The Use of Tocilizumab in the Management of Patients Who Have Severe COVID-19 With Suspected Pulmonary Hyperinflammation

Title: The use of Tocilizumab in the management of patients who have severe COVID-19 with suspected pulmonary hyperinflammation.

This is a study designed to assess the therapeutic value of intravenous tocilizumab administered as single 8mg/Kg dose in patients affected by SARS-CoV2 infection with a pulmonary manifestation causing hypoxia. Aim of the study is to test the hypothesis that anti-IL6 treatment can be effective in reducing the virus-induced cytokine storm, blocking deterioration of lung function or even promoting a rapid improvement of clinical conditions, preventing tracheal intubation and/or death.

This drug will be administered to those patients entering the ICU with severe acute respiratory failure COVID-19 disease. The endpoints are death and duration of hospitalization. The patients will be assessed with surrogate markers determining the level of the cytokine storm.

Study Overview

• Status: Unknown
• Conditions: Covid19 Pneumonia
• Intervention / Treatment: Drug: Tocilizumab

Detailed Description

Study design This is a multicenter, two arms, 2:1 (treatment: control) open-label randomized control study with a drug approved for another indication in Israel. All the patients enrolled will be treated with tocilizumab or not. One-month mortality rate is the primary endpoint. One arm will be the study drug anti-IL6R (Tocilizumab (Actmera)) 8 mg/kg given IV during one hour once. The placebo will be a 100 ml saline IV infusion administered along one hour.

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 4

Contacts and Locations

Study Locations

• Israel
  • Ashkelon, Israel
    • Recruiting
    • Barzilai Medical Center
    • Contact: Shlomo Maayan, PROF; Phone Number: 972-5-37678965; Email: shlomomom@bmc.gov.il
  • H̱olon, Israel
    • Recruiting
    • Wolfson Medical Center
    • Contact: Yasmin Meir, Dr.; Phone Number: 972-5-26666194; Email: yasminm@wmc.gov.il
  • Ramat Gan, Israel
    • Recruiting
    • Sheba Medical Center
    • Contact: Galia Rahav, Prof.; Phone Number: 972-5-526666190; Email: galia.rahav@sheba.health.gov.il
  • Please Select:
    • Jerusalem, Please Select:, Israel, 91120
      • Recruiting
      • Hadassah Medical Orginisation
      • Contact: Eithan Galun, Prof.; Phone Number: 972-2-6777762; Email: eithang@hadassah.org.il

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:

1. Any gender
2. Age 18 and older
3. Informed consent for participation in the study
4. Virological diagnosis of Sars-CoV2 infection (PCR)
5. Acute respiratory failure
6. Radiographic pneumonia, defined as any/ changing new lung infiltrate
7. Patient breathing spontaneously, required more than 50% oxygen and MEWS score > 7.
8. If intubated, intubated less than 24 hours with PaO2/Fio2 ratio ≤ 200 and PEEP ≥ 5 cm H2O.

Exclusion Criteria:

1. Known hypersensitivity to tocilizumab or its excipients
2. Patient with a life expectancy of less than 6 months.
3. Known active infections or other clinical condition that contra-indicate tocilizumab and cannot be treated or solved according to the judgement of the clinician.
4. Neutrophils <500 / mmc
5. Platelets <40.000 / mmc

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Tocilizumab treatment group; Treatment: intravenous administration of monoclonal anti body anti- IL6R. The dose is 8 mg/kg up to total dose of 800 mg.	Drug: Tocilizumab; The placebo treatment arm will include 100 ml of normal saline administered along 60 min; Other Names: Placebo
PLACEBO_COMPARATOR: Placebo group; Placebo. intravenous administration of 100 ml of normal saline.	Drug: Tocilizumab; The placebo treatment arm will include 100 ml of normal saline administered along 60 min; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	One-month mortality rate .	One-month

Collaborators and Investigators

• Sponsor: Hadassah Medical Organization
• Collaborators: Sheba Medical Center; Wolfson Medical Center
• Investigators: Study Chair: Juli Benbenisty, MPH, Hadassah Medical Organization

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 8, 2020
• Primary Completion (ACTUAL): April 29, 2020
• Study Completion (ANTICIPATED): May 8, 2021

Study Registration Dates

• First Submitted: April 23, 2020
• First Submitted That Met QC Criteria: May 5, 2020
• First Posted (ACTUAL): May 6, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 6, 2020
• Last Update Submitted That Met QC Criteria: May 5, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: SARS-CoV-2; IL-6; Cytokine storm
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: 0224-20-HMO-CTIL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No