Clinical trial NCT05302947: COVID-19 Study at the Russian Clinical and Research Center of Gerontology of the Pirogov RNRMU
Official title: Tocilizumab, Netakimab, and Baricitinib Versus Standard of Care Therapy in Patients With Mild to Moderate COVID-19 - a Retrospective Observational Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: COVID-19
Mild to Moderate
Keywords: tocilizumab
baricitinib
netakimab
anti-IL-17
c-reactive protein
lactic dehydrogenase
neutrophil-to-lymphocyte ratio
Lead sponsor: Pirogov Russian National Research Medical University
Sponsor class: OTHER
Collaborators: name: City Clinical Hospital No.52 of Moscow Healthcare Department
First posted: 2022-03-31
Enrollment: 154
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changing in the level of C-reactive protein
timeFrame: 5 days
Secondary outcomes:
measure: Changing in the level of Lactate dehydrogenase
timeFrame: 5 days
measure: Assessment of the absolute lymphocyte count in dynamic
timeFrame: 5 days
measure: Assessment of the absolute neutrophil count in dynamic
timeFrame: 5 days
measure: Assessment of the neutrophil-to-lymphocyte ratio
timeFrame: 5 days
measure: Changing of the National Early Warning Score2
timeFrame: 5 days
Other outcomes:
measure: Hospital discharge day and mortality data
timeFrame: 21 days
Locations:
city: Moscow
country: Russian Federation
facility: City Clinical Hospital No. 52 of the Department of Health of the City of Moscow
city: Moscow
country: Russian Federation
facility: Pirogov Russian National Research Medical University
Study officials:
affiliation: City Clinical Hospital No.52 of Moscow Healthcare Department
name: Zinaida Yu Mutovina, MD-PhD
role: PRINCIPAL_INVESTIGATOR
References: