COVID-19 Study at the Russian Clinical and Research Center of Gerontology of the Pirogov RNRMU

Tocilizumab, Netakimab, and Baricitinib Versus Standard of Care Therapy in Patients With Mild to Moderate COVID-19 - a Retrospective Observational Study

This is a retrospective observational cohort study. About 1000 hospital charts of adult patients admitted to the hospital with mild-to-moderate COVID-19 from February to August 2020 were analyzed to evaluate the inflammatory markers and clinical outcomes.

The aim of this study was to compare the observed results of targeted immunosuppressive therapy, anti-IL-6R (Tocilizumab), anti-IL-17A (Netakimab), and JAK1/JAK2 inhibitor (Baricitinib), with standard-of-care (SOC) therapy. The investigators hypothesize that, as compared to SOC therapy, all target drugs will demonstrate at least similar beneficial effects.

This observation may additionally support a rational choice for mild-to-moderate COVID-19 treatment strategy, considering the general safety profile and patient-specific limitations.

Study Overview

• Status: Completed
• Conditions: COVID-19; Mild to Moderate
• Intervention / Treatment: Drug: Baricitinib Oral Tablet; Drug: Tocilizumab Injection; Drug: Netakimab; Other: Standard of care therapy

Detailed Description

The clinical data from 154 patients were retrospectively collected according to Inclusion and Exclusion criteria. Finally all patients were divided into four groups depending on therapy: 38 patients who received Baricitinib and SOC; 34 patients who received Tocilizumab and SOC; 48 patients who received Netakimab and SOC and 34 patients who received only SOC.

For all patients the investigators assessed the National Early Warning Score2 (NEWS2), absolute neutrophil count (ANC), absolute lymphocyte count (ALC) and blood neutrophil-to-lymphocyte ratio (NLR) at baseline (0 h, the day of therapy started) and after 72 hours (3 days) and 120 hours (5 days) of therapy. The individual dynamics of c-reactive protein (CRP) and lactate dehydrogenase (LDH) were assessed for patients with known parameters at baseline and 72 h (Δ0-72) or at baseline and 120 h (Δ0-120) to avoid excluding from the analysis patients who lacked CRP or LDH data at one of the time points. The individual dynamics of CRP and LDH for patients for whom the results of sequential measurements were available for all three time points was also assessed separately.

Additionally, the clinical outcomes (death or hospital discharge) and amount of days in hospital after starting therapy were estimate for all 154 patients.

• Study Type: Observational
• Enrollment (Actual): 154

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation
    • Pirogov Russian National Research Medical University
  • Moscow, Russian Federation, 123182
    • City Clinical Hospital No. 52 of the Department of Health of the City of Moscow

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with confirmed COVID-19, hospitalized into the Russian Clinical and Research Center of Gerontology of the Pirogov RNRMU or the City Clinical Hospital No. 52 of the Department of Health of the City of Moscow from 02/01/2020 to 08/31/2020.

Description

Inclusion Criteria:

Subjects who meet all of the following criteria were included in the study:

1. Patients were hospitalized in two Moscow specialized COVID-19 care units from 02/01/2020 to 08/31/2020.
2. Patients had symptoms of acute respiratory infection (fever, muscle pain, cough) and radiologically-defined viral pneumonia as assessed by computed tomography
3. All patients written informed consent for 'off-label' drug use for persons who received tocilizumab, netakimab, or baricitinib

Exclusion Criteria:

Subjects who meet any of the following criteria were excluded from participation in the study:

1. Pregnant women
2. Patients with unknown National Early Warning Score 2 (NEWS2) metric or with NEWS2 > 6 points on the first day of therapy
3. Patients with the plasma level of CRP > 140 mg/l on the first day of therapy
4. Information about the outcome of patients (death or discharge from the hospital) was absent
5. Patients who first time got the investigational drug later than 72 hours after hospitalization
6. Patients who received a combination of the investigational drugs or application was differed to study design
7. Patients with severe hematological, renal, or liver function impairment or evidence of concomitant bacterial infections.

