SARS-CoV Infection
Conditions
Keywords
COVID-19, IL-6 Inhibitor
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.
Interventions
DRUGTocilizumab
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.
Sponsors
Lahore General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
quasi-experimental
Eligibility
Sex/Gender
ALL
Age
15 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical response after administration | 10 days | Clinical improvement of COVID-19 patients by Tocillzumab The number of intubated patients. The number of patients with death. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical response to treatment | 15 days | Overall survival of COVID-19 patients after drug administration. |
| Duration of hospitalization | 15 days | Number of days of hospital admission either in ICU or HDUs till date of discharge |
| Clinical outcome of the treatment | 15 days | Mortality rate |
| Supplemental Oxygen Requirement from Baseline | 15 days | Duration of increased supplemental oxygen requirement from baseline |
Countries
Pakistan
Contacts
Primary ContactMuhammad Irfan Malik
Outcome results
None listed