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

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

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: IV Dexamethasone; Drug: Nasal Dexamethasone

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 2

Contacts and Locations

Study Locations

• Mexico
  • Cdmx
    • Mexico City, Cdmx, Mexico, 06720
      • Hospital General de México Dr. Eduardo Liceaga
    • Mexico City, Cdmx, Mexico, 14080
      • Instituto Nacional de Cardiologia Ignacio Chavez
    • Mexico City, Cdmx, Mexico, 14269
      • El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Edda Sciutto Conde
• Collaborators: Instituto Nacional de Cardiologia Ignacio Chavez; Hospital General de México Dr. Eduardo Liceaga; El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez
• Investigators: Principal Investigator: Edda Sciutto, PhD, Instituto de Investigaciones Biomédicas, UNAM

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2021
• Primary Completion (Actual): November 12, 2021
• Study Completion (Actual): November 13, 2021

Study Registration Dates

• First Submitted: August 12, 2020
• First Submitted That Met QC Criteria: August 12, 2020
• First Posted (Actual): August 14, 2020

Study Record Updates

• Last Update Posted (Actual): December 14, 2022
• Last Update Submitted That Met QC Criteria: December 12, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: COVID-19; Dexamethasone; Severe Acute Respiratory Syndrome; SARS CoV-2 infection; Nasal administration
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101
• Other Study ID Numbers: DI/20/407/04/36

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Information exchange for research purposes
• IPD Sharing Time Frame: Upon study completion, by request
• IPD Sharing Supporting Information Type: Study Protocol; Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No