Phase II first stage (II/1): compare the effect of treatment with single antivirals against placebo in reducing the load of SARS-CoV-2 in nasopharyngeal swab samples |
Decay rate (slope) of the SARS-CoV-2 viral load logarithm in nasopharyngeal and swab samples evaluated at D0, D3, D6 and D10 after randomization |
Phase II second stage (II/2): compare the effect of treatment with combinations of antivirals compared to isolated ones in reducing the SARS-CoV-2 viral load in nasopharyngeal swab samples |
Decay rate (slope) of the SARS-CoV-2 viral load logarithm in nasopharyngeal and swab samples evaluated at D0, D3, D6 and D10 after randomization |
Phase III: compare the efficacy of antivirals alone or in combination to the placebo in increasing the number of days free of respiratory support |
Days free of respiratory support, defined as the number of days without oxygen, noninvasive ventilation/high-flow nasal cannula or the need for mechanical ventilation within 15 days from randomization 1. This parameter is counted as follows: D = zero (if the patient dies within 15 days (either in the hospital or at home or remains on respiratory support with oxygen through a nasal catheter, noninvasive ventilation, high-flow nasal catheter, or mechanical ventilation ≥ 15 days) D = 15 - x (if the patient is released from the hospital in < 15 days, where x represents the number of days with respiratory support during hospitalization) |
Secondary objectives |
Outcomes/secondary variables |
Evaluate the status using the 7-stage ordinal scale for clinical outcomes on D15 |
Percentage of patients in various stages: 1. Not hospitalized with resumption of normal activities 2. Not hospitalized, but unable to resume normal activities 3. Hospitalized, with no need for supplemental oxygen 4. Hospitalized, requiring supplemental oxygen 5. Hospitalized, requiring high-flow nasal oxygen therapy, noninvasive mechanical ventilation, or both 6. Hospitalized, requiring blood oxygenation through a membrane system, invasive mechanical ventilation or both 7. Death |
Evaluate the status using the 6-stage ordinal scale for clinical outcomes on D7 |
Percentage of patients in various stages: 1. Nonhospitalized 2. Hospitalized, with no need for supplemental oxygen 3. Hospitalized, requiring supplemental oxygen 4. Hospitalized, requiring high-flow nasal oxygen therapy, noninvasive mechanical ventilation, or both 5. Hospitalized, requiring blood oxygenation through a membrane system, invasive mechanical ventilation or both 6. Death |
Evaluate 28-day mortality |
Percentage of deaths in 28 days |
Evaluate the number of days free from mechanical ventilation within 28 days |
D = 28 - number of days requiring mechanical ventilation D = zero if death occurs or the patient continues to require mechanical ventilation after 28 days |
Evaluate the number of days out of the hospital within 28 days |
D = 28 - number of days after admission to the hospital D = zero if death occurs or the patient remains hospitalized after 28 days |
Evaluate the time to discharge |
Number of days from randomization to discharge, within 28 days D = 28 - number of days from randomization to hospital discharge D = zero if death occurs or the patient remains hospitalized after 28 days |
Evaluate the number of days free of respiratory support within 15 days for Phases II/1 and II/2 |
D = 15 - number of days with respiratory support on hospitalization D = zero if death occurs or the patient remains hospitalized with a need for respiratory support defined as the use of low-flow, high-flow oxygen, IMV, or MV in 15 days |
Safety objective |
Outcomes/safety variables |
Evaluate Grade 2, 3 or 4 adverse events, which were not present at the patient’s entrance, defined by the Division of AIDS table for Grading the Severity of Adult and Pediatric Adverse Events(88 National Institute of Allergy and Infectious Diseases (NIH). Division of AIDS (DAIDS). Regulatory Support Center (RSC). DAIDS Adverse Event Grading Tables. DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 - July 2017 [cited 2022 Feb 2]. Available from: https://rsc.niaid.nih.gov/clinical-research-sites/daids-adverseevent-grading-tables https://rsc.niaid.nih.gov/clinical-resea...
) |
Percentage of Grade 2, 3, or 4 adverse events in the Division of AIDS table |
Evaluate serious adverse events Percentage of serious adverse events |
Evaluate discontinuation of study drug-related treatment Percentage of patients who needed to discontinue the intervention (study drug) |