Randomized Clinical Trial of Intranasal Dexamethasone as an Adjuvant in Patients With COVID-19

Hospital General de México Dr. Eduardo Liceaga, Instituto Nacional de Cardiologia Ignacio Chavez, El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez

This Clinical Trial evaluates nasal administration of Dexamethasone as an adjuvant treatment strategy for non-critically ill hospitalized participants with SARS CoV-2 infection.

Approximately 30% of the admitted patients with Covid-19 require admission to the intensive care unit for respiratory assistance, ranging from a high flow nasal cannula to invasive ventilation. These patients are affected by respiratory dysfunctions and even dysfunction of the brain respiratory control centers. Additionally, exacerbated inflammation leads to endothelial and coagulation disorders that aggravate the course of the illness. No effective therapy has yet been found to treat forms SARS-CoV-2 bass. One of the adjunctive therapeutic alternatives addressed is the use of intravenously administered glucocorticoids (GC), aimed at reducing exacerbated peripheral inflammation. They have been used at early stages of infection in high doses and with controversial results. In our laboratory at the Biomedical Research Institute from the National Autonomous University of Mexico (UNAM), we have shown that dexamethasone, a GC (DXM) administered intranasally, reaches the central nervous system through the olfactory nerve (alike various pathogens, including coronaviruses) and reduces neuroinflammation more effectively than when applied intravenously. Additionally, biodistribution studies indicate that the DXM is detectable from the first minute after its application, both in the central nervous system and in the respiratory system. The objective of this study is to evaluate the safety, efficacy and tolerability of dexamethasone in patients hospitalized with SARS-CoV-2 with moderate-severe forms, with an without the requirement of mechanic ventilation, including syndrome of acute respiratory distress or pneumonia (as diagnosed by CAT) with alveolar / interstitial lung involvement.

Dexamethasone, SARS CoV-2 infection, COVID-19, Severe Acute Respiratory Syndrome, Nasal administration

0.12 mg/kg/daily for 3 days from day 1, followed by 0.06 mg/kg/daily from day 4 to 10 after randomization.

Evaluation of the clinical status of patients after randomization, defined as a two point improvement in the WHO 7-point Ordinal Scale

Ventilator-free days, defined as alive and not requiring mechanical ventilation, at 10 days after randomization.

Virological measurements, including proportions with detection of viral RNA over time and measurements of viral RNA titer area under the curve (AUC).

Inclusion Criteria: Positive diagnosis of SARS-CoV-2 by real-time RT-PCR in oropharyngeal sample. 7 days or more after the start of the infection Hospitalized patients with moderate to severe respiratory complications that do not have received mechanical ventilation. Patients receiving standard therapy at the Hospital General de México Eduardo Liceaga. Signing of the informed consent form Patients of both sexes (non-pregnant female) 18 years of age or older will be eligible if they have a positive diagnostic sample by RT-PCR, pneumonia confirmed by chest imaging and oxygen saturation (SaO2) < 93% at ambient air or a ratio of the partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2) (PaO2: FiO2) at 300 mg Hg or less Exclusion Criteria: Patients participating in another research protocol. Patients receiving oral or intravenous glucocorticoids Immunosuppressed patients (including HIV infection) Glaucoma patients. Patients with allergy to dexamethasone. Pregnant or lactating women Concomitant autoimmune diseases Refusal by the patient or family to participate in the study

Cardenas G, Chavez-Canales M, Espinosa AM, Jordan-Rios A, Malagon DA, Murillo MFM, Araujo LVT, Campos RLB, Wong-Chew RM, Gonzalez LER, Cresencio KI, Velazquez EG, de la Cerda MR, Leyva Y, Hernandez-Ruiz J, Hernandez-Medel ML, Leon-Hernandez M, Quero KM, Moncivais AS, Diaz SH, Martinez IRZ, Martinez-Cuazitl A, Salazar INM, Sarmiento EB, Pena AF, Hernandez PS, Reynoso RIA, Reyes DM, Del Rio Ambriz LR, Bonilla RAA, Cruz J, Huerta L, Fierro NA, Hernandez M, Perez-Tapia M, Meneses G, Espindola-Arriaga E, Rosas G, Chinney A, Mendoza SR, Hernandez-Aceves JA, Cervantes-Torres J, Rodriguez AF, Alor RO, Francisco SO, Salazar EA, Besedovsky H, Romano MC, Bobes RJ, Jung H, Soldevila G, Lopez-Alvarenga J, Fragoso G, Laclette JP, Sciutto E. Intranasal dexamethasone: a new clinical trial for the control of inflammation and neuroinflammation in COVID-19 patients. Trials. 2022 Feb 14;23(1):148. doi: 10.1186/s13063-022-06075-5.