Tocilizumab in COVID-19 Pneumonia (TOCIVID-19)

COVID-19 Pneumonia Clinical Trial

— TOCIVID-19  

Official title:

Multicenter Study on the Efficacy and Tolerability of Tocilizumab in the Treatment of Patients With COVID-19 Pneumonia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04317092
• Other study ID #: TOCIVID-19
• Secondary ID: 2020-001110-38
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: March 19, 2020
• Est. completion date: December 19, 2023

Study information

• Verified date: March 2023
• Source: National Cancer Institute, Naples
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 402
• Est. completion date: December 19, 2023
• Est. primary completion date: December 19, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19
• COVID-19 Pneumonia
• Pneumonia

Intervention

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.

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera "SS. Antonio e Biagio e C. Arrigo" (Dipartimento Internistico SSD Reumatologia)	Alessandria
Italy	Ospedale di Busto Arsizio ASST Valle Olona (U.O.C. Malattie Infettive)	Busto Arsizio
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	Ospedale Annunziata Azienda Ospedaliera di Cosenza (U.O.C. Malattie Infettive)	Cosenza
Italy	ASST OVEST MILANESE presidi Legnano - Magenta	Magenta
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	Azienda Ospedaliero-Universitaria di Modena	Modena
Italy	Dipartimento Medicine Specialistiche - Struttura Complessa Malattie dell'Apparato Respiratorio	Modena
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	National Cancer Institute	Naples
Italy	A.O. Ospedali Riuniti Marche Nord - Presidio Ospedaliero San Salvatore di Pesaro (UOC Pronto Soccorso e Medicina d'Urgenza)	Pesaro
Italy	Denominazione: UOC di Medicina e Chirurgia d'Accettazione e d'Urgenza dell'Ospedale Santa Maria delle Grazie di Pozzuoli	Pozzuoli
Italy	Ospedale Santa Maria delle Croci, AUSL della Romagna (U.O. Anestesia e Rianimazione)	Ravenna
Italy	Grande Ospedale Metropolitano, Reggio Calabria	Reggio Calabria
Italy	Ospedale Infermi, AUSL della Romagna (U.O. Malattie Infettive)	Rimini
Italy	Policlinico Gemelli (U.O.C. Dipartimento Scienze di Laboratorio e Infettivologiche)	Rome
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	A.O.U. Integrata di Verona (Dip. Malattie Infettive)	Verona
Italy	Ospedale Magalini (U.O. Malattie Infettive)	Villafranca Di Verona

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute, Naples

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lethality rate two weeks after registration	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.	up to 15 days
Primary	Lethality rate one month after registration	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.	up to 1 month
Secondary	Interleukin-6 level	IL-6 levels will be assessed using commercial ELISA method.	baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month
Secondary	Lymphocyte count	Lymphocyte count assessed by routinely used determination of blood count	baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month
Secondary	CRP (C-reactive protein) level	CRP is assessed by routinely used determination of CRP	baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month
Secondary	PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio)	calculated from arterial blood gas analyses (values from 300 to 100)	baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month
Secondary	Change of the SOFA (Sequential Organ Failure Assessment)	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.	baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month
Secondary	Number of participants with treatment-related side effects as assessed by Common Terminology Criteria for Adverse Event (CTCAE) version 5.0	graded according to CTCAE citeria (v5.0)	during treatment and up to 30 days after the last treatment dose
Secondary	Radiological response	Thoracic CT scan or Chest XR	at baseline (optional), after seven days and if clinically indicated (up to 1 month)
Secondary	Duration of hospitalization	Days of hospitalization	from baseline up to patient's discharge (up to 1 month)
Secondary	Remission of respiratory symptoms	time to invasive mechanical ventilation (if not previously initiated) calculated from baseline to intubation	up to 1 month
Secondary	Remission of respiratory symptoms	time to definitive extubation calculated from intubation (any time occurred) to extubation in days	up to 1 month
Secondary	Remission of respiratory symptoms	time to independence from non-invasive mechanical ventilation calculated in days	up to 1 month
Secondary	Remission of respiratory symptoms	time to independence from oxygen therapy in days	up to 1 month