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

COVID-19 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05302947
• Other study ID #: BaToNe-COV-2
• Secondary ID: 075-15-2020-807
• Status: Completed
• Start date: February 1, 2020
• Est. completion date: June 30, 2021

Study information

• Verified date: March 2022
• Source: Pirogov Russian National Research Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: June 30, 2021
• Est. primary completion date: August 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19
• Mild to Moderate

Intervention

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
• Tocilizumab Injection
Tocilizumab was administered by a single intravenous dose of 400 mg
• Netakimab
Netakimab was administered by a single subcutaneous injection of 120 mg

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

Locations

Country	Name	City	State
Russian Federation	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

Sponsors (2)

Lead Sponsor	Collaborator
Pirogov Russian National Research Medical University	City Clinical Hospital No.52 of Moscow Healthcare Department

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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