Clinical trial NCT04560205: Tocilizumab in COVID-19 Lahore General Hospital
Official title: Tocilizumab: A Therapeutic Cache Against the Treatment of Severe Cases of COVID-19
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: SARS-CoV Infection
Keywords: COVID-19
IL-6 Inhibitor
Lead sponsor: Lahore General Hospital
Sponsor class: OTHER_GOV
First posted: 2020-09-23
Enrollment: 50
Sex: ALL
Minimum age (years): 15
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: quasi-experimental
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Clinical response after administration
timeFrame: 10 days
Secondary outcomes:
measure: Clinical response to treatment
timeFrame: 15 days
measure: Duration of hospitalization
timeFrame: 15 days
measure: Clinical outcome of the treatment
timeFrame: 15 days
measure: Supplemental Oxygen Requirement from Baseline
timeFrame: 15 days
Other outcomes:
Locations:
city: Lahore
country: Pakistan
facility: Lahore General Hospital
state: Punjab
Study officials:
affiliation: Post-Graduate Medical Institute, Lahore General Hospital, Lahore Pakistan
name: Sardar Al-Fareed Zafar
role: STUDY_DIRECTOR
References:
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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.
citation: 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.