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Baricitinib; group included patients received Baricitinib in addition to standard of care therapy	Drug: Baricitinib Oral Tablet; Baricitinib was administered at a dose of 4 mg once or twice per day for 3-8 days (5 days on average) depending on the individual patients' condition; Other Names: Olumiant
Tocilizumab; group included patients received Tocilizumab in addition to standard of care therapy	Drug: Tocilizumab Injection; Tocilizumab was administered by a single intravenous dose of 400 mg; Other Names: Actemra
Netakimab; group included patients received Netakimab in addition to standard of care therapy	Drug: Netakimab; Netakimab was administered by a single subcutaneous injection of 120 mg; Other Names: Efleira
Control; group included patients received only standard of care therapy at the time of hospital admission according to the corresponding COVID-19 Russian guidelines 2020.	Other: Standard of care therapy; SOC treatment included hydroxychloroquine (400 mg twice on day 1, followed by 200 mg twice per day on days 5-10), azithromycin (500 mg once per day for 5 days), lopinavir-ritonavir (400/100 mg twice per day for 14 days), and low molecular-weight heparin according to personal indicators; Other Names: SOC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changing in the level of C-reactive protein	The level of C-reactive protein (mg/L ) was measured by ELISA on the day of the start of therapy and then after 72 hours and 120 hours	5 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changing in the level of Lactate dehydrogenase	The blood level of lactate dehydrogenase (LDH, U/L) was estimate by enzymatic UV-Kinetic method on the day of the start of therapy and then after 72 hours and 120 hours.	5 days
Assessment of the absolute lymphocyte count in dynamic	The absolute lymphocyte count (ALC) was assessed by using an automatic hematology analyzer on the day of the start of therapy and then after 72 hours and 120 hours.	5 days
Assessment of the absolute neutrophil count in dynamic	The absolute neutrophil count (ANC) was assessed by using an automatic hematology analyzer on the day of the start of therapy and then after 72 hours and 120 hours.	5 days
Assessment of the neutrophil-to-lymphocyte ratio	The mathematical ratio of ANC to ALC were calculated for timepoints 0 ( the day of the start of therapy), 3 (72 hours after the start of the therapy) and 5 (120 hours after the start of the therapy)	5 days
Changing of the National Early Warning Score2	The National Early Warning Score2 (NEWS2) metric based on physiological variables including blood pressure, heart rate, respiratory rate, temperature, oxygen saturation, and level of consciousness and falls on a scale of 0 to 20. NEWS2 value at 0-4 points corresponds to low clinical risk, 5-6 points to medium risk and 7 or more points to high clinical risk. NEWS2 was estimate on the day of the start of therapy and then after 72 hours and 120 hours.	5 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital discharge day and mortality data	The amount of days in the hospital after the start of therapy was estimated for each patients and and analysed as the following groups: less than 4 days in hospital; 5-7 days in hospital; 8-14 days in hospital; more than 15 days in hospital. Outcome (hospital discharge or death) was assessed on the last day of follow-up, the longest period of hospitalisation was 21 days.	21 days

Collaborators and Investigators

• Sponsor: Pirogov Russian National Research Medical University
• Collaborators: City Clinical Hospital No.52 of Moscow Healthcare Department
• Investigators: Principal Investigator: Zinaida Yu Mutovina, MD-PhD, City Clinical Hospital No.52 of Moscow Healthcare Department

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2020
• Primary Completion (Actual): August 31, 2020
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: March 29, 2022
• First Submitted That Met QC Criteria: March 29, 2022
• First Posted (Actual): March 31, 2022

Study Record Updates

• Last Update Posted (Actual): April 8, 2022
• Last Update Submitted That Met QC Criteria: March 31, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: tocilizumab; baricitinib; c-reactive protein; netakimab; neutrophil-to-lymphocyte ratio; anti-IL-17; lactic dehydrogenase
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: BaToNe-COV-2; 075-15-2020-807 (Other Grant/Funding Number: Ministry of Science and Higher Education RF)

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: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes