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

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

Detailed Description
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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.

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

Conditions
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Covid19

Intervention / Treatment
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* Drug: IV Dexamethasone
* Drug: Nasal Dexamethasone


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Multicenter, randomized, controlled trial adult patients with confirmed COVID-19 infection
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard therapy (ST) only<br>Control. Standard care and treatment only | Drug: IV Dexamethasone<br>* 6 mg from Day 1 to 10 after randomization<br>* Other names: ST;|
| Experimental: DXM<br>Nasal dexamethasone plus Standard care and treatment | Drug: Nasal Dexamethasone<br>* 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.<br>* Other names: Nasal DXM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time of clinical improvement | Evaluation of the clinical status of patients after randomization, defined as a two point improvement in the WHO 7-point Ordinal Scale | 10 days after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time-to-death from all causes | All-cause mortality rates at 28 days after randomization | 28 days after randomization | 
| Time free from mechanical ventilation | Ventilator-free days, defined as alive and not requiring mechanical ventilation, at 10 days after randomization. | 10 days after randomization | 
| Viral load | Virological measurements, including proportions with detection of viral RNA over time and measurements of viral RNA titer area under the curve (AUC). | 10 days after randomization | 
| Length of hospital stay | Length of hospital stay in days | 10 days after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dexamethasone, SARS CoV-2 infection, COVID-19, Severe Acute Respiratory Syndrome, Nasal administration