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)
Latest Information Update: 19 Jun 2023
At a glance
- Drugs Tocilizumab (Primary)
- Indications COVID 2019 infections; COVID-19 pneumonia; SARS-CoV-2 acute respiratory disease
- Focus Therapeutic Use
- Acronyms CORON-ACT
- 12 Oct 2020 Status changed from recruiting to discontinued as it was not possible to recruit the planned number of patients during the planned study period and "Dexamethason" was included in the standard of care for the study population during the courseof the study and inclusion criteria could no longer be met.
- 22 Apr 2020 Status changed from not yet recruiting to recruiting.
- 07 Apr 2020 New trial record
Most Recent Events
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.
Comments
According to ClinicalTrials.gov, this study has been terminated as it was not possible to recruit the planned number of patients during the planned study period and "Dexamethason" was included in the standard of care for the study population during the courseof the study and inclusion criteria could no longer be met.
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 | - |
COVID-19 pneumonia | treatment | - |
SARS-CoV-2 acute respiratory disease | treatment | - |
Biomarker
NCT Number | Biomarker Name | Biomarker Function |
---|---|---|
NCT04335071 | C-reactive protein (CRP) | Eligibility Criteria |
Subjects
- Subject Type patients
-
Number
Planned: 100
Actual: 5
- 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
Actual : 27 Sep 2020
-
End Dates
Planned : 01 Oct 2020
Actual : 27 Sep 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
|
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|
Centres
Centre Name | Location | Trial Centre Country |
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- |
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Centre Hospitalier Universitaire Vaudois (CHUV) | Lausanne | Switzerland |
Ospedale Regionale di Lugano (EOC) | Viganello | Switzerland |
Roche Pharma AG |
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University Hospital Bern (Inselspital) | Bern | Switzerland |
University Hospital Inselspital, Berne |
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University Hospital Zurich | Zurich | Switzerland |
Trial History
Event Date | Event Type | Comment |
---|---|---|
19 Jun 2023 | Other trial event | Last checked against the ClinicalTrials.gov record. Updated 19 Jun 2023 |
14 Oct 2020 | Biomarker Update | Biomarkers information updated Updated 04 Nov 2021 |
12 Oct 2020 | Status change - discontinued | Status changed from recruiting to discontinued as it was not possible to recruit the planned number of patients during the planned study period and "Dexamethason" was included in the standard of care for the study population during the courseof the study and inclusion criteria could no longer be met. Updated 16 Oct 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
-
ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2023;.
Available from: URL: http://clinicaltrials.gov
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