Multicenter Study on the Efficacy and Tolerability of Tocilizumab in the Treatment of Patients With COVID-19 Pneumonia
Latest Information Update: 06 Sep 2023
At a glance
- Drugs Tocilizumab (Primary)
- Indications COVID-19 pneumonia
- Focus Therapeutic Use
- Acronyms TOCIVID-19
- 06 Sep 2023 Status changed from active, no longer recruiting to completed.
- 23 Mar 2023 Planned End Date changed from 19 Dec 2022 to 19 Dec 2023.
- 23 Mar 2023 Planned primary completion date changed from 19 Dec 2021 to 19 Dec 2023.
Most Recent Events
Trial Overview
Purpose
This study project includes a single-arm phase 2 study and a parallel observational cohort study, enrolling patients with COVID-19 pneumonia.
Patients with criteria #4 and #5 who have been already treated with tocilizumab before registration are eligible for the observational retrospective cohort
Primary Endpoints
Lethality rate two weeks after registration
description: 2-week lethality is defined as the ratio of the number of subjects dead within 14 days from study start out of phase 2 patients with baseline information.
time_frame: up to 15 days
Lethality rate one month after registration
description: 1-month lethality is defined as the ratio of the number of subjects dead within 30 days from study start out of phase 2 patients with baseline information.
time_frame: up to 1 month
Other Endpoints
Interleukin-6 level
description: IL-6 levels will be assessed using commercial ELISA method.
time_frame: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month
Lymphocyte count
description: Lymphocyte count assessed by routinely used determination of blood count
time_frame: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month
CRP (C-reactive protein) level
description: CRP is assessed by routinely used determination of CRP
time_frame: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month
PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio)
description: calculated from arterial blood gas analyses (values from 300 to 100)
time_frame: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month
Change of the SOFA (Sequential Organ Failure Assessment)
description: It evaluates 6 variables, each representing an organ system (one for the respiratory, cardiovascular, hepatic, coagulation, renal and neurological systems), and scored from 0 (normal) to 4 (high degree of dysfunction/failure). Thus, the maximum score may range from 0 to 24.
time_frame: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month
Number of participants with treatment-related side effects as assessed by Common Terminology Criteria for Adverse Event (CTCAE) version 5.0
description: graded according to CTCAE citeria (v5.0)
time_frame: during treatment and up to 30 days after the last treatment dose
Radiological response
description: Thoracic CT scan or Chest XR
time_frame: at baseline (optional), after seven days and if clinically indicated (up to 1 month)
Duration of hospitalization
description: Days of hospitalization
time_frame: from baseline up to patient's discharge (up to 1 month)
Remission of respiratory symptoms
description: time to invasive mechanical ventilation (if not previously initiated) calculated from baseline to intubation
time_frame: up to 1 month
Remission of respiratory symptoms
description: time to definitive extubation calculated from intubation (any time occurred) to extubation in days
time_frame: up to 1 month
Remission of respiratory symptoms
description: time to independence from non-invasive mechanical ventilation calculated in days
time_frame: up to 1 month
Remission of respiratory symptoms
description: time to independence from oxygen therapy in days
time_frame: up to 1 month [1]
Diseases Treated
| Indication | Qualifiers | Patient Segments |
|---|---|---|
| COVID-19 pneumonia | treatment | - |
Biomarker
| NCT Number | Biomarker Name | Biomarker Function |
|---|---|---|
| NCT04317092 | C-reactive protein (CRP) | Outcome Measure |
| Interleukin-6 (IL-6) | Outcome Measure |
Subjects
- Subject Type patients
-
Number
Planned: 440
Actual: 402
- Sex male & female
- Age Group ≥ 18 years; adult; elderly
Patient Inclusion Criteria
1. Any gender 2. No age limit 3. Informed consent for participation in the study (consent can be oral if a written consent cannot be expressed. If the subject is incapable of giving an informed consent and an authorized representative is not available without a delay that would, in the opinion of the Investigator, compromise the potential life-saving effect of the treatment this can be administered without consent. Consent to remain in the research should be sought as soon the conditions of the patient will allow it) 4. Virological diagnosis of SARS-CoV-2 infection (real-time PCR) 5. Hospitalized due to clinical/instrumental diagnosis of pneumonia 6. Oxygen saturation at rest in ambient air ≤93% or requiring oxygen therapy or mechanical ventilation either non invasive or invasive (intubated) 7. Patients with criteria #4 and #5 who have been already treated with tocilizumab before registration are eligible for the observational retrospective cohort
Patient Exclusion Criteria
1. Known hypersensitivity to tocilizumab or its excipients 2. Known active infections or other clinical condition that contraindicate tocilizumab and cannot be treated or solved according to the judgement of the clinician 3. ALT / AST> 5 times the upper limit of the normality 4. Neutrophils <500 / mmc 5. Platelets <50.000 / mmc 6. Bowel diverticulitis or perforation
Trial Details
Identifiers
| Identifier | Owner |
|---|---|
| NCT04317092 | ClinicalTrials.gov: US National Institutes of Health |
| EudraCT2020-001110-38 | European Clinical Trials Database |
| TOCIVID19 | - |
Trial Dates
-
Initiation Dates
Actual : 19 Mar 2020
-
Primary Completion Dates
Planned : 19 Dec 2023
-
End Dates
Planned : 19 Dec 2023
Actual : 29 Oct 2020
Other Details
- Design multicentre; observational; open; parallel; prospective; retrospective
- Phase of Trial Phase II
- Location Italy
- Focus Therapeutic Use
Interventions
| Drugs | Route | Formulation |
|---|---|---|
| TocilizumabPrimary Drug | Intravenous | Infusion, Injection |
tocilizumab treatment
All the patients enrolled are treated with tocilizumab. Drug: Tocilizumab Injection (Tocilizumab 8 mg/kg (up to a maximum of 800mg per dose). A second administration (same dose) can be given after 12 hours if respiratory function has not recovered, at discretion of the Investigator.)
