Tocilizumab in the Treatment of Coronavirus Induced Disease (COVID-19)

NCT04335071 | Terminated Phase 2 DMC

• 2 other identifiers: 2020-006912020DR2044
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 4

Brief Summary

The mortality rate of the disease caused by the corona virus induced disease (COVID-19) has been estimated to be 3.7% (WHO), which is more than 10-fold higher than the mortality of influenza. Patients with certain risk factors seem to die by an overwhelming reaction of the immune system to the virus, causing a cytokine storm with features of Cytokine-Release Syndrome (CRS) and Macrophage Activation Syndrome (MAS) and resulting in Acute Respiratory Distress Syndrome (ARDS). Several pro-inflammatory cytokines are elevated in the plasma of patients and features of MAS in COVID-19, include elevated levels of ferritin, d-dimer, and low platelets. There is increasing data that cytokine-targeted biological therapies can improve outcomes in CRS or MAS and even in sepsis. Tocilizumab (TCZ), an anti-IL-6R biological therapy, has been approved for the treatment of CRS and is used in patients with MAS. Based on these data, it is hypothesized that TCZ can reduce mortality in patients with severe COVID-19 prone to CRS and ARDS. The overall purpose of this study is to evaluate whether treatment with TCZ reduces the severity and mortality in patients with COVID-19.

Conditions

SARS-CoV-2 Infection

Keywords

Covid-19; Pneumonia; Tocilizumab

Outcome Measures

Primary Outcomes (3)

• Number of patients with ICU admission

  7 days after randomisation

• Number of patients with intubation

  14 days after randomisation

• Number of patients with death

  28 days after randomisation

Secondary Outcomes (8)

• Illness severity

  At days 2, 7, 14, 28 after randomisation

• Number of patients with clinical improvement

  At days 2, 7, 14, 28 after randomisation

• Time to clinical improvement (days)

  Up to day 28 after randomisation

• Duration of hospitalization (days)

  Up to day 28 after randomisation

• Time to ICU admission (days)

  Up to day 28 after randomisation

Other Outcomes (5)

• Number of deaths

  Within 28 days after randomisation

• Number of patients with ICU admission

  Within 28 days after randomisation

• Number of patients with intubation

  Within 28 days after randomisation

Study Arms (2)

Actemra

EXPERIMENTAL

Patients get one dose (= 8 mg/kg bodyweight, max. single dose 800 mg) Actemra® (active ingredient: TCZ) intravenously in 100 mL NaCl 0.9% after confirmation of progressive dyspnoea. Infusion time: 60 min. The procedure is repeated once if no improvement in the 8-point WHO scale is observed.

Drug: Tocilizumab (TCZ)

Placebo

PLACEBO COMPARATOR

The placebo-controlled intervention is one dose (100 mL) NaCl 0.9% intravenously administered after confirmation of progressive dyspnoea. Infusion time: 60 min. The procedure is repeated once if no improvement in the 8-point WHO scale is observed.

Drug: Placebo

Interventions

Tocilizumab (TCZ) DRUG

Patients get one dose (= 8 mg/kg bodyweight, max. single dose 800 mg) Actemra® (active ingredient: TCZ) intravenously in 100 mL NaCl 0.9% after confirmation of progressive dyspnoea. Infusion time: 60 min. The procedure is repeated once if no clinical improvement in the 8-point WHO scale is observed.

Also known as: Actemra

Actemra

Placebo DRUG

The placebo-controlled intervention is one dose (100 mL) NaCl 0.9% intravenously administered after confirmation of progressive dyspnoea. Infusion time: 60 min. The procedure is repeated once if no clinical improvement in the 8-point WHO scale is observed.

Also known as: NaCl 0.9%

Placebo

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• I (first step):
• Admission to hospital
• Male or non-pregnant female, ≥60 years of age or ≥30 years of age plus one or more known risk factors (arterial hypertension, diabetes mellitus, coronary heart disease, heart failure, pre-existing chronic pulmonary disease)
• Confirmed SARS-CoV infection
• Radiographic evidence compatible with Covid-19 pneumonia (X-ray/CT scan, etc.)
• Signed Informed Consent Form
• II (second step; indication for intervention):
• CRP ≥50mg/L plus 3 out of the following 5 criteria need to be fulfilled:
• Respiration Rate ≥25
• SpO2 \<93% (on ambient air)
• PaO2 \<65 mmHg
• Persistent or increasing dyspnoea as defined by a one point increase on the mMRC dyspnoea scale (over 1 hour)
• Persistent or increasing oxygen demand (over 1 hour)

You may not qualify if:

• I (first step):
• Patients \>80 years of age
• Patient included in any other interventional trial
• Indication for imminent or immediate transfer to ICU
• Treatment with TCZ (or other anti-IL-6R treatment) within 4 weeks prior to baseline
• Uncontrolled bacterial superinfection according to investigator
• History of severe allergic reaction to TCZ
• History of diverticulitis requiring antibiotic treatment or history of colon perforation
• History of primary immunodeficiency (e.g. CVID) or progressing malignancy
• History of chronic liver disease (\>Child-Pugh A, or according to investigator)
• II (second step; contraindication for intervention):
• Alanine transaminase/aspartate transaminase (ALT/AST) \>5 times of the upper limit of normal
• Hemoglobin \<80 g/L
• Leukocytes \<2.0 G/L
• Absolute neutrophil count \<1.0 G/L

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Roche Pharma AG: collaborator

Study Sites (4)

University Hospital Bern (Inselspital)

Bern, 3010, Switzerland

Location

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, 1011, Switzerland

Location

Ospedale Regionale di Lugano (EOC)

Viganello, 6962, Switzerland

Location

University Hospital Zurich

Zurich, 8091, Switzerland

Location

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MeSH Terms

Conditions

COVID-19; Pneumonia

Interventions

tocilizumab; Sodium Chloride

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Peter M. Villiger, Prof. Dr. med.

  University Hospital Bern (Inselspital)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All participants and study personnel involved in patient enrolment, treatment, and follow-up will be masked to group assignment until the final report will be completed and a first interpretation of the results has been done.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: A multicenter, double-blind, randomized controlled phase II trial

Study Record Dates

• First Submitted: April 2, 2020
• First Posted: April 6, 2020
• Study Start: April 26, 2020
• Primary Completion: September 27, 2020
• Study Completion: September 27, 2020
• Last Updated: October 14, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

CH (4)