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Journal articles on the topic 'Xanthines – therapeutic use'

Author: Grafiati

Published: 4 June 2021

Last updated: 2 February 2022

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1

Cazzola, Mario, Luigino Calzetta, Peter J. Barnes, Gerard J. Criner, Fernando J. Martinez, Alberto Papi, and Maria Gabriella Matera. "Efficacy and safety profile of xanthines in COPD: a network meta-analysis." European Respiratory Review 27, no. 148 (May 2, 2018): 180010. http://dx.doi.org/10.1183/16000617.0010-2018.

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Theophylline can still have a role in the management of stable chronic obstructive pulmonary disease (COPD), but its use remains controversial, mainly due to its narrow therapeutic window. Doxofylline, another xanthine, is an effective bronchodilator and displays a better safety profile than theophylline. Therefore, we performed a quantitative synthesis to compare the efficacy and safety profile of different xanthines in COPD.The primary end-point of this meta-analysis was the impact of xanthines on lung function. In addition, we assessed the risk of adverse events by normalising data on safet

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Cicero, Arrigo F. G., Federica Fogacci, Masanari Kuwabara, and Claudio Borghi. "Therapeutic Strategies for the Treatment of Chronic Hyperuricemia: An Evidence-Based Update." Medicina 57, no. 1 (January 10, 2021): 58. http://dx.doi.org/10.3390/medicina57010058.

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This article aims to critically review the evidence on the available therapeutic strategies for the treatment of hyperuricemia. For this reason, several papers were reviewed. Xanthine oxidase inhibitors are the safest and most effective uric acid lowering drugs for the management of chronic hyperuricemia, while the efficacy of uricosuric agents is strongly modulated by pharmacogenetics. Emergent drugs (lesinurad, peglotidase) were found to be more effective for the acute management of refractory hyperuricemia, but their use is supported by a relatively small number of clinical trials so that f

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Cicero, Arrigo F. G., Federica Fogacci, Masanari Kuwabara, and Claudio Borghi. "Therapeutic Strategies for the Treatment of Chronic Hyperuricemia: An Evidence-Based Update." Medicina 57, no. 1 (January 10, 2021): 58. http://dx.doi.org/10.3390/medicina57010058.

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This article aims to critically review the evidence on the available therapeutic strategies for the treatment of hyperuricemia. For this reason, several papers were reviewed. Xanthine oxidase inhibitors are the safest and most effective uric acid lowering drugs for the management of chronic hyperuricemia, while the efficacy of uricosuric agents is strongly modulated by pharmacogenetics. Emergent drugs (lesinurad, peglotidase) were found to be more effective for the acute management of refractory hyperuricemia, but their use is supported by a relatively small number of clinical trials so that f

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4

Ahmad, Saeed, Ejaz Mohiuddin, Syed Muhammad Ali Shah, Muhammad Akram, Muhammad Amjad, Jaweria Nisar, Muhammad Riaz, Naveed Munir, and Ghulam Rasool. "Therapeutic Efficacy of Urinile Against Gouty Arthritis." Dose-Response 18, no. 4 (October 1, 2020): 155932582094693. http://dx.doi.org/10.1177/1559325820946934.

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Gout is arthritis caused due to Monosodium urate (MSU) crystals deposition occurring particularly in patients with associated comorbidities limiting the use of conventional therapies. This study was planned to evaluate the therapeutic efficacy of urinile (a herbal drug) for the treatment of gouty arthritis. Allopurinol was used as standard drug (positive control). The study population of 250 volunteers (gouty arthritis patients) were divided into 2 groups as test and control group (n = 125 each). Gouty arthritis patients in test and control group were treated with 300 mg each of urinile and al

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Shen, Z., C. Colton, R. Yan, E. Polvent, V. Hingorani, S. Yan, and L. T. Yeh. "POS1128 COMBINATION TREATMENT OF AR882, A NEW URAT1 INHIBITOR, AND XANTHINE OXIDASE INHIBITORS ALLOPURINOL OR FEBUXOSTAT: EFFECT ON URIC ACID, HYPOXANTHINE AND XANTHINE IN PLASMA OR SERUM AND URINE." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 843.2–843. http://dx.doi.org/10.1136/annrheumdis-2021-eular.1215.

