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).