Based on data regarding the effect of colchicine on the inflammasome NLP3 and microtubule formation and associations thereof with the pathogenetic cycle of SARS-COV-2, the question arises whether colchicine, administered in a relatively low dose, could potentially have an effect the patients' clinical course by limiting the myocardial necrosis and pneumonia development in the context of COVID-19. If present, this effect would be attributed to its potential to inhibit inflammasome and (less probably) to the process of SARS-CoV-2 endocytosis in myocardial and endothelial respiratory cells.

NCT04326790

Conditions

1. Corona Virus Disease 19 (Covid 19)

Interventions

1. Drug: Colchicine
2. Drug: Standard treatment

MeSH:Virus Diseases

Submitted by Mahmoud Elkazzaz Assessment the Activity Value of 13- cis-Retinoic Acid(Isotretinoin) in the Treatment of COVID-19 Mahmoud ELkazzaz(1),Tamer Haydara(2), Mohamed Abdelaal(3), Ahmed M. Kabel(4), Abedelaziz Elsayed(5) ,Yousry Abo-amer(6) ,Hesham Attia(7) 1. Department of chemistry and biochemistry, Faculty of Science, Damietta University,GOEIC,Egypt. 2. Department of Internal Medicine,Faculty of Medicine, Kafrelsheikh University, Egypt 3. Department of Cardiothoracic Surgery,Faculty of Medicine, Kafrelsheikh University, Egypt 4. Department of Clinical Pharmacy, Faculty of Medicine , Tanta University,Egypt. 5. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy,Tanta University,Egypt. 6. Hepatology,Gastroenterology and Infectious Diseases Department, Mahala Hepatology Teaching Hospital,Egypt 7. Department of Immunology and Parasitology, Faculty of Science, Cairo University, Egypt. - Study Chair ((( Dr.Tamer Hydara))), Department of Internal Medicine,Faculty of Medicine, Kafrelsheikh University, Egypt - Contact: Dr.Tamer Hydara-Tel: 00201142233340 Mail: tamerhydara@yahoo.com - Principal Investigator (((Mahmoud Elkazzaz))), Faculty of Science, Damietta University,GOEIC,Egypt. - Contact:Tel: 00201090302015 Mail: mahmoudramadan2051@yahoo.com - Study coordinator ((Prof/Dr Mohamed Abdelaal)), Department of Cardiothoracic Surgery,Faculty of Medicine, Kafrelsheikh University, Egypt - Contact:Tel: 00201001422577 Mail: Malaal2@hotmail.com Abstract The COVID-19 pandemic caused by SARS-COV-2 has infected over 2,000,000 people causing over 150,000 deaths. Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 and for which there are currently no approved treatments. Here, the principal investigator reported according to previous studies and research findings that Isotretinoin can strongly affect both inflammation and viral entry in severe acute respiratory syndrome coronavirus 2 infection via inhibiting the overproduction of early response proinflammatory cytokines (IL- 6 and tumor necrosis factors alpha ) which are over expressed in COVID-19 and contributed to disease progression, poor outcomes, vascular hyperpermeability and multiorgan failure in patients infected with severe acute respiratory syndrome(SARS-CoV-2) and also, via blocking COVID-19 entry by inhibiting androgenic factors which induce transmembrane protease, serine 2 (TMPRSS2) expression, In addition to inhibiting of Angiotensin-converting enzyme 2(ACE2) ,AT1 protein and Ang II-mediated intracellular calcium release pathway which is responsible for SARS-CoV-2 cell fusion and entry as opposed to ACE inhibitors (ACEIs) or angiotensin II type-I receptor blockers (ARBs) that upregulate ACE-2 receptors which might increase the risk of infection and subsequent complications Moreover, another study demonstrated that isotretinoin is a potential inhibitor of papain like protease (PLpro) which is a protein expressed by SARS-CoV-2 RNA and considered one of the proteins that should be targeted in COVID-19 treatment. And also,more than one study reported that 13 cis Retinoic Acid induces CD4+CD25+FOXP3+ Regulatory T Cells which their absence during acute infection alters the ability of the host to limit tissue damage In addition, isotretinoin was reported to increase CD4 counts and markedly decrease viremia in HIV positive patients suffering from acne vulgaris and retinoic acid inducible gene-1 (RIG-1) expression. And also, another study reported that 13 Cis retinoic acid induced significant upregulation of toll-like receptor 3 resulting in an immune response to dsRNA intermediate which can be partially generated during CoV-2 replication . TLR3 sensitized by dsRNA and cascades of signaling pathways (IRFs and NFκB activation, respectively) are activated to produce type I IFNs. The production of type I IFNs is important to enhance the release of antiviral proteins for the protection of uninfected cells. Isotretinoin therapy has furthermore proven anti-inflammatory, anti-platelet and fibrinolytic activities. which may protect patients infected with covid-19 from widespread blood clots. From this point, the principal investigator expects that isotretinoin will be the Immunity passport" in the context of COVID-19 Keywords: COVID 2019 , Retinoic acid, Endosomal toll-like receptor 3,T Cells, IFN type1, AT1, ACE2,TMPRSS2,RIG-1.