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Background:Xanthine oxidase inhibitors (XOI) are commonly used as urate lowering therapy (ULT) for the treatment of gout. Allopurinol, the first-line treatment, demonstrates low response rate (< 40%), defined as serum urate (sUA) lowering effect below 6 mg/dL, in multiple large-scale clinical trials. As recommended in EULAR guidelines and other literatures, targeting sUA <5 mg/dL or even <4 mg/dL, provides a better opportunity to lower incidence of gout flare and resolution of tophi in gout patients. Febuxostat, a more potent XOI, has been classified as a second-line ULT agent due to

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Aouffen, M'hammed, Joanne Paquin, Eric De Grandpré, Réginald Nadeau, and Mircea-Alexandru Mateescu. "Deglycosylated ceruloplasmin maintains its enzymatic, antioxidant, cardioprotective, and neuronoprotective properties." Biochemistry and Cell Biology 79, no. 4 (August 1, 2001): 489–97. http://dx.doi.org/10.1139/o01-125.

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Ceruloplasmin (CP), an important serum antioxidant, is a blue copper glycoprotein with ferroxidase and oxidase activities. Among other physiological actions, plasma CP was shown to protect isolated rat hearts and cultured P19 neurons exposed to oxidative stress conditions, raising the possibility of using this protein in the treatment of cardiac and neuronal diseases related to oxidative damage. However, since therapeutic applications of CP must be compatible with restrictions in the administration of blood derivatives to humans, there is a need to produce the protein by genetic engineering. T

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Munteanu, Mircea, Adrian Sturza, Adalbert Schiller, and Romulus Timar. "Endothelial Dysfunction in Diabetes – Clasic Sources of Vascular Oxidative Stress (Nadph Oxidases, Enos Uncoupling and Xanthine Oxidase)." Romanian Journal of Diabetes Nutrition and Metabolic Diseases 20, no. 2 (June 1, 2013): 149–55. http://dx.doi.org/10.2478/rjdnmd-2013-0019.

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Abstract Cardiovascular disease is the leading cause of disease / mortality worldwide. It is generally accepted that increased production of reactive oxygen species (ROS) has an important role in cardiovascular pathology, contributing to endothelial dysfunction and to the aggravation of atherosclerosis. Among all cardiovascular risk factors, diabetes mellitus is one of the most important. The worldwide prevalence of diabetes has increased rapidly even in developing countries, doubling the combined risk of cardiovascular events in patients with hypertension. In diabetes, increased reactive oxyg

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Mozgovaya, E., S. Bedina, A. Trofimenko, M. Mamus, S. Spitsina, and I. Zborovskaya. "AB0061 ALTERATIONS OF XANTHINE OXIDOREDUCTASE ACTIVITY IN RED BLOOD CELLS AFTER GLUCOCORTICOID TREATMENT IN RHEUMATOID ARTHRITIS." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1062.1–1062. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3168.

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Background:According to modern concepts, rheumatoid arthritis (RA) refers to severe autoimmune rheumatic diseases. The activation of free radical oxidation processes is essential in the development of this disease [1]. Xanthine oxidoreductase is a significant reactive oxygen species source [2]. Despite the great advances in the treatment of rheumatoid arthritis (RA) associated with the introduction of innovative drugs and especially the improvement of the strategy for their use into clinical practice, glucocorticoids still remain an important component of RA pharmacotherapy in actual clinical

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Mokra, Daniela, and Juraj Mokry. "Phosphodiesterase Inhibitors in Acute Lung Injury: What Are the Perspectives?" International Journal of Molecular Sciences 22, no. 4 (February 16, 2021): 1929. http://dx.doi.org/10.3390/ijms22041929.

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Despite progress in understanding the pathophysiology of acute lung damage, currently approved treatment possibilities are limited to lung-protective ventilation, prone positioning, and supportive interventions. Various pharmacological approaches have also been tested, with neuromuscular blockers and corticosteroids considered as the most promising. However, inhibitors of phosphodiesterases (PDEs) also exert a broad spectrum of favorable effects potentially beneficial in acute lung damage. This article reviews pharmacological action and therapeutical potential of nonselective and selective PDE

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Auberval, Nathalie, Stéphanie Dal, William Bietiger, Elodie Seyfritz, Jean Peluso, Christian Muller, Minjie Zhao, et al. "Oxidative Stress Type Influences the Properties of Antioxidants Containing Polyphenols in RINm5F Beta Cells." Evidence-Based Complementary and Alternative Medicine 2015 (2015): 1–11. http://dx.doi.org/10.1155/2015/859048.

