Clinical trial NCT04317092: Tocilizumab in COVID-19 Pneumonia (TOCIVID-19)
Official title: Multicenter Study on the Efficacy and Tolerability of Tocilizumab in the Treatment of Patients With COVID-19 Pneumonia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: COVID-19 Pneumonia
Keywords: COVID-19
pneumonia
tocilizumab
Interleukin-6
Lead sponsor: National Cancer Institute, Naples
Sponsor class: OTHER
First posted: 2020-03-20
Enrollment: 402
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a multicenter, single-arm, open-label, phase 2 study. All the patients enrolled are treated with tocilizumab
Primary purpose: TREATMENT

Brief summary: This study project includes a single-arm phase 2 study and a parallel cohort study, enrolling patients with COVID-19 pneumonia.

Detailed description: Phase 2 study: this is a multicenter, single-arm, open-label, phase 2 study. All the patients enrolled are treated with tocilizumab. Two-week (14 days) and one-month (30 days) lethality rates are the co-primary endpoints.

The parallel cohort includes patients who are treated with tocilizumab and cannot enter the phase 2 study because:

1. emergency conditions or infrastructural or operational limits prevented registration before the administration of the experimental drug or
2. they had been intubated more than 24 hours before registration or
3. the phase 2 study has been closed due to reached sample size.

This means that, after closure of the phase 2 enrolment, patients who might be eligible for the phase 2 study will be included in the observational cohort study.

The same information planned for the phase 2 cohort is required also for the parallel cohort study whose sample size is not defined a priori, and that will close at the end of the overall project. All the patients enrolled are treated with tocilizumab.

In both study groups (phase 2 and parallel cohort), participants receive one dose of 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.

