Efficacy and Safety of Tocilizumab in the Treatment of Patients With Respiratory Distress Syndrome and Cytokine Release Syndrome Secondary to COVID-19: a Proof of Concept Study
Latest Information Update: 10 Apr 2022
At a glance
- Drugs Tocilizumab (Primary)
- Indications Adult respiratory distress syndrome; COVID 2019 infections; Cytokine release syndrome
- Focus Proof of concept; Therapeutic Use
- Acronyms TOSCA
- 09 Apr 2020 Status changed from not yet recruiting to recruiting.
- 07 Apr 2020 New trial record
Most Recent Events
Trial Overview
Purpose
This is a prospective observational clinical study and it is aimed at verifying tocilizumab efficacy and safety in patients with COVID-19 complicated by acute distress respiratory syndrome (ARDS) and Cytokine Release Syndrome.
Primary Endpoints
Percentage of patients with complete recovery defined as fever disappearance and return to normal peripheral oxygen saturation values (SpO2) after 14 days from the end of treatment with tocilizumab.
description: Fever normalization criteria: Temperature <36.6 ° C for at least 72 hours; SpO2 normalization criterion: SpO2> 94% for at least 72 hours
time_frame: 14 days
Other Endpoints
Percentage of patients achieving a score <3 on the Brescia-COVID respiratory severity scale (BCRSS) after the last tocilizumab administration.
time_frame: 24 hours
Percentage of patients with partial recovery defined as the disappearance of fever 14 days after the end of treatment with tocilizumab.
description: Fever normalization criteria: Temperature <36.6 ° C for at least 72 hours
time_frame: 14 days
Duration of hospitalization
description: days
time_frame: 14 days
Time to the first negative SARS-CoV-2 negative RT-PCR test
description: days
time_frame: 14 days
Changes from the baseline in the white blood cell count
description: number/microliter
time_frame: 7, 14 days
Changes from the baseline in the lymphocyte populations (cluster of differentiation (CD)3+CD4+, CD3+CD8+, CD19+, Th17)
description: number/microliter
time_frame: 7, 14 days
Changes from the baseline of c-reactive protein (CRP) values
time_frame: 7, 14 days
Changes from the baseline of Ferritin values
time_frame: 7, 14 days
Changes from the baseline of BNP values
time_frame: 7,14 days
Changes from the baseline of CK-MB values
time_frame: 7,14 days
Changes from the baseline of Troponin values
time_frame: 7,14 days
Changes from the baseline of LDH values
time_frame: 7,14 days
Changes from the baseline of myoglobulin values
time_frame: 7,14 days
Changes in myocardial ischemia signs at the electrocardiographic trace (YES or NO)
description: (ST segments elevation or depression, T-wave changes)
time_frame: 7,14 days
Rate of adverse events report during and after tocilizumab
time_frame: 14 days
Mortality (number of Partecipants, cause and timing)
time_frame: 12 weeks
Percentage of patients who develop autoimmune diseases
time_frame: 1 year [1]
Diseases Treated
| Indication | Qualifiers | Patient Segments |
|---|---|---|
| Adult respiratory distress syndrome | treatment | - |
| COVID 2019 infections | treatment | - |
| Cytokine release syndrome | treatment | - |
Biomarker
| NCT Number | Biomarker Name | Biomarker Function |
|---|---|---|
| NCT04332913 | B-lymphocyte antigen CD19 | Outcome Measure |
| BNP | Outcome Measure | |
| C-reactive protein (CRP) | Eligibility Criteria, Outcome Measure | |
| Cardiac Troponin I | Outcome Measure | |
| CD3 gamma chain (CD3G) | Outcome Measure | |
| CKB | Outcome Measure | |
| CKM | Outcome Measure | |
| D-dimer | Eligibility Criteria | |
| Ferritin | Eligibility Criteria, Outcome Measure | |
| Fibrinogen | Eligibility Criteria | |
| Interleukin-6 (IL-6) | Eligibility Criteria | |
| T-Cell differentiation antigen CD8 | Outcome Measure | |
| T-cell receptor CD3-epsilon (CD3e) | Outcome Measure | |
| T-cell receptor T3 delta chain (CD3d) | Outcome Measure | |
| T-cell surface antigen CD4 | Outcome Measure |
Subjects
- Subject Type patients
-
Number
Planned: 30
- Sex male & female
- Age Group ≥ 18 years; adult
Patient Inclusion Criteria
- All gender patients aged ≥ 18 years; - Patients with SARS-CoV-2 infection confirmed by tests (RT-PCR) and pulmonary involvement, hospitalized, at the end of the initial phase of high viral load of COVID-19 (apyretic> 72 hours and / or at least 7 days after onset of symptoms); - Worsening of respiratory exchanges such as to require non-invasive or invasive ventilation support (BCRSS score ≥ 3). - High levels of IL-6 (> 40 pg/mL) or alternatively CRP and/or ferritin and/or D-dimer and/or fibrinogen values higher than the reference values or rapidly increasing; - Signature of informed consent.
