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

COVID-19 Clinical Trial

— TOFA-COV-2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04750317
• Other study ID #: 107892
• Status: Completed
• Phase: Phase 2
• Start date: May 11, 2020
• Est. completion date: September 1, 2020

Study information

• Verified date: February 2021
• Source: I.M. Sechenov First Moscow State Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 414
• Est. completion date: September 1, 2020
• Est. primary completion date: August 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• Pneumonia

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Russian Federation	Sechenov First Moscow State Medical University (Sechenov University) - University Clinical Hospital	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
I.M. Sechenov First Moscow State Medical University

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Death	Death registered by medical personnel during in-hospital stay	Within 28 days from admission
Primary	Mechanical ventilation	Initiation of mechanical ventilation during in-hospital stay in patients who did not require ventilation on admission	Within 28 days from admission