Tocilizumab in COVID-19 Pneumonia (TOCIVID-19)
- Registration Number
- NCT04317092
- Lead Sponsor
- National Cancer Institute, Naples
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 402
- Any gender
- No age limit
- 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)
- Virological diagnosis of SARS-CoV-2 infection (real-time PCR)
- Hospitalized due to clinical/instrumental diagnosis of pneumonia
- Oxygen saturation at rest in ambient air ≤93% or requiring oxygen therapy or mechanical ventilation either non invasive or invasive (intubated)
- Patients with criteria #4 and #5 who have been already treated with tocilizumab before registration are eligible for the observational retrospective cohort
- Known hypersensitivity to tocilizumab or its excipients
- Known active infections or other clinical condition that contraindicate tocilizumab and cannot be treated or solved according to the judgement of the clinician
- ALT / AST> 5 times the upper limit of the normality
- Neutrophils <500 / mmc
- Platelets <50.000 / mmc
- Bowel diverticulitis or perforation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description tocilizumab treatment Tocilizumab Injection All the patients enrolled are treated with tocilizumab.
- Primary Outcome Measures
Name Time Method Lethality rate two weeks after registration up to 15 days 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.
Lethality rate one month after registration up to 1 month 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.
- Secondary Outcome Measures
Name Time Method Lymphocyte count baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month Lymphocyte count assessed by routinely used determination of blood count
PaO2 (partial pressure of oxygen) / FiO2 (fraction of inspired oxygen, FiO2) ratio (or P/F ratio) baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month calculated from arterial blood gas analyses (values from 300 to 100)
Remission of respiratory symptoms up to 1 month time to independence from oxygen therapy in days
Interleukin-6 level baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month IL-6 levels will be assessed using commercial ELISA method.
CRP (C-reactive protein) level baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month CRP is assessed by routinely used determination of CRP
Change of the SOFA (Sequential Organ Failure Assessment) baseline, during treatment (cycle 1 and 2 every 12 hours) up to 1 month 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.
Number of participants with treatment-related side effects as assessed by Common Terminology Criteria for Adverse Event (CTCAE) version 5.0 during treatment and up to 30 days after the last treatment dose graded according to CTCAE citeria (v5.0)
Radiological response at baseline (optional), after seven days and if clinically indicated (up to 1 month) Thoracic CT scan or Chest XR
Duration of hospitalization from baseline up to patient's discharge (up to 1 month) Days of hospitalization
Trial Locations
- Locations (27)
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
Ospedale Annunziata Azienda Ospedaliera di Cosenza (U.O.C. Malattie Infettive)
🇮🇹Cosenza, 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
Azienda Ospedaliero-Universitaria di Modena
🇮🇹Modena, 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
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
Ospedale Santa Maria delle Croci, AUSL della Romagna (U.O. Anestesia e Rianimazione)
🇮🇹Ravenna, Italy
A.O.R.N. Ospedale dei Colli Monaldi-Cotugno-CTO (U.O.C. Oncologia)
🇮🇹Naples, Italy
National Cancer Institute
🇮🇹Naples, Italy
A.O.R.N. Ospedale dei Colli Monaldi-Cotugno-CTO (U.O.C. Malattie Infettive ad indirizzo respiratorio)
🇮🇹Naples, Italy
Denominazione: UOC di Medicina e Chirurgia d'Accettazione e d'Urgenza dell'Ospedale Santa Maria delle Grazie di Pozzuoli
🇮🇹Pozzuoli, Italy
A.O. Ospedali Riuniti Marche Nord - Presidio Ospedaliero San Salvatore di Pesaro (UOC Pronto Soccorso e Medicina d'Urgenza)
🇮🇹Pesaro, Italy
Grande Ospedale Metropolitano, Reggio Calabria
🇮🇹Reggio Calabria, Italy
Policlinico Gemelli (U.O.C. Dipartimento Scienze di Laboratorio e Infettivologiche)
🇮🇹Rome, Italy
Ospedale Infermi, AUSL della Romagna (U.O. Malattie Infettive)
🇮🇹Rimini, 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. Malattie Infettive e Tropicali)
🇮🇹Varese, Italy
ASST Sette Laghi (U.O.C. Anestesia e Rianimazione Neurochirurgica e Generale)
🇮🇹Varese, Italy
A.O.U. Integrata di Verona (Dip. Malattie Infettive)
🇮🇹Verona, Italy
Ospedale Magalini (U.O. Malattie Infettive)
🇮🇹Villafranca Di Verona, Italy