NCT04353180

Conditions

1. COVID19

Interventions

1. Drug: Drug Isotretinoin (13 cis retinoic acid ) capsules+standard treatment
2. Drug: Isotretinoin(Aerosolized 13 cis retinoic acid) +standard treatment
3. Drug: Standard treatment

Introduction: The COVID-19 pandemic is characterized by significant morbidity and mortality. It is caused by a novel coronavirus with no current specific prevention nor treatment therapies. Treatments have been administered to patients with COVID-19 in order to control viral infection, among them: Chloroquine (CQ) and Hydroxychloroquine (HCQ), Lopinavir/Ritonavir (Lop/r), Remdesivir, Favipavir, Emtricitabine/ Tenofovir acting over bacterial co-infection Azithromycin (Azithro), or modifying the inflammatory response of the host (Tocilizumab, colchicine, dexamethasone, Icatibant, ibuprofen lipidic and by other mechanisms (rosuvastatin) Clinical trials offer conflicting evidence regarding the effectiveness and safety of therapies The real effectiveness and safety profile of the treatments for COVID-19 remains unknown. Objective: Evaluate the effectiveness and safety of pharmacological therapies used to treat adult patients with COVID-19. Methods: Pragmatic randomized controlled trial. Study population: Adults aged 18 years or over with a positive real-time polymerase chain reaction (RT-PCR) or with high suspicion of Severe Acute Respiratory Syndrome CoV-2 (SARS CoV-2) and diagnosis of mild, severe or critical pneumonia, requiring hospital management at six hospitals in Colombia. Exclusion criteria: Pregnancy, known allergy to treatment, cirrhosis or hepatic abnormality (transaminases greater than 5 reference values), glomerular filtration rate lesser than 30 ml/min/1.73m^2, history of lung fibrosis, advanced or metastatic cancer. Sample size: 1,200 participants. The study will be carried out in two phases. The first phase will be conducted with 400 participants and aims to identify treatments with higher or minimum potential, discontinue treatments with higher toxicity and have opportunity of introducing new treatments with potential efficacy. The second phase will be conducted with 1,200 participants to evaluate the effectiveness of the selected treatments. Four interventions have been defined: I1 Emtricitabine/ teneofovir , I2 Colchicine plus rosuvastatin, I3 Emtricitabine/ teneofovir plus Colchicine plus rosuvastatin and I4 standard treatment. Within each institution, participants will be randomly assigned to one of the treatment arms assigned to that institution. Concealment will be kept through software that maintain the assignment concealed until the random assignment is done . Treatment administration will be open. Variables: Sociodemographic and clinical at recruitment; (comorbidities, need for therapeutic support , grade of invasion at admission). Primary outcomes. Effectiveness: Mortality. Safety: Serious adverse events (AE) assessed by the NCI Community Oncology Research Program (NCORP) Guidance for Collection of Adverse Events Related to COVID-19 Infection. Secondary outcomes: Intensive care unit (ICU) admission, requirement of respiratory support, time to death, number of participants cured, any adverse event related to treatment. Analysis: Descriptive for the presentation of summary measures of the basal conditions by type of variable. Bivariate. Description of the basal conditions (with organic failure at admission, without failure at admission), by type of treatment, by participating institution. Description of crude effectiveness and safety by means of the difference of accumulated incidences, each one with 95% confidence intervals (95% CI) Intention to treat analyisis will be done. Adjusted analysis: The ratio and difference of cumulative incidences of mortality at 7 and 28 days and severe adverse events between treatments will be estimated, adjusting for confounding variables using logistic regression models with mixed effects considering each institution as a level or from equations. generalized estimation (GEE). On the other hand, as part of the pragmatic approach, the surface under cumulative ranking curve (SUCRA) will be calculated based on Bayesian theory to define which drug has the highest probability of being the most useful in the management of infection. Ethical considerations: The study has a risk beyond minimum according to the Resolution 8430/1993 of the Colombian Ministry of Health. Informed consent will be explained and signed if the patient is in condition to do so. This protocol will undergo evaluation by the ethics committee at each of the participating institutions and at the National University of Colombia. The protocol follows the Helsinki Declaration and institutional protocols for clinical investigation.

NCT04359095

Conditions

1. COVID-19

Interventions

1. Drug: Emtricitabine/tenofovir
2. Drug: Colchicine Pill
3. Drug: Rosuvastatin
4. Other: Standard treatment

The study hypothesis is that cyclosporine, added to standard treatment of hospitalized patients with COVID19 infection may improve their prognosis.