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Thein vitromethods currently used to screen bioactive compounds focus on the use of a single model of oxidative stress. However, this simplistic view may lead to conflicting results. The aim of this study was to evaluate the antioxidant properties of two natural extracts (a mix of red wine polyphenols (RWPs) and epigallocatechin gallate (EGCG)) with three models of oxidative stress induced with hydrogen peroxide (H2O2), a mixture of hypoxanthine and xanthine oxidase (HX/XO), or streptozotocin (STZ) in RINm5F beta cells. We employed multiple approaches to validate their potential as therapeutic

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Hu, Weilei, Guosheng Wang, Lonny B. Yarmus, and Yuan Wan. "Combined Methylome and Transcriptome Analyses Reveals Potential Therapeutic Targets for EGFR Wild Type Lung Cancers with Low PD-L1 Expression." Cancers 12, no. 9 (September 3, 2020): 2496. http://dx.doi.org/10.3390/cancers12092496.

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Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 have demonstrated remarkable treatment efficacy in advanced non-small cell lung cancer (NSCLC). However, low expression of programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) wild-type NSCLCs are refractory, and only few therapeutic options exist. Currently, combination therapy with ICIs is frequently used in order to enhance the treatment response rates. Yet, this regimen is still associated with poor treatment outcome. Therefore, identification of potential therapeutic targets for this subgroup of NSCLC is strong

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Mukhopadhyay, Partha, Mohanraj Rajesh, Sándor Bátkai, Yoshihiro Kashiwaya, György Haskó, Lucas Liaudet, Csaba Szabó, and Pál Pacher. "Role of superoxide, nitric oxide, and peroxynitrite in doxorubicin-induced cell death in vivo and in vitro." American Journal of Physiology-Heart and Circulatory Physiology 296, no. 5 (May 2009): H1466—H1483. http://dx.doi.org/10.1152/ajpheart.00795.2008.

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Doxorubicin (DOX) is a potent available antitumor agent; however, its clinical use is limited because of its cardiotoxicity. Cell death is a key component in DOX-induced cardiotoxicity, but its mechanisms are elusive. Here, we explore the role of superoxide, nitric oxide (NO), and peroxynitrite in DOX-induced cell death using both in vivo and in vitro models of cardiotoxicity. Western blot analysis, real-time PCR, immunohistochemistry, flow cytometry, fluorescent microscopy, and biochemical assays were used to determine the markers of apoptosis/necrosis and sources of NO and superoxide and the

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13

Nowacka-Jechalke, Natalia, Renata Nowak, Marta Kinga Lemieszek, Wojciech Rzeski, Urszula Gawlik-Dziki, Nikola Szpakowska, and Zbigniew Kaczyński. "Promising Potential of Crude Polysaccharides from Sparassis crispa against Colon Cancer: An In Vitro Study." Nutrients 13, no. 1 (January 6, 2021): 161. http://dx.doi.org/10.3390/nu13010161.

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The aim of the present study was to evaluate in vitro the beneficial potential of crude polysaccharides from S. crispa (CPS) in one of the most common cancer types—colon cancer. The determination of the chemical composition of CPS has revealed that it contains mostly carbohydrates, while proteins or phenolics are present only in trace amounts. 1H NMR and GC–MS methods were used for the structural analysis of CPS. Biological activity including anticancer, anti-inflammatory and antioxidant properties of CPS was investigated. CPS was found to be non-toxic to normal human colon epithelial CCD841 C

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14

Pasina, Luca, Barbara Brignolo Ottolini, Laura Cortesi, Mauro Tettamanti, Carlotta Franchi, Alessandra Marengoni, Pier Mannuccio Mannucci, and Alessandro Nobili. "Need for Deprescribing in Hospital Elderly Patients Discharged with a Limited Life Expectancy: The REPOSI Study." Medical Principles and Practice 28, no. 6 (2019): 501–8. http://dx.doi.org/10.1159/000499692.

