Effect of Interleukin 6 Receptor Antagonists in SARS-CoV-2 Patients

Effects of Sarilumab on Interleukin 6 Levels in Critically Ill COVID-19 Patients

1. Investigate the possible effects of interleukin-6 receptor antagonists such as tocilizumab and sarilumab on the levels of IL-6, inflammtory and anti-inflammtory markers and cytokines before and after treatment in critically ill corona virus disease-19 patients.
2. Correlate between IL-6 levels with other inflammatory markers as ferritin and C-reactive protein.
3. investigate the possible changes on the levels of other inflammatory, anti-inflammatory markers and cytokines such as IL-10 and IP-10, before and after treatment.

Study Overview

• Status: Completed
• Conditions: Corona Virus Infection
• Intervention / Treatment: Diagnostic test: ELISA

Detailed Description

An outbreak of a mutated respiratory virus that belongs to the Coronavirus family was reported in mid-December 2019, in Wuhan, China. The virus was named as severe acute respiratory syndrome coronavirus (SARS-CoV-2) and the disease was named as coronavirus disease-19 (COVID-19) by the WHO. The infection spread pandemically and by the end of October 2021,the number of confirmed cases of COVID-19 reached 244,897,472, including 4,970,435 deaths, reported by WHO. Viral genome was sequenced and published by public health information on 10th of January. COVID-19 uses the same cell entry receptor {Angiotensin converting enzyme II} (ACE2) as SARS-CoV . Recent studies have shown that IL-6 level increased in severe cases of COVID-19. IL-6 is one of the major pro-inflammatory factors that contribute to the formation of cytokine storm.Therefore, the IL-6 monoclonal antibody (mAb) directed COVID-19 therapy has been used in clinical trial in China. The main conclusion they reached was that the treatment with the IL-6 receptor antagonists ( tocilizumab (TCZ), sarilumab, sirukumab, olamkicept and levilimab) improved outcomes, including survival. TCZ is a humanized antibody that blocks both soluble and membrane-bound forms of IL-6 receptor. Sarilumab is a fully human antibody against the IL-6 receptor that binds to both soluble and membrane-bound IL-6 receptors and has the approval of the food and drug administration (FDA) for rheumatoid arthritis (RA) treatment. Additionally, these drugs have been considered for off-label use in the treatment of COVID-19.

• Study Type: Observational
• Enrollment (Actual): 96

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt, 71515
    • AssiutU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

samples will be collected over a duration of one year

Description

Inclusion Criteria:

• must be critically ill coronavirus disease-19

Exclusion Criteria:

• patients receiving corticosteroids
• pregnancy
• active TB
• bacterial infection
• fungal infection
• co-infection with other hepatitis viruses.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
critically ill COVID-19 patients in ICU; critically ill COVID-19 patients who are recommended to receive IL-6R antagonist as tocilizumab at the dosage of 8 mg/kg with a second dose 12 hours after the first dosage, or sarilumab at the dosage of 200 mg subcutaneously or 200 to 800 mg intravenously.	Diagnostic test: ELISA; collection of blood samples from critically ill COVID-19 patients, then serum samples are collected after centrifugation measuring IL-6, IL-10 and IP-10 by ELISA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
interleukin-6 levels	Measuring the levels of interleukin-6 in serum of patients.	during one year
interleukin-10 levels	measuring the levels of interleukin-10 in serum of patients before and after treatment	during one year
inflammatory markers	measuring the levels of some inflammatory markers in serum patients	during one year
interferon gamma inducible protein-10 levels	measuring the levels of IP-10 in serum of patients before and after treatment	during one year
anti-inflammatory markers	measuring the levels of some anti-inflammatory markers in serum of patients before and after treatment	during one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
survival	Calculation of the possible correlation between the variation in interleukin-6 levels and different clinical and laboratory parameters including patient's survival and hospital stay.	during one year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of ventilatory support	Change in respiratory functions with no need for ventilatory support	during one year

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Principal Investigator: mohammad gamal abalrahman, lecturer, Assiut university, Egypt

Publications and helpful links

General Publications

• Li Q, Guan X, Wu P, Wang X, Zhou L, Tong Y, Ren R, Leung KSM, Lau EHY, Wong JY, Xing X, Xiang N, Wu Y, Li C, Chen Q, Li D, Liu T, Zhao J, Liu M, Tu W, Chen C, Jin L, Yang R, Wang Q, Zhou S, Wang R, Liu H, Luo Y, Liu Y, Shao G, Li H, Tao Z, Yang Y, Deng Z, Liu B, Ma Z, Zhang Y, Shi G, Lam TTY, Wu JT, Gao GF, Cowling BJ, Yang B, Leung GM, Feng Z. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia. N Engl J Med. 2020 Mar 26;382(13):1199-1207. doi: 10.1056/NEJMoa2001316. Epub 2020 Jan 29.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Actual): July 20, 2023
• Study Completion (Actual): July 24, 2023

Study Registration Dates

• First Submitted: April 22, 2022
• First Submitted That Met QC Criteria: May 7, 2022
• First Posted (Actual): May 10, 2022

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 24, 2023
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: sarilumab; interleukin-6 receptor antagonists; Corona virus disease; interferon gamma inducible protein-10
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Coronavirus Infections
• Other Study ID Numbers: interleukin6 levels

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