NCT04392531

Conditions

1. COVID19 Infection

Interventions

1. Drug: Cyclosporine
2. Drug: Standard treatment

MeSH:Infection

Patients with COVID-19 associated ARDS and mechanical ventilation have a high mortality. Part of the disease is an activation of the coagulation system which seems to contribute to clotformation in the pulmonary bloodstream. Recently we implemented an algorithm applying higher doses of heparins (LMWH). However, this approach could not inhibit clotformation enough. Bivalirudin could prevent clotformation better and support dissolving existing clots. Therefore, we want to compare 50 patients with the standard treatment with 50 patients under bivalirudin treatment which we normally apply in patients with a HIT-syndrome. Our primary outcome measure is oxygenation reflected as P/F ratio.

NCT04445935

Conditions

1. Anticoagulation in COVID-19 ARDS

Interventions

1. Drug: Bivalirudin Injection
2. Drug: Standard treatment

MeSH:Stress, Psychological

This study is a multi-center randomized, controlled, and blinded clinical trial study that will be performed in four medical-educational centers. In this study, the samples will be selected from among patients with SARS-CoV-2 as easy access and based on entry criteria and will be randomly divided into two groups, including a control group and an intervention group. The study will be conducted in four medical centers. From each center, 56 definitive Corona patients will be selected, who will be randomly divided into two groups of 28, for a total of 224 patients will enter the study. In the intervention group, in addition to receiving the test spray, Patients will also receive standard treatment

NCT04463420

Conditions

1. COVID-19

Interventions

1. Drug: PHR160 Spray
2. Drug: Placebo
3. Drug: Standard treatment

Combination of Chemopreventive agents (All- Trans Retinoic Acid and Tamoxifen) as potential treatment for the Lung Complication of COVID-19 Abstract Angiotensin-converting enzyme (ACE2) protein found on the cell membranes is the target of SARS-CoV-2 for entering into the host cells. Viral spike protein-binding with ACE2 down-regulates it. As ACE2 is known to protect the lung from injuries, SARS-CoV-2-induced ACE2 deficiency may expose patients to lung damage. In this Review, we use established and emerging evidence based on the findings of previous studies and researches to propose a testable hypothesis that Combination of chemopreventive agents (All Trans Retinoic acid and Tamoxifen) can be tested to prevent inflammatory complication in severe acute respiratory syndrome coronavirus 2 infection via two mechanisms by inhibiting bradykinin B1,B2 receptors expression and upregulating the depleted ACE2 in COVID-19 . Bradykinin B1 receptors are not expressed under physiological conditions but are induced under inflammatory conditions. Here we hypothesize that permanent attack and invasion of COVID-19 to lung epithelial cells via binding to ACE2 leads to tissue injury and inflammation and that increases BK levels and BK-B2-receptor (B2R) stimulation A study reported that tissue injury and inflammation increases BK levels and BK-B2-receptor (B2R) stimulation. We suggest that Bradykinin mediates and induces lung injury, proinflammatory cytokines and inflammation likely precipitates life threatening respiratory complications in COVID-19. Further experiments showed that BK treatment stimulated IL-6 production On the other hand a study reported that cells treated with Retinoic acid and Tamoxifen for 48 h significantly decreased the BK-B2 receptor protein levels (70.3 ± 0.6% vs. 100% of control, P < 0.05). Retinoids inhibit bradykinin B1 receptor-sensitized responses and this action could participate in their anti-inflammatory and immunomodulatory effects. In addition retinoic acid, is known to possess in vivo anti-inflammatory, anti-platelet and fibrinolytic activities. A study investigated the in vitro thrombin and platelet aggregation inhibitory activities of retinoic acid and retinaldehyde.Retinoic acid, retinaldehyde and retinol exhibited potent inhibition of thrombin, with IC50 values of 67μg/ml, 74μg/ml and 152μg/ml, respectively for the inhibition of thrombin (Sigma); and 49μg/ml, 74μg/ml and 178μg/ml, respectively for the inhibition of thrombin (plasma). Amongst vitamin A and its derivatives, retinoic acid showed the highest inhibition of both the forms of thrombin. Beside the effectiveness of TAM on cancer cells, it also has other effects on numerous microbes including parasite, fungi, bacteria, and some viruses such as Ebola virus and human immunodeficiency virus (HIV).Furthermore Tamoxifen can block the action of interleukin 6 and inhibit neutrophils. A study demonstrated that tamoxifen has side effects associated with neutropenia. Since tamoxifen can cause neutropenia and subsequently influence the neutrophil-to-lymphocyte ratio (NLR) value In addition it has anti malarial effect similar to chloroquine In conclusion Keywords: COVID 2019 , Retinoic acid, Endosomal toll-like receptor 3,T Cells, IFN type1, AT1, ACE2,TMPRSS2

NCT04568096

Conditions

1. the Lung Complication of COVID-19

Interventions

1. Combination Product: Aerosolized All-Trans Retinoic acid plus oral Tamoxifen
2. Other: Standard treatment