Clinical trial NCT04377750: The Use of Tocilizumab in the Management of Patients Who Have Severe COVID-19 With Suspected Pulmonary Hyperinflammation
Official title: The Use of Tocilizumab in the Management of Patients Who Have Severe COVID-19 With Suspected Pulmonary Hyperinflammation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Covid19 Pneumonia
Keywords: SARS-CoV-2
Cytokine storm
IL-6
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
Collaborators: name: Sheba Medical Center
name: Wolfson Medical Center
First posted: 2020-05-06
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Survival
timeFrame: One-month
Secondary outcomes:
Other outcomes:
Locations:
city: Jerusalem
country: Israel
facility: Hadassah Medical Orginisation
state: Please Select:
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: H̱olon
country: Israel
facility: Wolfson Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
Study officials:
affiliation: Hadassah Medical Organization
name: Juli Benbenisty, MPH
role: STUDY_CHAIR
References: