Clinical trial NCT04750317: Efficacy and Safety of Tofacitinib in Patients With COVID-19 Pneumonia
Official title: Efficacy and Safety of Tofacitinib in Patients With COVID-19 Pneumonia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: COVID-19
Lead sponsor: I.M. Sechenov First Moscow State Medical University
Sponsor class: OTHER
First posted: 2021-02-11
Enrollment: 414
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: TOFA-COV-2 is a cohort study of the efficacy of tofacitinib in reducing the risk of mechanical ventilation and/or death in patients with moderately severe COVID-19 pneumonia who received standard of care treatment (SoC). The study population consists of adults (≥18 years) with COVID-19, who are admitted to the university hospitals and don't require invasive or noninvasive ventilation on admission. All patients are divided into four groups depending on nadir levels of oxygen saturation and therapy: (1) patients with oxygen saturation ≤93% who received tofacitinib and SoC, (2) patients with oxygen saturation ≤93% who received only SoC, (3) patients with oxygen saturation \>93% who received tofacitinib and SoC, (4) patients with oxygen saturation \>93% who received only SoC. The aim of the study is to test the hypothesis that addition of tofacitinib to SoC could reduce the risk of mechanical ventilation and/or death.

Detailed description: TOFA-COV-2 is a cohort study that is conducted in the three clinics of the Sechenov University (Moscow, Russia) in patients with moderately severe COVID-19 pneumonia. A diagnosis of COVID-19 associated pneumonia suspected clinically was confirmed by polymerase chain reaction (PCR) and/or chest CT. In patients with inconclusive or negative results of PCR on nasopharyngeal swab, SARS-CoV-2 induced pneumonia was defined as an acute respiratory infection with typical CT findings (4 or 5 on CO-RADS scale) and no other obvious aetiology.

In order to be included in this study, patients must have COVID-19 pneumonia involving at least 25% of lung tissue in combination with at least one of the following: (1) oxygen saturation at rest ≤93% on ambient air, (2) increased C-reactive protein (CRP ≥50 mg/L) and/or (3) fever (≥38.0°C) that persisted for at least two days despite treatment with nonsteroidal antiinflammatory drugs or paracetamol. Exclusion criteria for the administration of tofacitinib were coexistent infection other than COVID-19; requirement for invasive mechanical ventilation; estimated glomerular filtration rate 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; and administration of interleukin-6 inhibitors and/or high-dose glucocorticoids (≥250 mg prednisone equivalent intravenously) for the treatment of COVID-19.

All patients are divided into four groups depending on nadir levels of oxygen saturation and therapy: (1) patients with oxygen saturation ≤93% who received tofacitinib and SoC, (2) patients with oxygen saturation ≤93% who received only SoC, (3) patients with oxygen saturation \>93% who received tofacitinib and SoC, (4) patients with oxygen saturation \>93% who received only SoC. The aim of the study is to test the hypothesis that administration of tofacitinib could influence the risk of mechanical ventilation and/or death.

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 infection.

Eligibility criteria: Inclusion Criteria:

1. SARS-CoV2 Infection diagnosed by PCR and/or typical lesions on CT-scan (4 or 5 on CO-RADS scale) in combination with at least one of the following:

   * oxygen saturation at rest ≤93% on ambient air,
   * AND/OR C-reactive protein ≥50 mg/L,
   * AND/OR fever (≥38.0°C) that persisted for at least two days despite treatment with nonsteroidal antiinflammatory drugs or paracetamol
2. Written Informed Consent

Exclusion Criteria:

1. Age \<18 years
2. Coexistent infection other than COVID-19
3. Requirement for invasive mechanical ventilation
4. Estimated glomerular filtration rate calculated using CKD-EPI formula ≤30 ml/min/1.73 m2;
5. Elevated ALT and/or AST levels more than 3 times the upper limit of normal
6. Chronic use of glucocorticoids or immunosuppressive agents
7. Administration of interleukin-6 inhibitors and/or high-dose glucocorticoids (≥250 mg prednisone equivalent intravenously) for the treatment of COVID-19

Primary outcomes:
measure: Death
timeFrame: Within 28 days from admission
measure: Mechanical ventilation
timeFrame: Within 28 days from admission
Secondary outcomes:
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Sechenov First Moscow State Medical University (Sechenov University) - University Clinical Hospital
Study officials:
affiliation: I.M. Sechenov First Moscow State Medical University (Sechenov University)
name: Sergey Moiseev, MD
role: PRINCIPAL_INVESTIGATOR
References: