Tocilizumab in COVID-19 Lahore General Hospital

NCT ID: NCT04560205

Last Updated: 2020-12-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-01
• Study Completion Date: 2020-12-30

Brief Summary

The most accepted description of severe COVID-19 disease is development and over production of pro-inflammatory cytokines. Autopsy studies have been done on COVID-19 patients proved that severe disease is resulted due to deviant host-immune response and cytokine storm. Elevated inflammatory biomarkers like C-Reactive protein (CRP) and pro-inflammatory cytokines shown to be higher in severe disease of COVID-19. Several studies on severe COVID-19 have revealed raised levels of plasma cytokines like IL-6, IL-2, IL-10, Gamma interferon (INF), Tumor necrosis factor Alpha TNF. The Cytokines release syndrome (CRS) is a hyperinflammatory deadly syndrome characterized by release of uncontrolled immune system activation which is responsible for multi-organ failure. It has the main role in ARDS due to SARS-CoV-2 virus which binds to alveolar epithelium and resulting in IL-6 release that is responsible for increase alveolar-epithelium permeability. In many studies it has been observed that IL-6 have played a main role in CRS induction. Previous experiences from hyperinflammatory and cytokine storm syndromes recommends that early involvement of inhibiting CRS is essential to prevent lethal tissue damage and poor clinical outcome. In this scenario the judgement of clinical specialist who are suggesting that evidence of CRS can be cured with glucocorticoids, I/V immunoglobulin and anti-cytokine therapy cannot be ignored.

Detailed Description

This is intervention single-center study, that will be done at Lahore General Hospital in which 95 beds are allocated for COVID-19 patients including ICUs and HDUs. Ethical approval will be obtained from research ethical committee of Lahore General hospital, Lahore. Informed consent will be obtained from all patients who will agree to publish their data in this research. Patient's privacy and obey will be protected with the Helsinki Declaration.

Conditions

SARS-CoV Infection

Keywords

COVID-19; IL-6 Inhibitor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group intervene with Tocilizumab

Review effect of Tocilizumab as clinical trial among hospitalized patients with COVID-19 infection.

Participants with severe disease will receive an intravenous (IV) injection of 8 mg/kg (not to exceed 800 mg) tocilizumab. Specifically, we will test whether tocilizumab is associated with a reduction in multi-organ dysfunction among hospitalized COVID-19 adult patients with elevated inflammatory biomarkers.

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: DRUG

4-8mg/kg with 400mg maximum dose of Tocilizumab will be given in 60 minutes I/V infusion, and dose will be repeated after 12-24 hours according to clinical as well as laboratory parameters.

Customized decision for Tocilizumab usage will be made by attending infectious diseases physician, comfort with Tocilizumab usage, bacterial co-infection and duration of Ventilation.

Interventions

Tocilizumab

4-8mg/kg with 400mg maximum dose of Tocilizumab will be given in 60 minutes I/V infusion, and dose will be repeated after 12-24 hours according to clinical as well as laboratory parameters.

Customized decision for Tocilizumab usage will be made by attending infectious diseases physician, comfort with Tocilizumab usage, bacterial co-infection and duration of Ventilation.

Intervention Type: DRUG

Other Intervention Names

ACTEMRA®

Eligibility Criteria

Inclusion Criteria

• All patients of all ages, males and non-pregnant females who will be diagnosed COVID-19 positive by RT-PCR.
• Patients having classical radiological lesions of COVID-19 on X-ray chest or HRCT chest.
• Patient >55 years of age Or Age <55 with comorbid condition who will be unable to maintain O2 sat > 93% with 5-7 liter of oxygen.
• Or Patient < 55 with no comorbid conditions, who will be unable to maintain O2 sat > 93% with 7-10 liter of oxygen.
• Respiratory rate > 30-35/ min and >50% of radiological involvement of lung with typical lesions.
• Along with > 50% deranged ≥ 2 biochemical markers CRP > 50 mg/l, LDH > 1000U/L, D.Dimer > 1mg/l or 1000 ng/ml, Serum Ferritin > 1000 ng/ml or mcg/l will be included in clinical trial.

