Table 3.
Study procedures; a) Chest computed tomography (CCT) - changes in the thoracic CT image will be analyzed using the The total severity score (TSS) [Li et al., 2020] or chest X-ray examination (as decided by the attending physician). b) Hematology: hemoglobin, morphology with smear, ESR. c) Biochemistry: C-reactive protein; α-hydroxybutarate dehydrogenase (HBDH); creatinine with GFR (Glomerular Filtration Rate) calculation, pro-calcitonin, LDH, ALT, AST; D-dimers; fibrinogen, ferritin, interleukin-6 d) Only for women of childbearing age e) If not made at diagnosis f) We will conduct a clinical assessment of respiratory fitness every day for 14 days of the study duration with SO2 measurement every 8 h and based on the WHO recommended 7-point scale for clinical improvement (OSCI) (1-line criterion) and general condition assessment questionnaires health (PROMIS Global Health Scale) (2-line criterion). Measurement of SO2 does not apply to patients discharged home. g) ECG during the rest phase and after 1 min of light effort with the assessment of saturation h) ECG should be performed 1 and 3 weeks after the start of therapy (measurement together with QTC determination by Bazett's method). An ECG should also be done before increasing the dose and two weeks after each dose increase. Ultimately, however, it is up to the attending physician to decide. *** Day 30 is a follow-up visit - if all procedures cannot be performed (the patient ends drug / placebo on day 15) or the post-treatment visit in the open part two with a positive SAR-CoV-2 antigen test on day 15 maintenance of symptoms) - treatment could be continued for another 14 days in the open label phase after the decision of the attending physician. This visit does not apply to patients who have completed all Day 15 procedures and have entered the open-label phase. i) In the case of hospitalization of the patient or an outpatient visit, the attending physician will decide to perform the procedure.
| Screening |
Randomization visit |
Monitoring visits |
Final visit |
|
|---|---|---|---|---|
| Time point | Day −5 to Day 1 | Day 1 (D1) |
Day 2–14 (D2-D14) |
Day 15 (Day 30***) (D15; D30) |
| Procedures | ||||
| Informed consent | x | |||
| Demigraphic and medical history | x | |||
| Inclusion and exclusion criteria assessment | x | x | ||
| Confirmation of positive test for SARS-CoV-2 infection | x | |||
| Physical examination | x | x | xi | x |
| Neurological examination | x | x | x | |
| Vital signs assessment | x | x | xi | x |
| Height | x | |||
| Weight, Body Mass Index (BMI) | x | x | x | |
| Computed tomography/X-ray of chest a | x | x | ||
| Hematologyb | x | x | ||
| Biochmistryc | x | x | ||
| Pregnancy test in blood d | x | |||
| Pregnancy test in urine d | x | x | ||
| SARS-CoV-2 test (PCR or antygen) | xe | x | ||
| SARS-CoV-2 antibodies in serum | x optional | X | ||
| Electrocardiography | x | x | ||
| Vital signs | xg | x | xh | xh |
| Drug compliance | xf | xf | xf | xf |
| PROMIS Global Health Scale | x | x | x*** | |
| WHO scale | x | x | ||
| Fatigue Severity Scale | x | x | x | x |
| Beck Depression Inventory | x | x | ||
| Visual Analogue Scale | x | x | ||
| The Epworth Sleepiness Scale | x | x | ||
| The Short Form-36 Health Survey Questionnaire | x | x | ||
| Adverse effects (AE/ SAE) |
x | x | ||
| Adjunctive treatment review | x | x | x | |
| SARS-CoV-2 test (PCR or antigen) | x | x | x |