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Objective: Older people approaching the end of life are at a high risk for adverse drug reactions. Approaching the end of life should change the therapeutic aims, triggering a reduction in the number of drugs.The main aim of this study is to describe the preventive and symptomatic drug treatments prescribed to patients discharged with a limited life expectancy from internal medicine and geriatric wards. The secondary aim was to describe the potentially severe drug-drug interactions (DDI). Materials and Methods: We analyzed Registry of Polytherapies Societa Italiana di Medicina Interna (REPOSI)

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15

Cerchietti, Leandro, Chen Qiuying, ShaoNing Yang, Wang Chunjie, and Steven Gross. "Serum Metabolomics Uncovers a New Therapeutic Target in Diffuse Large B Cell Lymphoma (DLBCL)." Blood 120, no. 21 (November 16, 2012): 1648. http://dx.doi.org/10.1182/blood.v120.21.1648.1648.

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Abstract Abstract 1648 DLBCL is a molecularly heterogeneous disease usually treated with chemoimmunotherapy ultimately curing ∼65% of pts. In order to improve therapy for these pts, the identification of broadly relevant therapeutic targets is critical. One such target is HSP90. Tumor cells are enriched for a fraction of HSP90 found in higher-order multi-chaperone complexes. Tumor-enriched HSP90 (teHSP90) displays higher affinity for HSP90 inhibitors than normal tissues, which contain latent, uncomplexed HSP90. Many client proteins are depleted upon exposure to teHSP90 inhibitors. PU-H71 is a

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16

Yao, Jianbiao, Houhong He, Jin Xue, Jianfang Wang, Huihui Jin, Jian Wu, Jiangning Hu, Ruwei Wang, and Kenny Kuchta. "Mori Ramulus (Chin.Ph.)—the Dried Twigs of Morus alba L./Part 1: Discovery of Two Novel Coumarin Glycosides from the Anti-Hyperuricemic Ethanol Extract." Molecules 24, no. 3 (February 11, 2019): 629. http://dx.doi.org/10.3390/molecules24030629.

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In Traditional Chinese Medicine (TCM), Mori ramulus (Chin.Ph.)—the dried twigs of Morus alba L.—is extensively used as an antirheumatic agent and also finds additional use in asthma therapy. As a pathological high xanthine oxidase (XO, EC 1.1.3.22) activity is strongly correlated to hyperuricemy and gout, standard anti-hyperuremic therapy typically involves XO inhibitors like allopurinol, which often cause adverse effects by inhibiting other enzymes involved in purine metabolism. Mori ramulus may therefore be a promissing source for the development of new antirheumatic therapeutics with less s

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17

Szebeni, János, Lajos Baranyi, Sándor Sávay, Michael Bodó, János Milosevits, Carl R. Alving, and Rolf Bünger. "Complement activation-related cardiac anaphylaxis in pigs: role of C5a anaphylatoxin and adenosine in liposome-induced abnormalities in ECG and heart function." American Journal of Physiology-Heart and Circulatory Physiology 290, no. 3 (March 2006): H1050—H1058. http://dx.doi.org/10.1152/ajpheart.00622.2005.

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Cardiac anaphylaxis is a severe, life-threatening manifestation of acute hypersensitivity reactions to allergens and drugs. Earlier studies highlighted an amplifying effect of locally applied C5a on the process; however, the role of systemic complement (C) activation with C5a liberation in blood has not been explored to date. In the present study, we used the porcine liposome-induced cardiopulmonary distress model for 1) characterizing and quantifying peripheral C activation-related cardiac dysfunction; 2) exploring the role of C5a in cardiac abnormalities and therapeutic potential of C blocka

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BASIVIREDDY, Jayasree, Molly JACOB, and Kunissery A. BALASUBRAMANIAN. "Oral glutamine attenuates indomethacin-induced small intestinal damage." Clinical Science 107, no. 3 (August 24, 2004): 281–89. http://dx.doi.org/10.1042/cs20030390.

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The use of NSAIDs (non-steroidal anti-inflammatory drugs), although of great therapeutic value clinically, is limited by their tendency to cause mucosal damage in the gastrointestinal tract. In the small intestine, the effects these drugs have been shown to produce include inhibition of cyclo-oxygenase, mitochondrial dysfunction and free radical-induced oxidative changes, all of which contribute to the mucosal damage seen. Glutamine is a fuel preferentially used by enterocytes and is known to contribute to maintaining the integrity of these cells. In the present study, we investigated the effe

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Koomen, David C., Joy D. Guingab, Paula S. Oliveira, Bin Fang, Min Liu, Eric A. Welsh, Mark B. Meads, et al. "Proteometabolomics of Melphalan Resistance in Multiple Myeloma." Blood 132, Supplement 1 (November 29, 2018): 5619. http://dx.doi.org/10.1182/blood-2018-99-117747.

