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CORON-ACT - a Multicenter, Double-blind, Randomized Controlled Phase II Trial on the Efficacy and Safety of Tocilizumab in the Treatment of Coronavirus Induced Disease (COVID-19)

Trial Profile

CORON-ACT - a Multicenter, Double-blind, Randomized Controlled Phase II Trial on the Efficacy and Safety of Tocilizumab in the Treatment of Coronavirus Induced Disease (COVID-19)

Status: Recruiting
Phase of Trial: Phase II

Latest Information Update: 29 Apr 2020

At a glance

  • Drugs Tocilizumab (Primary)
  • Indications COVID 2019 infections; Severe acute respiratory syndrome
  • Focus Therapeutic Use
  • Acronyms CORON-ACT
  • Most Recent Events

    • 22 Apr 2020 Status changed from not yet recruiting to recruiting.
    • 07 Apr 2020 New trial record

Trial Overview

Purpose

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.

Primary Endpoints

Number of patients with ICU admission

time_frame: 7 days after randomisation

Number of patients with intubation

time_frame: 14 days after randomisation

Number of patients with death

time_frame: 28 days after randomisation

Other Endpoints

Illness severity

description: Assessed by the 8-point WHO scale
time_frame: At days 2, 7, 14, 28 after randomisation

Number of patients with clinical improvement

description: Clinical improvement is defined as a ≥ 2-point improvement in the 8-point WHO scale
time_frame: At days 2, 7, 14, 28 after randomisation

Time to clinical improvement (days)

description: Clinical improvement is defined as a ≥ 2-point improvement in the 8-point WHO scale
time_frame: Up to day 28 after randomisation

Duration of hospitalization (days)

time_frame: Up to day 28 after randomisation

Time to ICU admission (days)

time_frame: Up to day 28 after randomisation

Duration of ICU stay

time_frame: Up to day 28 after randomisation

Time to intubation

time_frame: Up to day 28 after randomisation

Duration of mechanical ventilation (days)

time_frame: Up to day 28 after randomisation

Number of deaths

time_frame: Within 28 days after randomisation

Number of patients with events of special interest

description: Events of special interest are defined as secondary infections, acute kidney failure, hepatic, and cardiac failure
time_frame: Within 28 days after randomisation

Number of patients with SAEs considered by the investigator to be at least probably related to the IMP

time_frame: Within 28 days after randomisation [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -
Severe acute respiratory syndrome treatment -

Subjects

  • Subject Type patients
  • Number

    Planned: 100

  • Sex male & female
  • Age Group 30-80 years; adult; elderly

Patient Inclusion Criteria

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)

Patient Exclusion Criteria

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 - Platelets <50 G/L

Trial Details

Identifiers

Identifier Owner
NCT04335071 ClinicalTrials.gov: US National Institutes of Health
2020-00691 -
2020DR2044 -

Organisations

  • Affiliations Roche Pharma AG

Trial Dates

  • Initiation Dates

    Planned : 01 Apr 2020

    Actual : 26 Apr 2020

  • Primary Completion Dates

    Planned : 01 Oct 2020

  • End Dates

    Planned : 01 Oct 2020

Other Details

  • Design double-blind; multicentre; parallel; prospective; randomised
  • Phase of Trial Phase II
  • Location Switzerland
  • Focus Therapeutic Use

Interventions

Drugs Route Formulation
TocilizumabPrimary Drug Intravenous Infusion

Actemra

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) (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.) Other Name: Actemra

Placebo

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 (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.) Other Name: NaCl 0.9%

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Peter M. Villiger, Prof. Dr. med.
+41 (0)31 632 98 40 peter.villiger@insel.ch
show details
University Hospital Bern (Inselspital) Switzerland
Stephan Reichenbach, Prof. Dr.med.
+41 31 631 56 98 stephan.reichenbach@ispm.unibe.ch
show details
-

Centres

Centre Name Location Trial Centre Country
-
-
-
Centre Hospitalier Universitaire Vaudois (CHUV) Lausanne Switzerland
Ospedale Regionale di Lugano (EOC) Viganello Switzerland
Roche Pharma AG
-
-
University Hospital Bern (Inselspital) Bern Switzerland
University Hospital Inselspital, Berne
-
-
University Hospital Zurich Zurich Switzerland

Trial History

Event Date Event Type Comment
29 Apr 2020 Other trial event Last checked against the ClinicalTrials.gov record. Updated 29 Apr 2020
22 Apr 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 27 Apr 2020
07 Apr 2020 New trial record New trial record Updated 07 Apr 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
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