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

Phase 4

• Conditions: Covid19 Pneumonia
• Interventions: Drug: Tocilizumab

• Registration Number: NCT04377750
• Lead Sponsor: Hadassah Medical Organization

Brief Summary

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.

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 Timeline

• Status Verified: 2020-04
• Study Start: 2020-04-08
• Study First Submitted: 2020-04-23
• Primary Completion: 2020-04-29
• Study First Submitted QC: 2020-05-05
• Last Update Submitted: 2020-05-05
• Study First Posted: 2020-05-06
• Last Update Posted: 2020-05-06
• Study Completion: 2021-05-08

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 500

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tocilizumab treatment group	Tocilizumab	Treatment: intravenous administration of monoclonal anti body anti- IL6R. The dose is 8 mg/kg up to total dose of 800 mg.
Placebo group	Tocilizumab	Placebo. intravenous administration of 100 ml of normal saline.

Primary Outcome Measures

Name	Time	Method
Survival	One-month	One-month mortality rate .

Trial Locations

Locations (4)

Hadassah Medical Orginisation; 🇮🇱 Jerusalem, Please Select:, Israel

Barzilai Medical Center; 🇮🇱 Ashkelon, Israel

Wolfson Medical Center; 🇮🇱 H̱olon, Israel

Sheba Medical Center; 🇮🇱 Ramat Gan, Israel