Trial Centres
Investigators
| Investigator | Centre Name | Trial Centre Country |
|---|---|---|
| Arturo Montineri, MD | A.O.U. Policlinico V. Emanuele (U.O. di Malattie infettive, U.O. di Anestesia e Rianimazione, U.O. di Medicina d'Urgenza) | Italy |
|
Carlo Salvarani, MD
+39 0522 296684 salvarani.carlo@ausl.re.it
show details
|
Azienda Ospedaliero-Universitaria di Modena | Italy |
| Carmelo Iacobello, MD | AOE Cannizzaro di Catania (U.O. di Malattie Infettive, U.O. di Anestesia e Rianimazione, U.O. | Italy |
|
Cristina Mussini, MD
0594223673 nb.protocolli@unimore.it
show details
|
A.O.U. di Modena (Dipartimento Medicine Specialistiche - Struttura Complessa Malattie Infettive) | Italy |
| Demetrio Labate | Grande Ospedale Metropolitano, Reggio Calabria | Italy |
|
Elisabetta Bertelli, MD
0594225868 ricercainnovazione@aou.mo.it
show details
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A.O.U. di Modena (Dipartimento Chirurgie Generali e Specialità Chirurgiche - Struttura Complessa di Anestesia e Rianimazione II) | Italy |
|
Enrico Clini, MD
0594225868 ricercainnovazione@aou.mo.it
show details
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Dipartimento Medicine Specialistiche - Struttura Complessa Malattie dell'Apparato Respiratorio | Italy |
|
Evelina Tacconelli, MD
045 8128243 - 8128244 evelina.tacconelli@univr.it
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A.O.U. Integrata di Verona (Dip. Malattie Infettive) | Italy |
|
Fabio Franzetti, MD
0331/699270 fabio.franzetti@asst-valleolona.it
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Ospedale di Busto Arsizio ASST Valle Olona (U.O.C. Malattie Infettive) | Italy |
|
Fabio Giuliano Numis, MD
fabiogiuliano.numis@aslnapoli2nord.it
show details
|
Denominazione: UOC di Medicina e Chirurgia d'Accettazione e d'Urgenza dell'Ospedale Santa Maria delle Grazie di Pozzuoli | Italy |
|
Fiorentino Fragranza, MD
+39 08170672571 fiorentino.fragranza@ospedaledeicolli.it
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A.O.R.N. Ospedale dei Colli Monaldi-Cotugno-CTO (U.O.C. Anestesia Rianimazione e terapia intensiva) | Italy |
|
Francesco Cristini, MD
0541705506 - 0541705315 francesco.cristini@auslromagna.it
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Ospedale Infermi, AUSL della Romagna (U.O. Malattie Infettive) | Italy |
|
Francesco Dentali, MD
0332/393056 francesco.dentali@asst-settelaghi.it
show details
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ASST Sette Laghi (Dipartimento di Medicina Interna) | Italy |
|
Francesco Perrone, MD, PhD
+390815903571 f.perrone@istitutotumori.na.it
show details
|
Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale |
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|
Giancarlo Titolo, MD
328 4157022 giancarlo.titolo@ospedalimarchenord.it
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A.O. Ospedali Riuniti Marche Nord - Presidio Ospedaliero San Salvatore di Pesaro (UOC Pronto Soccorso e Medicina d'Urgenza) | Italy |
| Giuseppe Carpinteri, MD | A.O.U. Policlinico V. Emanuele (U.O. di Malattie infettive, U.O. di Anestesia e Rianimazione, U.O. di Medicina d'Urgenza) | Italy |
|
Maria Carmela Piccirillo, MD
+390815903615 m.piccirillo@istitutotumori.na.it
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|
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| Maria Concetta Monea, MD | AOE Cannizzaro di Catania (U.O. di Malattie Infettive, U.O. di Anestesia e Rianimazione, U.O. | Italy |
|
Maria Danzi, MD
331/6237628 maria.danzi@aulss9.veneto.it
show details
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Ospedale Magalini (U.O. Malattie Infettive) | Italy |
|
Massimo Girardis, MD
0594225868 ricercainnovazione@aou.mo.it
show details
