Anti-IL6 and Corticosteroid Monotherapy vs Combination in COVID-19

Clinical Outcome of Anti-IL6 and Corticosteroid Monotherapy vs Combination in COVID-19 Cytokine Release Syndrome

The cytokine storms mediated by over production of proinflammatory cytokines have been observed in a large population of critically ill patients infected with COVID-19. Patients diagnosed with cytokine storms progress to cardiovascular collapse, multiple organ dysfunction and death rapidly. Therefore, early identification, treatment and prevention of the cytokine storms are of crucial importance for the patients. Immuomedulator such as interleukin-6 (IL-6) antagonist, emerged as an alternative treatment for COVID-19 patients with a risk of cytokine storms recently. In this study, we aimed to evaluate the safety and efficacy of anti-IL6 alone vs anti-IL6 corticosteroid combination in patients with COVID-19 pneumonia

Study Overview

• Status: Unknown
• Conditions: Critical Illness; Corona Virus Infection; Cytokine Release Syndrome
• Intervention / Treatment: Drug: Interleukin 6 (IL6) Antagonist; Drug: Interleukin 6 (IL6) Antagonist and corticosteroids; Drug: corticosteroid alone

Detailed Description

This study will provide further insight whether anti-IL6 alone provide same efficacy and clinical outcome with reasonable side effects profile compared to anti-IL6 + corticosteroid and might serve as a corticosteroid sparing agents in COVID-19 patient with cytokine storms. Data elements will be retrieved from VIRUS registry which is a prospective, non-interventional, multi-center, multi-national observational cross sectional study

• Study Type: Observational
• Enrollment (Anticipated): 860

Contacts and Locations

Study Locations

• Saudi Arabia
  • Riyadh, Saudi Arabia
    • Recruiting
    • King Faisal Specialist Hospital and Research Center
    • Contact: Abeer Omar; Email: ORA@kfshrc.edu.sa
    • Principal Investigator: Marwa Amer, PharmD, BCPS,BCCCP
    • Principal Investigator: Mohammed Bawazeer, MD, FRCSC, FACS
    • Sub-Investigator: Eiad Kseibi, MD
    • Sub-Investigator: Talal Dahhan, MD
    • Sub-Investigator: Abid Butt, MD
    • Sub-Investigator: Syed Moazzum Khurshid, MD
    • Sub-Investigator: Muath Rabee, MD
    • Sub-Investigator: Mohammed Abujazar, MD
    • Sub-Investigator: Razan Alghunaim, PharmD
    • Sub-Investigator: Maal Abualkhair, MD
    • Sub-Investigator: Abeer AlFirm, Associate RC Data Manager

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Data elements will be retrieved from Viral Infection and Respiratory Illness Universal Study: COVID-19 (VIRUS registry ClinicalTrials.gov Identifier: NCT04323787) which is a prospective, non-interventional, multi-center, multi-national observational cross sectional study.

Description

Inclusion Criteria:

1. Adult Critically ill patients
2. COVID-19 PCR positive
3. Presence of clinical and radiological signs of progressive disease, and laboratory evidence indicative of risk for cytokine storm complications.
4. Received anti-IL6 or corticosteroids as part of COVID-19 treatment

Exclusion Criteria:

1. Non COVID-19 related admissions
2. Repeated Admission to ICUs/Hospital
3. Patient did not receive anti-IL6 or corticosteroids

