million cases, and more than 214 thousand deaths were already recorded. The treatment so far has not been established and there are several clinical trials testing known drugs that have antiviral activity in vitro, due to the urgency that the global situation imposes. Medicines with specific actions can take years to be discovered, while a vaccine also takes a long time. Recently, it has been shown that the worsening of Coronavirus infection may be related to the formation of micro clots in blood vessels and anticoagulants have been used as adjuvants in the treatment. This study is justified by conducting a pilot study that showed an in vitro antiviral action (anti-COVID-19) of high molecular weight heparin. Methods: A phase I / II clinical trial will be conducted. 40 participants will be included in two arms. Participants allocated to Group 1 (control) will receive inhalation with 0.9% saline applied 4/4 hours, for 7 days. Participants allocated to Group 2 (intervention) will receive high molecular weight inhaled heparin (250ug / mL 0.9% SF), at a 4/4 hour dose, for 7 days. The outcomes of interest will be safety (absence of moderate or serious adverse events) and effectiveness (measured in a score of 7 points, with 1 absence of limitations and 7, death). Expected results: The development of a new therapeutic option for COVID-19 is expected, with the possibility of use in other serious coronavirus diseases, to be subsequently tested in phase III studies.