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Abstract Although advancements in therapeutic regimens for treating multiple myeloma (MM) have prolonged patient survival, the disease remains incurable. Several classes of drugs have contributed to these improvements, such as proteasome inhibitors, immunomodulators, deacetylase inhibitors, monoclonal antibodies, and alkylating agents including melphalan. An expanded arsenal of diverse chemotherapy targets has improved patient care significantly, yet we still lack sufficient knowledge of how cellular metabolism and drug processing can contribute to drug resistance. To address this issue, we ut

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Vasta, Lauren Marie, Richard C. Zanetti, Dina S. Parekh, Anne B. Warwick, and Kenneth Lieuw. "A Retrospective Review of Mercaptopurine Metabolism Reveals High Rate of Patients with Suboptimal Metabolites Successfully Corrected with Allopurinol." Blood 134, Supplement_1 (November 13, 2019): 3878. http://dx.doi.org/10.1182/blood-2019-126184.

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Introduction: 6-Mercaptopurine (6-MP) is the most frequently used chemotherapy agent in the management of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LL). Skewed drug metabolism can decrease the effectiveness of 6-MP while also resulting in unnecessary toxicities. Each individual's ability to metabolize 6-MP into the desired therapeutic product, 6-thioguanine nucleotide (6-TGN), is directly opposed by the development of the hepatotoxic byproduct, 6-methyl-mercaptopurine (6-MMPN). Certain individuals, referred to as 'shunters,' preferentially generate high levels of 6-MMPN re

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Martorell, Miquel, Xavier Lucas, Pedro Alarcón-Zapata, Xavier Capó, Maria Magdalena Quetglas-Llabrés, Silvia Tejada, and Antoni Sureda. "Targeting xanthine oxidase by natural products as a therapeutic approach for mental disorders." Current Pharmaceutical Design 26 (June 21, 2020). http://dx.doi.org/10.2174/1381612826666200621165839.

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: Mental disorders comprise diverse human pathologies including depression, bipolar affective disorder, schizophrenia, and dementia that affect millions of people around the world. The causes of mental disorders are unclear but growing evidence suggests that oxidative stress and the purine/adenosine system play a key role in their development and progression. Xanthine oxidase (XO) is a flavoprotein enzyme essential for the catalysis of the oxidative hydroxylation of purines -hypoxanthine and xanthine- to generate uric acid. As a consequence of the oxidative reaction of XO, reactive oxygen spec

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Kaur, Jaspreet, Shahaf Tuler, and Constantin A. Dasanu. "Acute gout flare of bilateral first metatarsophalangeal joints due to ibrutinib use in chronic lymphocytic leukemia." Journal of Oncology Pharmacy Practice, July 5, 2021, 107815522110297. http://dx.doi.org/10.1177/10781552211029703.

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Introduction Bruton tyrosine kinase inhibitors represent important tools in the therapeutic armamentarium against chronic lymphocytic leukemia (CLL) and other B-lymphoproliferative disorders. Case Report We describe herein a unique 65-year-old patient who presented with bilateral foot pain four months after starting treatment with ibrutinib for CLL. Of note, the patient had previously been diagnosed with gout, and was taking allopurinol prophylactically at the time of the event. Compliance with allopurinol was in excess of 99%. Yet, he was diagnosed with acute gout flare of bilateral first met

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Basnet, Rajesh, Sandhya Khadka, Buddha Bahadur Basnet, Til Bahadur Basnet, Buddhi Bal Chidi, Sanjeev Nirala, Radheshyam Gupta, and Bidur Sharma. "Xanthine Oxidase and Transforming Growth Factor Beta-activated Kinase 1: potential Targets for Gout Intervention." Current Rheumatology Reviews 16 (November 26, 2020). http://dx.doi.org/10.2174/1573397116666201126162202.