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A.O.U. di Modena (Dipartimento Chirurgie Generali e Specialità Chirurgiche - Struttura Complessa di Anestesia e Rianimazione I) | Italy |
|
Maurizio Fusari, MD
0544285918 maurizio.fusari@auslromagna.it
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Ospedale Santa Maria delle Croci, AUSL della Romagna (U.O. Anestesia e Rianimazione) | Italy |
|
Paola Faggioli, MD
0331449175-919 paola.faggioli@sst-ovestmi.it
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ASST OVEST MILANESE presidi Legnano - Magenta | Italy |
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Paolo Grossi, MD
0332/393056 paolo.grossi@asst-settelaghi.it
show details
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ASST Sette Laghi (U.O.C. Malattie Infettive e Tropicali) | Italy |
|
Roberto Cauda, MD
06 3015 4945 roberto.cauda@policlinicogemelli.it
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Policlinico Gemelli (U.O.C. Dipartimento Scienze di Laboratorio e Infettivologiche) | Italy |
|
Roberto Parrella, MD
+39 0817067584 roberto.parrella@ospedaledeicolli.it
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A.O.R.N. Ospedale dei Colli Monaldi-Cotugno-CTO (U.O.C. Malattie Infettive ad indirizzo respiratorio) | Italy |
| Salvo Nicosia, MD | A.O.U. Policlinico V. Emanuele (U.O. di Malattie infettive, U.O. di Anestesia e Rianimazione, U.O. di Medicina d'Urgenza) | Italy |
|
Stobbione Paolo, MD
0131/206860 pstobbione@ospedale.al.it
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Azienda Ospedaliera "SS. Antonio e Biagio e C. Arrigo" (Dipartimento Internistico SSD Reumatologia) | Italy |
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Vincenzo Montesarchio, MD
+39 0817065268 vincenzo.montesarchio@ospedaledeicolli.it
show details
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A.O.R.N. Ospedale dei Colli Monaldi-Cotugno-CTO (U.O.C. Oncologia) | Italy |
|
Walter Ageno, MD
0332/393056 walter.ageno@asst-settelaghi.it
show details
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ASST Sette Laghi (Dipartimento Emergenze ed Urgenze) | Italy |
Centres
| Centre Name | Location | Trial Centre Country |
|---|---|---|
| - |
-
|
-
|
| A.O. Ospedali Riuniti Marche Nord - Presidio Ospedaliero San Salvatore di Pesaro (UOC Pronto Soccorso e Medicina d'Urgenza) | Pesaro | Italy |
| A.O.R.N. Ospedale dei Colli Monaldi-Cotugno-CTO (U.O.C. Anestesia Rianimazione e terapia intensiva) | Naples | Italy |
| A.O.R.N. Ospedale dei Colli Monaldi-Cotugno-CTO (U.O.C. Malattie Infettive ad indirizzo respiratorio) | Naples | Italy |
| A.O.R.N. Ospedale dei Colli Monaldi-Cotugno-CTO (U.O.C. Oncologia) | Naples | Italy |
| A.O.U. di Modena (Dipartimento Chirurgie Generali e Specialità Chirurgiche - Struttura Complessa di Anestesia e Rianimazione I) | Modena | Italy |
| A.O.U. di Modena (Dipartimento Chirurgie Generali e Specialità Chirurgiche - Struttura Complessa di Anestesia e Rianimazione II) | Modena | Italy |
| A.O.U. di Modena (Dipartimento Medicine Specialistiche - Struttura Complessa Malattie Infettive) | Modena | Italy |
| A.O.U. Integrata di Verona (Dip. Malattie Infettive) | Verona | Italy |
| A.O.U. Policlinico V. Emanuele (U.O. di Malattie infettive, U.O. di Anestesia e Rianimazione, U.O. di Medicina d'Urgenza) | Catania | Italy |
| AOE Cannizzaro di Catania (U.O. di Malattie Infettive, U.O. di Anestesia e Rianimazione, U.O. | Catania | Italy |
| ASST OVEST MILANESE presidi Legnano - Magenta | Magenta | Italy |
| ASST Sette Laghi (Dipartimento di Medicina Interna) | Varese | Italy |
| ASST Sette Laghi (Dipartimento Emergenze ed Urgenze) | Varese | Italy |
| ASST Sette Laghi (U.O.C. Anestesia e Rianimazione Neurochirurgica e Generale) | Varese | Italy |
| ASST Sette Laghi (U.O.C. Malattie Infettive e Tropicali) | Varese | Italy |
| Azienda Ospedaliera "SS. Antonio e Biagio e C. Arrigo" (Dipartimento Internistico SSD Reumatologia) | Alessandria | Italy |