Patient Exclusion Criteria
- Alanine aminotransferase and/or Aspartate aminotransferase (ALT / AST) > 5 times compared to normal laboratory values. - Presence of a chronic renal failure ≥ 4 stage (glomerular filtrate values <30 ml/min/1.73 m2). - Presence of neutropenia (neutrophils count < 500 / mm3). - Platelet count less than 50 x 103/μL. - Documented sepsis from other pathogens other than SARS-CoV-2. - Presence of co-morbidities associated, in clinical judgment, with an unfavourable outcome. - Complicated diverticulitis and / or intestinal perforation. - Skin infection in progress (e.g. dermohypodermitis not controlled by antibiotic therapy). - Immuno-suppressive anti-rejection therapy. - Pregnancy or woman of childbearing age who does not use contraceptive and/or breastfeeding measures. - Previous ischemic attack or myocardial infarction. - NYHA class III or IV heart failure. - Severe depressive syndrome or other psychiatric disease which, in the opinion of the doctor, can preclude patient participation in the study. - Presence of known malignant neoplasms. - Clinically significant history of alcohol abuse or drug addiction which, in the opinion of the doctor, may preclude the subject's participation in the study. - Any condition which, in the opinion of the doctor, precludes the possibility of using the study drug provided for in the RCP. - Any other laboratory condition or parameter that, in the doctor's judgment, precludes the subject's participation in the study.
Trial Details
Identifiers
| Identifier | Owner |
|---|---|
| NCT04332913 | ClinicalTrials.gov: US National Institutes of Health |
| 0064468-20 | - |
Trial Dates
-
Initiation Dates
Planned : 01 Apr 2020
Actual : 01 Apr 2020
-
Primary Completion Dates
Planned : 31 Dec 2020
-
End Dates
Planned : 31 Mar 2021
Other Details
- Design cohort; observational; prospective
- Phase of Trial Phase II
- Location Italy
- Focus Proof of concept; Therapeutic Use
Interventions
| Drugs | Route | Formulation |
|---|---|---|
| TocilizumabPrimary Drug |
-
|
-
|
Tocilizumab
Trial Centres
Investigators
| Investigator | Centre Name | Trial Centre Country |
|---|---|---|
|
Roberto Giacomelli, MD
0862434742 roberto.giacomelli@univaq.it
show details
|
Ospedale San Salvatore | Italy |
|
Roberto Giacomelli, MD, PhD
0039 0862 434742 roberto.giacomelli@univaq.it
show details
|
-
|
Centres
| Centre Name | Location | Trial Centre Country |
|---|---|---|
| - |
-
|
-
|
| Ospedale San Salvatore | L'Aquila | Italy |
| University of L'Aquila |
-
|
-
|
Trial History
| Event Date | Event Type | Comment |
|---|---|---|
| 10 Apr 2022 | Other trial event | According to ClinicalTrials.gov, the recruitment status of this study is unknown because the information has not been verified recently (last verified Apr 2020). Updated 10 Apr 2022 |
| 10 Apr 2022 | Other trial event | Last checked against ClinicalTrials.gov record. Updated 10 Apr 2022 |
| 13 Apr 2020 | Biomarker Update | Biomarkers information updated Updated 04 Nov 2021 |
| 09 Apr 2020 | Status change - recruiting | Status changed from not yet recruiting to recruiting. Updated 14 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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