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Background: Gout, an inflammatory arthritis, caused by the deposition of monosodium urate crystals into affected joints and other tissues has become one of the major health problems of today's world. The main risk factor for gout is hyperuricemia, which may be caused by excessive or insufficient excretion of uric acid. The incidence is usually in the age group of 30- 50 years, commonly in males. In developed countries, the incidence of gout ranges from 1 to 4%. Despite effective treatments, there has been an increase in the number of cases over the past few decades. Objective: In recent years,

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AHMANE, Nadjia, Dina ATMANI-KILANI, Nassima CHAHER, Karima AYOUNI, Meriem RAHMANI-BERBOUCHA, Grégory DA COSTA, Nadjet DEBBACHE-BENAIDA, Tristan RICHARD, and Djebbar ATMANI. "Identification of bioactive compounds from Fraxinus angustifolia extracts with anti-NADH oxidase activity of bovine milk xanthine oxidoreductase." TURKISH JOURNAL OF BIOLOGY, April 5, 2019, 133–47. http://dx.doi.org/10.3906/biy-1810-26.

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Fraxinus angustifolia leaves and bark are used in traditional medicine against various inflammatory-related pathologies incumbent to reactive oxygen species (ROS) generation by the NADH oxidase activity of enzymes such as xanthine oxidoreductase (XOR). This study was designed to investigate the in vitro and in vivo inhibitory activities of this enzyme by Fraxinus angustifolia extracts. The leaf organic phase of ethyl acetate (LFA) and its bark aqueous counterpart (BFA) showed the strongest anti-NADH oxidase activity in vitro (IC50 = 38.51 and 42.04 μg mL-1, respectively). They consequently sup

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Kalu, E. C., C. C. Ikwwuchi, E. O. Ayalogu, and K. T. Nwauche. "Proximate and Phytochemical Profile of Melanthera biflora Leaves." International Journal of Biochemistry Research & Review, May 10, 2019, 1–12. http://dx.doi.org/10.9734/ijbcrr/2019/v25i430082.

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The proximate and phytochemical composition of Melanthera biflora was investigated, using standard methods. From the obtained results the leaves had high moisture contents (71.1± 0.2%) and crude fiber (3.91 ± 0.5) while containing moderate protein (7.0 ± 0.03%), while containing lipid (1.10 ± 4%), ash (2.8 ± 0.2%), total carbohydrate (6.09 ± 0.2%) and caloric value (62.26±0.14 kcal/100g). Eleven Phytochemical families were detected with tannin as the most abundant (27.82%) consisting 100% tannic acid. Thirteen alkaloids (13.65%) were detected consisting mainly of morphine (28.05%), methylmorph

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Grammatis, A., E. X. Georgiou, and C. M. Becker. "O-134 Cochrane review on the effect of pentoxifylline for endometriosis." Human Reproduction 36, Supplement_1 (July 1, 2021). http://dx.doi.org/10.1093/humrep/deab126.059.

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Abstract Study question To assess the effect of pentoxifylline, a methyl-xanthine with anti-inflammatory effects, for the management of premenopausal women with endometriosis. Summary answer There is not enough evidence to support the use of pentoxifylline in the management of premenopausal women with endometriosis to improve fertility and pain outcomes. What is known already Endometriosis is a chronic, inflammatory condition that occurs mainly during the reproductive years. It is characterized by endometrium-like tissue developing outside the uterine cavity. This endometriotic tissue developm

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Bosaeed, Mohammad, Ebrahim Mahmoud, Mohammad Hussein, Ahmad Alharbi, Abdulrahman Alsaedy, Adel Alothman, Majed Aljeraisy, et al. "A Trial of Favipiravir and Hydroxychloroquine combination in Adults Hospitalized with moderate and severe Covid-19: A structured summary of a study protocol for a randomised controlled trial." Trials 21, no. 1 (October 31, 2020). http://dx.doi.org/10.1186/s13063-020-04825-x.

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Abstract Objectives The selected combination was based on limited evidence clinically and in vitro on the efficacy of the Favipiravir and Hydroxychloroquine in SARS-CoV-2. The two medications were listed in many guidelines as treatment options and ongoing trials assessing their efficacy and safety. Thus, we want to prove the clinical effectiveness of the combination as therapy. Trial design This is an Open label, multicenter, randomized controlled clinical trial to evaluate the safety and efficacy of novel therapeutic agents in hospitalized adults diagnosed with COVID-19. It is a multicenter t

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