Abstract
BackgroundBy end December of 2021, COVID-19 has infected around 276 million individuals and caused over 5 million deaths worldwide. Infection results in dysregulated systemic inflammation, multi-organ dysfunction, and critical illness. Cells of the central nervous system are also affected, triggering an uncontrolled neuroinflammatory response. Low doses of glucocorticoids, administered orally or intravenously, reduce mortality among moderate and severe COVID-19 patients. However, low doses administered by these routes do not reach therapeutic levels in the CNS. In contrast, intranasally administered dexamethasone can result in therapeutic doses in the CNS even at low doses.MethodsThis is an approved open-label, multicenter, randomized controlled trial to compare the effectiveness of intranasal versus intravenous dexamethasone administered in low doses to moderate and severe COVID-19 adult patients. The protocol is conducted in five health institutions in Mexico City. A total of 120 patients will be randomized into two groups (intravenous vs. intranasal) at a 1:1 ratio. Both groups will be treated with the corresponding dexamethasone scheme for 10 days. The primary outcome of the study will be clinical improvement, defined as a statistically significant reduction in the NEWS-2 score of patients with intranasal versus intravenous dexamethasone administration. The secondary outcome will be the reduction in mortality during hospitalization.ConclusionsThis protocol is currently in progress to improve the efficacy of the standard therapeutic dexamethasone regimen for moderate and severe COVID-19 patients.Trial registrationClinicalTrials.govNCT04513184. Registered November 12, 2020. Approved by La Comisión Federal para la Protección contra Riesgos Sanitarios (COFEPRIS) with identification number DI/20/407/04/36. People are currently being recruited.Graphical abstract
Highlights
The outbreak of COVID-19 has infected around 276 million individuals and caused over 5 million deaths worldwide, with a current global case-fatality ratio of 2%
The secondary outcome will be the reduction in mortality during hospitalization. This protocol is currently in progress to improve the efficacy of the standard therapeutic dexamethasone regimen for moderate and severe COVID-19 patients
Other relevant factors include SARS-CoV-2 neurotropism/neuroinvasive [2,3,4,5,6,7,8,9] as viral Ribonucleic acid (RNA) was found in the brain of patients who deceased from severe acute respiratory syndrome due to COVID-19 infection [10,11,12]
Summary
Trial design The “REVIVAL” trial is an interventional, phase 2, multicenter, open-label, randomized controlled study in adult patients with confirmed COVID-19 diagnosis, designed to evaluate the efficacy (superiority) of low doses of intranasal DXM compared to intravenous administration (allocation ratio 1:1) in patients of five COVID-19 referral centers in Mexico City. Sample size and randomization The analysts of the statistic team calculated the size with EPIDAT version 3.1.2 software, using the option “Sample size and surveillance curves” with an estimated 50% increase in the proportion of patients free of mechanical ventilation [intranasal DXM 70% vs intravenous DXM 45%] This value was estimated using the data of the COVID-19 patients registered in Mexican hospitals with a confidence of 95%, power of 80%, and proportion of losses of 10%. Plans to promote participant retention and complete follow-up All participants will receive specialized medical care, including clinical, neurological, and neuropsychological studies These evaluations will be carried out 1, 3, 6, and 12 months after COVID-19 to monitor the evolution of the disease. Interim analysis This analysis will be performed by an independent expert team to examine some relevant data as baseline, safety outcome, and efficacy outcome data to consider ending the study if no trend is observed
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