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Experimental; anti-IL-6 drugs (tocilizumab and siltuximab)	Drug: Interleukin 6 (IL6) Antagonist; anti-IL6 alone; Other Names: Siltuximab; Tocilizumab
Active Comparator 1; Anti-IL-6 drugs (tocilizumab and siltuximab) and corticosteroids combination	Drug: Interleukin 6 (IL6) Antagonist and corticosteroids; anti-IL6 + corticosteroid combination
Active Comparator 2; corticosteroids alone	Drug: corticosteroid alone; dexamethasone, hydrocortisone, methylprednisolone, prednisone. All steroids " other than dexamethasone" will be converted to dexamethasone equivalent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ventilator-Free Days	The median ventilator-free days will be calculated as calendar days with no ventilator support to day 28 . Participants who die before day 28 are assigned zero free days.	Up to Day 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Median duration of ventilation	From Intubation to extubation date and off Mechanical Ventilation or until ICU discharge, death, or 28 days whichever occurs first.	Up to Day 28
Median change in the PaO2/FiO2	Ratio of arterial oxygen partial pressure (PaO2 in mmHg) to fractional inspired oxygen (FiO2)	Up to Day 28
Vasopressor-Free days	The median vasopressor-free days will be calculated as calendar days with no vasopressor support to day 28. Participants who die before day 28 are assigned zero free days.	Up to Day 28
Duration of ICU Stay	To compare ICU LOS	Up to 28 days
Duration of Hospital Stay	To compare hospital LOS	Up to 28 days
Mortality Rate	Death that occurs during 28 days	Up to Day 28
Percentage of participants with adverse events [transaminitis, hyperglycemia]	adverse events that occurs during 28 days	Up to 28 days
Concentration of Ferritin, IL6, D dimer, fibrinogen, C-reactive protein (CRP), Lactate dehydrogenase (LDH) and absolute lymphocyte count and their correlation with the effectiveness of the treatment	Concentration of inflammatory markers	Up to 28 days
Rate of superinfection (bacterial, viral, invasive fungal infections)		Up to 28 days
Time to the first COVID 19 test negative		Up to 28 days

Collaborators and Investigators

• Sponsor: King Faisal Specialist Hospital & Research Center
• Collaborators: Society of Critical Care Medicine
• Investigators: Principal Investigator: Marwa Amer, PharmD,BCPS, BCCCP, King Faisal Specialist Hospital and Research Center- Riyadh; Principal Investigator: Mohammed Bawazeer, MD,FRCSC,FACS, King Faisal Specialist Hospital and Research Center- Riyadh

Publications and helpful links

General Publications

• Walkey AJ, Kumar VK, Harhay MO, Bolesta S, Bansal V, Gajic O, Kashyap R. The Viral Infection and Respiratory Illness Universal Study (VIRUS): An International Registry of Coronavirus 2019-Related Critical Illness. Crit Care Explor. 2020 Apr 29;2(4):e0113. doi: 10.1097/CCE.0000000000000113. eCollection 2020 Apr.
• Amer M, Kamel AM, Bawazeer M, Maghrabi K, Butt A, Dahhan T, Kseibi E, Khurshid SM, Abujazar M, Alghunaim R, Rabee M, Abualkhair M, Al-Janoubi A, AlFirm AT, Gajic O, Walkey AJ, Mosier JM, Zabolotskikh IB, Gavidia OY, Teruel SY, Bernstein MA, Boman K, Kumar VK, Bansal V, Kashyap R; Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study (VIRUS): COVID-19 Registry Investigator Group. Clinical characteristics and outcomes of critically ill mechanically ventilated COVID-19 patients receiving interleukin-6 receptor antagonists and corticosteroid therapy: a preliminary report from a multinational registry. Eur J Med Res. 2021 Oct 2;26(1):117. doi: 10.1186/s40001-021-00591-x.

Study record dates

Study Major Dates

• Study Start (Actual): July 22, 2020
• Primary Completion (Anticipated): July 22, 2021
• Study Completion (Anticipated): July 22, 2021

Study Registration Dates

• First Submitted: July 22, 2020
• First Submitted That Met QC Criteria: July 22, 2020
• First Posted (Actual): July 24, 2020

Study Record Updates

• Last Update Posted (Actual): March 8, 2021
• Last Update Submitted That Met QC Criteria: March 4, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Disease Attributes; Disease; Shock; Coronavirus Infections; Syndrome; Critical Illness; Cytokine Release Syndrome; Antineoplastic Agents; Siltuximab
• Other Study ID Numbers: RAC # 2201053

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No