Efficacy and Safety of Tofacitinib in Patients With COVID-19 Pneumonia

NCT ID: NCT04750317

Last Updated: 2021-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 414 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-11
• Study Completion Date: 2020-09-01

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.

Conditions

COVID-19

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Patients with reduced oxygen saturation ≤93% treated with tofacitinib

Patients with oxygen saturation ≤93% on admission treated with tofacitinib and standard of care treatment

Group Type: EXPERIMENTAL

Tofacitinib

Intervention Type: DRUG

Tofacitinib was administered at a dose 10 mg twice daily on day 1, followed by 5 mg twice daily on day 2-5. The dosage was reduced up to 5 mg once daily in patients with moderate renal impairment or moderate hepatic impairment.

Patients with reduced oxygen saturation treated with SoC

Patients with oxygen saturation ≤93% on admission treated with standard of care only

Group Type: NO_INTERVENTION

No interventions assigned to this group

Patients with preserved oxygen saturation >93% on admission treated with tofacitinib

Patients with oxygen saturation \>93% on admission treated with tofacitinib and standard of care

Group Type: EXPERIMENTAL

Tofacitinib

Intervention Type: DRUG

Tofacitinib was administered at a dose 10 mg twice daily on day 1, followed by 5 mg twice daily on day 2-5. The dosage was reduced up to 5 mg once daily in patients with moderate renal impairment or moderate hepatic impairment.

Patients with preserved oxygen saturation >93% on admission treated with SoC

Patients with oxygen saturation \>93% on admission treated with standard of care only

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Tofacitinib

Tofacitinib was administered at a dose 10 mg twice daily on day 1, followed by 5 mg twice daily on day 2-5. The dosage was reduced up to 5 mg once daily in patients with moderate renal impairment or moderate hepatic impairment.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

I.M. Sechenov First Moscow State Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sergey Moiseev, MD

Role: PRINCIPAL_INVESTIGATOR

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Locations

Sechenov First Moscow State Medical University (Sechenov University) - University Clinical Hospital

Moscow, , Russia

Countries

Russia

Other Identifiers

107892

Identifier Type: -

Identifier Source: org_study_id