Tocilizumab in COVID-19 Lahore General Hospital

SARS-CoV Infection Clinical Trial

— TC19LGH  

Official title:

Tocilizumab: A Therapeutic Cache Against the Treatment of Severe Cases of COVID-19

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04560205
• Other study ID #: LGH001
• Status: Recruiting
• Phase: Phase 1
• Start date: May 1, 2020
• Est. completion date: December 30, 2020

Study information

• Verified date: December 2020
• Source: Lahore General Hospital
• Contact: Muhammad Irfan Malik
• Phone: 03334367220
• Email: drmirfanmalik[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 30, 2020
• Est. primary completion date: December 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Coronavirus Infections
• SARS-CoV Infection
• Severe Acute Respiratory Syndrome

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Pakistan	Lahore General Hospital	Lahore	Punjab

Sponsors (1)

Lead Sponsor	Collaborator
Lahore General Hospital

Country where clinical trial is conducted

Pakistan, 

References & Publications (5)

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. — View Citation

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. Review. — View Citation

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. — View Citation

Ramos-Casals M, Brito-Zerón P, López-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. Review. Erratum in: Lancet. 2014 Apr 26;383(9927):1464. — View Citation

Wichmann D, Sperhake JP, Lütgehetmann M, Steurer S, Edler C, Heinemann A, Heinrich F, Mushumba H, Kniep I, Schröder 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, Püschel 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical response after administration	Clinical improvement of COVID-19 patients by Tocillzumab The number of intubated patients. The number of patients with death.	10 days
Secondary	Clinical response to treatment	Overall survival of COVID-19 patients after drug administration.	15 days
Secondary	Duration of hospitalization	Number of days of hospital admission either in ICU or HDUs till date of discharge	15 days
Secondary	Clinical outcome of the treatment	Mortality rate	15 days
Secondary	Supplemental Oxygen Requirement from Baseline	Duration of increased supplemental oxygen requirement from baseline	15 days