Efficacy and Safety of Tofacitinib in Patients With COVID-19 Pneumonia (TOFA-COV-2)

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.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: Tofacitinib

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.

• Study Type: Interventional
• Enrollment (Actual): 414
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 119991
    • Sechenov First Moscow State Medical University (Sechenov University) - University Clinical Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with reduced oxygen saturation ≤93% treated with tofacitinib; Patients with oxygen saturation ≤93% on admission treated with tofacitinib and standard of care treatment	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.
No Intervention: Patients with reduced oxygen saturation treated with SoC; Patients with oxygen saturation ≤93% on admission treated with standard of care only
Experimental: 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	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.
No Intervention: Patients with preserved oxygen saturation >93% on admission treated with SoC; Patients with oxygen saturation >93% on admission treated with standard of care only

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: I.M. Sechenov First Moscow State Medical University
• Investigators: Principal Investigator: Sergey Moiseev, MD, I.M. Sechenov First Moscow State Medical University (Sechenov University)

Study record dates

Study Major Dates

• Study Start (Actual): May 11, 2020
• Primary Completion (Actual): August 1, 2020
• Study Completion (Actual): September 1, 2020

Study Registration Dates

• First Submitted: February 10, 2021
• First Submitted That Met QC Criteria: February 10, 2021
• First Posted (Actual): February 11, 2021

Study Record Updates

• Last Update Posted (Actual): February 15, 2021
• Last Update Submitted That Met QC Criteria: February 11, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Tofacitinib
• Other Study ID Numbers: 107892

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No