Toclizumam Versus Dexamethasone in Severe Covid-19 Cases

randomized controlled trial comparing survival benefit of Tocilizumab therapy with dexamethasone in patients with severe COVID 19

Study Overview

• Status: Completed
• Conditions: Pneumonia, Viral
• Intervention / Treatment: Drug: Tocilizumab; Drug: Dexamethasone

Detailed Description

The current study takes place in the ICU of ESNA hospital, the first COVID-19 quarantine hospital in Egypt, located in Upper Egypt, Luxor governorate during the period from March 2020 to June 2020.

The diagnosis of COVID-19 was made with a positive RT-PCR assay performed on a nasal swab. We have collected data on patients' demographics, comorbidities, symptoms, oxygen support, the ratio of partial pressure of arterial oxygen over the fraction of inspired oxygen (PaO2/FiO2 ratio), laboratory values (complete blood count, CRP, D-Dimer, ferritin, AST, ALT), diagnostic workup, therapies, complications, and outcomes.

Patients were given conventional treatment for COVID-19, including, hydroxychloroquine with a loading dose of 400 mg twice daily followed by 200 mg per day twice daily for additional five days and azithromycin 500 mg per day for five days unless contraindicated. An electrocardiogram was obtained for each patient to check the corrected QT interval at baseline.

In addition to conventional treatment, patients were randomly assigned to either dexamethasone group or tocilizumab (TCZ) group according to random tables.

Eligibility for study included patients with significant deterioration in respiratory clinical status with respiratory rate > 30 cycle/minute, Bilateral CT infiltration > 30%, PaO2/FiO2 ratio <150 or saturation <90 on >6L/min, Two positive laboratory tests of: (CRP>100 g/dL, lymphocytes<600 /mm3, D dimer>L, Ferritin >500).Interleukin 6 levels were not part of the criteria because it did not necessarily result in an actionable time frame.

Pediatric patients < 18 years old, patients with an active bacterial or fungal infection, and patients who were not requiring supplemental oxygen were excluded from the study.

No sample-size calculations were performed. The endpoint was time to failure, defined as death, within 14 days from ICU admission. Patients with a very early death reduced the risk that the treatment choice was motivated by the patient's disease course. Therefore, day 3 from hospital admission was set as a landmark time point: those who died, before the 3rd day of ICU admission, were excluded.

Treatment groups: Dexamethasone pulse therapy group:

All patients within this group received pulse Dexamethasone 4 mg/kg/day in an infusion form for the 3rd day, followed by a maintenance dose of 8 mg/day for 10 days with a subsequent withdrawal.

Tocilizumab group: Patients within this group received TCZ, 4 mg/kg/dose in 100 ccs normal saline over one hour. The same dose was repeated after 24h if there is no improvement in clinical assessment, corticosteroids (Solu-Medrol 40 mg for 5 days then 20 mg for 5 days) was added.

Data was collected at day one of treatment initialization, except for (PaO2/FiO2 ratio), which is also collected after 2 days from the end of the treatment and overall mortality within 14 days.

All patients provided informed consent for treatment with off label agents according to the local protocol approved by Hospital Authorities, for data collection and for participation in the study. The study was carried out in accordance with the principles of the Declaration of Helsinki and approved by the Regional Ethics Committee, Qena faculty of medicine, South-Vally University.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Qinā, Egypt, 83523
    • Qena faculty medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• respiratory rate > 30 cycle/minute, Bilateral CT infiltration > 30%, PaO2/FiO2 ratio <150 or saturation <90 on >6L/min, Two positive laboratory tests of: (CRP>100 g/dL, lymphocytes<600 /mm3, D dimer>L, Ferritin >500)

Exclusion Criteria:

• Pediatric patients < 18 years old, patients with active bacterial or fungal infection and patients who were not requiring supplemental oxygen

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tocilizumab	Drug: Tocilizumab; Tocilizumab therapy; Other Names: TCZ
Active Comparator: Dexamethasone; Dexamethasone therapy	Drug: Dexamethasone; dexamethsone pulse therapy; Other Names: dexamethsone pulse therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of participants with Overall Survival at 14 days	survival 14 days from admission date	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fio2/Pao2	Change in Fio2/Pao2	2 days

Collaborators and Investigators

• Sponsor: South Valley University
• Investigators: Principal Investigator: Alaa R rashad, MD, South Valley University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2020
• Primary Completion (Actual): July 1, 2020
• Study Completion (Actual): August 5, 2020

Study Registration Dates

• First Submitted: August 17, 2020
• First Submitted That Met QC Criteria: August 17, 2020
• First Posted (Actual): August 19, 2020

Study Record Updates

• Last Update Posted (Actual): August 25, 2020
• Last Update Submitted That Met QC Criteria: August 21, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: COVID19; Tocilizumab; dexamethsone
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; COVID-19; Pneumonia, Viral; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Dexamethasone
• Other Study ID Numbers: SouthVU

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No