Eligibility criteria: 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

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

Primary outcomes:
measure: Lethality rate two weeks after registration
timeFrame: up to 15 days
measure: Lethality rate one month after registration
timeFrame: up to 1 month
Secondary outcomes:
measure: Interleukin-6 level
timeFrame: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month
measure: Lymphocyte count
timeFrame: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month
measure: CRP (C-reactive protein) level
timeFrame: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month
measure: PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio)
timeFrame: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month
measure: Change of the SOFA (Sequential Organ Failure Assessment)
timeFrame: baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month
measure: Number of participants with treatment-related side effects as assessed by Common Terminology Criteria for Adverse Event (CTCAE) version 5.0
timeFrame: during treatment and up to 30 days after the last treatment dose
measure: Radiological response
timeFrame: at baseline (optional), after seven days and if clinically indicated (up to 1 month)
measure: Duration of hospitalization
timeFrame: from baseline up to patient's discharge (up to 1 month)
measure: Remission of respiratory symptoms
timeFrame: up to 1 month
measure: Remission of respiratory symptoms
timeFrame: up to 1 month
measure: Remission of respiratory symptoms
timeFrame: up to 1 month
measure: Remission of respiratory symptoms
timeFrame: up to 1 month
Other outcomes:
Locations:
city: Alessandria
country: Italy
facility: Azienda Ospedaliera "SS. Antonio e Biagio e C. Arrigo" (Dipartimento Internistico SSD Reumatologia)
city: Busto Arsizio
country: Italy
facility: Ospedale di Busto Arsizio ASST Valle Olona (U.O.C. Malattie Infettive)
city: Catania
country: Italy
facility: A.O.U. Policlinico V. Emanuele (U.O. di Malattie infettive, U.O. di Anestesia e Rianimazione, U.O. di Medicina d'Urgenza)
city: Catania
country: Italy
facility: AOE Cannizzaro di Catania (U.O. di Malattie Infettive, U.O. di Anestesia e Rianimazione, U.O.
city: Cosenza
country: Italy
facility: Ospedale Annunziata Azienda Ospedaliera di Cosenza (U.O.C. Malattie Infettive)
city: Magenta
country: Italy
facility: ASST OVEST MILANESE presidi Legnano - Magenta
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena
city: Modena
country: Italy
facility: A.O.U. di Modena (Dipartimento Chirurgie Generali e Specialità Chirurgiche - Struttura Complessa di Anestesia e Rianimazione I)
city: Modena
country: Italy
facility: A.O.U. di Modena (Dipartimento Chirurgie Generali e Specialità Chirurgiche - Struttura Complessa di Anestesia e Rianimazione II)
city: Modena
country: Italy
facility: A.O.U. di Modena (Dipartimento Medicine Specialistiche - Struttura Complessa Malattie Infettive)
city: Modena
country: Italy
facility: Dipartimento Medicine Specialistiche - Struttura Complessa Malattie dell'Apparato Respiratorio
city: Naples
country: Italy
facility: A.O.R.N. Ospedale dei Colli Monaldi-Cotugno-CTO (U.O.C. Oncologia)
city: Naples
country: Italy
facility: National Cancer Institute
city: Naples
country: Italy
facility: A.O.R.N. Ospedale dei Colli Monaldi-Cotugno-CTO (U.O.C. Anestesia Rianimazione e terapia intensiva)
city: Naples
country: Italy
facility: A.O.R.N. Ospedale dei Colli Monaldi-Cotugno-CTO (U.O.C. Malattie Infettive ad indirizzo respiratorio)
city: Pesaro
country: Italy
facility: A.O. Ospedali Riuniti Marche Nord - Presidio Ospedaliero San Salvatore di Pesaro (UOC Pronto Soccorso e Medicina d'Urgenza)
city: Pozzuoli
country: Italy
facility: Denominazione: UOC di Medicina e Chirurgia d'Accettazione e d'Urgenza dell'Ospedale Santa Maria delle Grazie di Pozzuoli
city: Ravenna
country: Italy
facility: Ospedale Santa Maria delle Croci, AUSL della Romagna (U.O. Anestesia e Rianimazione)
city: Reggio Calabria
country: Italy
facility: Grande Ospedale Metropolitano, Reggio Calabria
city: Rimini
country: Italy
facility: Ospedale Infermi, AUSL della Romagna (U.O. Malattie Infettive)
city: Rome
country: Italy
facility: Policlinico Gemelli (U.O.C. Dipartimento Scienze di Laboratorio e Infettivologiche)
city: Varese
country: Italy
facility: ASST Sette Laghi (Dipartimento di Medicina Interna)
city: Varese
country: Italy
facility: ASST Sette Laghi (Dipartimento Emergenze ed Urgenze)
city: Varese
country: Italy
facility: ASST Sette Laghi (U.O.C. Anestesia e Rianimazione Neurochirurgica e Generale)
city: Varese
country: Italy
facility: ASST Sette Laghi (U.O.C. Malattie Infettive e Tropicali)
city: Verona
country: Italy
facility: A.O.U. Integrata di Verona (Dip. Malattie Infettive)
city: Villafranca Di Verona
country: Italy
facility: Ospedale Magalini (U.O. Malattie Infettive)
Study officials:
affiliation: Istituto Nazionale Tumori IRCCS - Fondazione G. Pascale
name: Francesco Perrone, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Perrone F, Piccirillo MC, Ascierto PA, Salvarani C, Parrella R, Marata AM, Popoli P, Ferraris L, Marrocco-Trischitta MM, Ripamonti D, Binda F, Bonfanti P, Squillace N, Castelli F, Muiesan ML, Lichtner M, Calzetti C, Salerno ND, Atripaldi L, Cascella M, Costantini M, Dolci G, Facciolongo NC, Fraganza F, Massari M, Montesarchio V, Mussini C, Negri EA, Botti G, Cardone C, Gargiulo P, Gravina A, Schettino C, Arenare L, Chiodini P, Gallo C; TOCIVID-19 investigators, Italy. Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial. J Transl Med. 2020 Oct 21;18(1):405. doi: 10.1186/s12967-020-02573-9.
citation: Chiodini P, Arenare L, Piccirillo MC, Perrone F, Gallo C. A phase 2, open label, multicenter, single arm study of tocilizumab on the efficacy and tolerability of tocilizumab in the treatment of patients with COVID-19 pneumonia (TOCIVID-19 trial): Statistical analysis plan. Contemp Clin Trials Commun. 2020 Dec;20:100665. doi: 10.1016/j.conctc.2020.100665. Epub 2020 Oct 7.
citation: Piccirillo MC, Ascierto P, Atripaldi L, Cascella M, Costantini M, Dolci G, Facciolongo N, Fraganza F, Marata A, Massari M, Montesarchio V, Mussini C, Negri EA, Parrella R, Popoli P, Botti G, Arenare L, Chiodini P, Gallo C, Salvarani C, Perrone F. 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 Nov;98:106165. doi: 10.1016/j.cct.2020.106165. Epub 2020 Oct 6.