TOCILIZUMAB - An Option for Patients With COVID-19 Associated Cytokine Release Syndrome; A Single Center Experience

Phase 4

Completed

• Conditions: Covid19
• Interventions: Drug: Tocilizumab

• Registration Number: NCT04730323
• Lead Sponsor: FMH College of Medicine and Dentistry

Brief Summary

Investigators conducted this study to see the effectiveness of Tocilizumab in COVID-19 participants who were in cytokine release syndrome and there was also a control group who received steroids(RECOVERY TRIAL wasn't published or available at that time) this study was conducted in the early days of 1st wave of COVID in our country Pakistan so it was need of the day to develop some national guidelines on the basis of multiple studies' results from Pakistan.

Detailed Description

Objectives: To analyze the effectiveness of Tocilizumab in moderate to severe Covid-19 participants on the basis of predefined assessment criteria.

Study Settings: Single center, Fatima Memorial Hospital, Lahore.

Study Design: Quasi experimental.

Duration of Study: From 12th May, 2020 to 12th July, 2020.

Participants \& Methods: Sample size and technique: Sample size was 93; 33 participants were kept in experimental group, given Tocilizumab, 8mg/kg intravenously or 162 mg subcutaneously and rest of the 60 participants were given corticosteroids, methylprednisolone 80 mg/day. Consecutive sampling.

Failure of therapy was labeled when participants were intubated or died, and the endpoints were failure-free survival which was the primary endpoint and overall survival secondary at the time of discharge.

Study Timeline

• Study Start: 2020-05-12
• Primary Completion: 2020-06-12
• Study Completion: 2020-06-12
• Status Verified: 2021-01
• Study First Submitted: 2021-01-26
• Study First Submitted QC: 2021-01-28
• Last Update Submitted: 2021-01-28
• Study First Posted: 2021-01-29
• Last Update Posted: 2021-01-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 93

Inclusion Criteria

• All patients diagnosed with COVID-19 infection with positive reverse transcriptase RT-PCR test, willing to participate in this study or PCR negative patients with clinically COVID-19 Pneumonia in cytokine storm as evidenced by raised inflammatory markers with typical radiological changes

  • Patients of both genders were included

  • Patients having an age of > 65 years with proven Cardiomyopathy, Coronary artery disease, chronic lung disease, Immunosuppressed or organ transplant End-stage renal disease on history & examination and medical records and having any 1 out of 4 Fever 0f

  • ≥39 C

  • Hypotension or drop in mean arterial pressure of > 10mmHg

  • Progressive Hypoxemia requiring > 5 liters of oxygen

  • Sustained Respiratory rate >30/min with any 2 laboratory parameters out of 3 are present D-dimers ≥ 1000 ng/ml C-reactive protein CRP ≥ 100mg/L Ferritin ≥ 600ng/ml

  • Patients having low risk or no comorbidities and having an age of <65 years with having any 3 out of 4 Fever 0f

  • ≥39 C

  • Hypotension or drop in mean arterial pressure of > 10mmHg

  • Progressive Hypoxemia requiring > 5 liters of oxygen

  • Sustained Respiratory rate >30/min With any 2 laboratory parameters out of 3 are present D-dimers ≥ 1000 ng/ml C-reactive protein CRP ≥ 100mg/L Ferritin ≥ 600ng/ml

  • Moderate severe or severe COVID 19 features

    1. Shortness of breath oxygen saturation <93% on room air
    2. Progressive Hypoxemia requiring > 5 liters of oxygen
    3. Respiratory rate >30/min
    4. The partial pressure of arterial oxygen to fraction of inspired oxygen ratio<300
    5. Lung infiltrates on Chest x-ray CXR >50% within 24 to 48 hrs
    6. Respiratory failure

Exclusion Criteria

• Known severe allergic reactions to Tocilizumab or any other monoclonal antibody
  • Pregnancy or breastfeeding
  • Absolute Neutrophil Count(ANC) < 1000
  • Alanine aminotransferase(ALT) or aspartate aminotransferase (AST) > 5 times upper normal limit
  • Platelet count of < 50,000
  • Bowel diverticulitis or bowel perforation
  • Patients having Acute pancreatitis

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tocilizumab Group	Tocilizumab	Tocilizumab administration protocol: Patients received an initial dose calculated as per the body weight (8mg/kg) maximum 800mg/dose) over 1 hour, followed by up to three additional doses if required as per the response after the first dose with 8 hours intervals. Predefined Parameters of disease severity were assessed 12 to 24 hourly. Injection Paracetamol 1g was administered before infusion.
Methylprednisolone (corticosteroid) group	Tocilizumab	Corticosteroid administration protocol: Patients received methylprednisolone 80mg/day in two divided doses as per national/local guidelines and predefined parameters of disease severity were assessed on each day.

Primary Outcome Measures

Name	Time	Method
Decreased Mortality in Participants	30 days	investigators tried to find out that whether there is decreased mortality in expermiental and active Comparator group or not
Hospital & ICU stay in days	14 days	investigators tried to find out that whether there is decreased hospital and ICU stay in experimental group \& active Comparator

Trial Locations

Locations (1)

Fatima Memorial Hospital College of Medicine & Dentistry; 🇵🇰 Lahore, Punjab, Pakistan