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

Completed

• Conditions: COVID-19; Mild to Moderate
• Interventions: Drug: Tocilizumab Injection; Drug: Baricitinib Oral Tablet; Drug: Netakimab; Other: Standard of care therapy

• Registration Number: NCT05302947
• Lead Sponsor: Pirogov Russian National Research Medical University

Brief Summary

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.

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 Timeline

• Study Start: 2020-02-01
• Primary Completion: 2020-08-31
• Study Completion: 2021-06-30
• Status Verified: 2022-03
• Study First Submitted: 2022-03-29
• Study First Submitted QC: 2022-03-29
• Study First Posted: 2022-03-31
• Last Update Submitted: 2022-03-31
• Last Update Posted: 2022-04-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 154

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Tocilizumab	Tocilizumab Injection	group included patients received Tocilizumab in addition to standard of care therapy
Baricitinib	Baricitinib Oral Tablet	group included patients received Baricitinib in addition to standard of care therapy
Netakimab	Netakimab	group included patients received Netakimab in addition to standard of care therapy
Control	Standard of care therapy	group included patients received only standard of care therapy at the time of hospital admission according to the corresponding COVID-19 Russian guidelines 2020.

Primary Outcome Measures

Name	Time	Method
Changing in the level of C-reactive protein	5 days	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

Secondary Outcome Measures

Name	Time	Method
Changing in the level of Lactate dehydrogenase	5 days	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.
Assessment of the absolute lymphocyte count in dynamic	5 days	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.
Changing of the National Early Warning Score2	5 days	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.
Assessment of the absolute neutrophil count in dynamic	5 days	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.
Assessment of the neutrophil-to-lymphocyte ratio	5 days	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)

Trial Locations

Locations (2)

City Clinical Hospital No. 52 of the Department of Health of the City of Moscow; 🇷🇺 Moscow, Russian Federation

Pirogov Russian National Research Medical University; 🇷🇺 Moscow, Russian Federation