| Azienda Ospedaliero-Universitaria di Modena | Modena | Italy |
| Denominazione: UOC di Medicina e Chirurgia d'Accettazione e d'Urgenza dell'Ospedale Santa Maria delle Grazie di Pozzuoli | Pozzuoli | Italy |
| Dipartimento Medicine Specialistiche - Struttura Complessa Malattie dell'Apparato Respiratorio | Modena | Italy |
| Grande Ospedale Metropolitano, Reggio Calabria | Reggio Calabria | Italy |
| ISTITUTO NAZIONALE PER LO STUDIO E LA CURA DEI TUMORI - FONDAZIONE "G. PASCALE" |
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|
Italy |
| Istituto Nazionale Tumori, IRCCS, Fondazione G. Pascale |
-
|
-
|
| Ospedale Annunziata Azienda Ospedaliera di Cosenza (U.O.C. Malattie Infettive) | Cosenza | Italy |
| Ospedale di Busto Arsizio ASST Valle Olona (U.O.C. Malattie Infettive) | Busto Arsizio | Italy |
| Ospedale Infermi, AUSL della Romagna (U.O. Malattie Infettive) | Rimini | Italy |
| Ospedale Magalini (U.O. Malattie Infettive) | Villafranca Di Verona | Italy |
| Ospedale Santa Maria delle Croci, AUSL della Romagna (U.O. Anestesia e Rianimazione) | Ravenna | Italy |
| Policlinico Gemelli (U.O.C. Dipartimento Scienze di Laboratorio e Infettivologiche) | Rome | Italy |
Trial History
| Event Date | Event Type | Comment |
|---|---|---|
| 06 Sep 2023 | Other trial event | Last checked against European Clinical Trials Database record. Updated 06 Sep 2023 |
| 06 Sep 2023 | Status change - completed | Status changed from active, no longer recruiting to completed. Updated 06 Sep 2023 |
| 27 Mar 2023 | Other trial event | Last checked against ClinicalTrials.gov record. Updated 27 Mar 2023 |
| 23 Mar 2023 | Completion date | Planned End Date changed from 19 Dec 2022 to 19 Dec 2023. Updated 27 Mar 2023 |
| 23 Mar 2023 | Other trial event | Planned primary completion date changed from 19 Dec 2021 to 19 Dec 2023. Updated 27 Mar 2023 |
| 22 Dec 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 October 2020). Updated 22 Dec 2022 |
| 03 Mar 2021 | Biomarker Update | Biomarkers information updated Updated 04 Nov 2021 |
| 02 Mar 2021 | Other trial event | Planned primary completion date changed from 19 Dec 2020 to 19 Dec 2021. Updated 04 Mar 2021 |
| 01 Nov 2020 | Other trial event | Primary analysis will include patients enrolled in the phase 2 study. Results of the primary analysis will be validated in the prospective cohort of patients consecutively registered after phase 2 closure from March 20 to March 24, who were potentially eligible for the phase 2 study as per trial design published in the Contemporary Clinical Trials Updated 30 Dec 2020 |
| 01 Nov 2020 | Other trial event | Trial design published in the Contemporary Clinical Trials Updated 30 Dec 2020 |
| 19 Oct 2020 | Status change - active, no longer recruiting | Status changed from recruiting to active, no longer recruiting. Updated 26 Oct 2020 |
| 08 Apr 2020 | Other trial event | New source identified and integrated (ClinicalTrials.gov: NCT04317092). Updated 08 Apr 2020 |
| 03 Apr 2020 | Other trial event | Planned number of patients changed from 330 to 440. Updated 08 Apr 2020 |
| 30 Mar 2020 | New trial record | New trial record Updated 30 Mar 2020 |
References
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ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2023;.
Available from: URL: http://clinicaltrials.gov -
European Clinical Trials Database. Trial-Reg 2023;.
Available from: URL: https://www.clinicaltrialsregister.eu -
Piccirillo MC, Ascierto P, Atripaldi L, Cascella M, Costantini M, Dolci G, et al. TOCIVID-19 - A multicenter study on the efficacy and tolerability of tocilizumab in the treatment of patients with COVID-19 pneumonia. Study protocol. Contemp-Clin-Trials 2020;98106165.
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