Tocilizumab in COVID-19 Lahore General Hospital

NCT04560205 | Unknown Phase 1 DMC

• 1 other identifier: LGH001
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

SARS-CoV Infection

Keywords

COVID-19; IL-6 Inhibitor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Clinical response to treatment

  15 days

• Duration of hospitalization

  15 days

• Clinical outcome of the treatment

  15 days

• Supplemental Oxygen Requirement from Baseline

  15 days

Study Arms (1)

Group intervene with Tocilizumab

EXPERIMENTAL

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.

Drug: Tocilizumab

Interventions

Tocilizumab 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.

Also known as: ACTEMRA®

Group intervene with Tocilizumab

Eligibility Criteria

• Age: 15 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Lahore General Hospital: lead

Study Sites (1)

Lahore General Hospital

Lahore, Punjab Province, 54500, Pakistan

RECRUITING

Related Publications (5)

• 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.

  PMID: 32374815 BACKGROUND

• 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.

  PMID: 24290661 BACKGROUND

• 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.

  PMID: 32343968 BACKGROUND

• 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.

  PMID: 32291137 BACKGROUND

• 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.

  PMID: 32293098 BACKGROUND

MeSH Terms

Conditions

Severe Acute Respiratory Syndrome; COVID-19

Interventions

tocilizumab

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases

Study Officials

• Sardar Al-Fareed Zafar

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

  STUDY DIRECTOR

Central Study Contacts

Muhammad Irfan Malik

CONTACT

03334367220; drmirfanmalik@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pulmonology / Focal Person COVID-19

Model Details: quasi-experimental

Study Record Dates

• First Submitted: July 11, 2020
• First Posted: September 23, 2020
• Study Start: May 1, 2020
• Primary Completion: December 30, 2020
• Study Completion: December 30, 2020
• Last Updated: December 8, 2020

Record last verified: 2020-12

Locations

PA (1)