Study design and participants
TOFA-COV-2 is a multicentre non-randomized controlled study that was conducted in the three clinics of the Sechenov University (Moscow, Russia) in patients with moderately severe COVID-19. The study population consisted of adults (≥18 years) with COVID-19, who were admitted to the university clinics between April 17 and August 1, 2020. A diagnosis of COVID-19 was confirmed by polymerase chain reaction (PCR) and/or chest computed tomography (CT) (4 or 5 on CO-RADS scale) [12]. The extent of bilateral lung involvement (0-24%, 25-49%, 50-74%, ≥75%) was evaluated in the five lung zones according to the anatomical structure of lung: left upper lobe, left lower lobe, right upper lobe, right middle lobe and right lower lobe.
In order to be included in this study, patients had to have COVID-19 involving at least 25% of lung tissue in combination with an oxygen saturation at rest ≤93% on ambient air, increased C-reactive protein (CRP; ≥50 mg/L), and/or fever (≥38.0°C) that persisted for at least two days despite treatment with nonsteroidal anti-inflammatory drugs or paracetamol. Exclusion criteria for the administration of tofacitinib were coexistent infection, requirement for invasive mechanical ventilation, estimated glomerular filtration rate (eGFR) calculated using CKD-EPI formula ≤30 ml/min/1.73 m2, elevated ALT and/or AST levels more than 3 times the upper limit of normal, chronic use of glucocorticoids or immunosuppressive agents, or administration of IL-6 inhibitors and/or high-dose glucocorticoids (≥250 mg prednisone equivalent intravenously) for the treatment of COVID-19. Comparators were selected randomly from the same population using the above criteria.
The study was approved by the Ethical Committee of the Sechenov University. All patients provided written, informed consent for the off-label use of experimental medications, including tofacitinib, according to the provisional recommendations issued by the Russian Ministry of Health during the outbreak of COVID-19. The protocol of the study was registered at clinicaltrials.gov (NCT04750317).