Exclusion Criteria

• Patient who will not require supplemental oxygen during hospital stay.
• Patients on Invasive mechanical ventilation (IMV).
• Patients with respiratory rate < 30/mins and whose laboratory findings will not be deranged > 50%.
• Patients with improving radiological findings will be excluded.
• Patients suffering from Active TB
• Herpes zoster
• Multiple sclerosis,
• Allergic to tocilizumab
• Presences of chronic renal failure > 4 stage, GFR < 30ml/min/1.73m2.
• ALT/AST > 5 times than normal values.
• Presences of neutropenia < 500/mm3.
• Platelets count less than 50 ×103 /µl.
• Complicated diverticulitis/ intestinal perforation.
• Immune-suppressive anti- rejection therapy.
• Pregnant women.
• Previous MI/ IHD, IV heart failure.
• Psychiatric patients.

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lahore General Hospital

OTHER_GOV

Sponsor Role: lead

Responsible Party

Dr. M.Irfan Malik

Associate Professor of Pulmonology / Focal Person COVID-19

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sardar Al-Fareed Zafar

Role: STUDY_DIRECTOR

Post-Graduate Medical Institute, Lahore General Hospital, Lahore Pakistan

Locations

Lahore General Hospital

Lahore, Punjab Province, Pakistan

Site Status: RECRUITING

Countries

Pakistan

Central Contacts

Muhammad Irfan Malik

Role: CONTACT

Phone: 03334367220

Email: drmirfanmalik@hotmail.com

Facility Contacts

Muhammad Irfan malik

Role: primary

References

Wichmann D, Sperhake JP, Lutgehetmann M, Steurer S, Edler C, Heinemann A, Heinrich F, Mushumba H, Kniep I, Schroder AS, Burdelski C, de Heer G, Nierhaus A, Frings D, Pfefferle S, Becker H, Bredereke-Wiedling H, de Weerth A, Paschen HR, Sheikhzadeh-Eggers S, Stang A, Schmiedel S, Bokemeyer C, Addo MM, Aepfelbacher M, Puschel K, Kluge S. Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study. Ann Intern Med. 2020 Aug 18;173(4):268-277. doi: 10.7326/M20-2003. Epub 2020 May 6.

Reference Type: BACKGROUND

PMID: 32374815 (View on PubMed)

Ramos-Casals M, Brito-Zeron P, Lopez-Guillermo A, Khamashta MA, Bosch X. Adult haemophagocytic syndrome. Lancet. 2014 Apr 26;383(9927):1503-1516. doi: 10.1016/S0140-6736(13)61048-X. Epub 2013 Nov 27.

Reference Type: BACKGROUND

PMID: 24290661 (View on PubMed)

Radbel J, Narayanan N, Bhatt PJ. Use of Tocilizumab for COVID-19-Induced Cytokine Release Syndrome: A Cautionary Case Report. Chest. 2020 Jul;158(1):e15-e19. doi: 10.1016/j.chest.2020.04.024. Epub 2020 Apr 25.

Reference Type: BACKGROUND

PMID: 32343968 (View on PubMed)

Liu B, Li M, Zhou Z, Guan X, Xiang Y. Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)? J Autoimmun. 2020 Jul;111:102452. doi: 10.1016/j.jaut.2020.102452. Epub 2020 Apr 10.

Reference Type: BACKGROUND

PMID: 32291137 (View on PubMed)

Henderson LA, Canna SW, Schulert GS, Volpi S, Lee PY, Kernan KF, Caricchio R, Mahmud S, Hazen MM, Halyabar O, Hoyt KJ, Han J, Grom AA, Gattorno M, Ravelli A, De Benedetti F, Behrens EM, Cron RQ, Nigrovic PA. On the Alert for Cytokine Storm: Immunopathology in COVID-19. Arthritis Rheumatol. 2020 Jul;72(7):1059-1063. doi: 10.1002/art.41285. Epub 2020 May 10.

Reference Type: BACKGROUND

PMID: 32293098 (View on PubMed)

Other Identifiers

LGH001

Identifier Type: -

Identifier Source: org_study_id