Clinical trial NCT04346355: Efficacy of Early Administration of Tocilizumab in COVID-19 Patients
Official title: An Open-label Randomized Multicenter Study to Evaluate the Efficacy of Early Administration of Tocilizumab (TCZ) in Patients With COVID-19 Pneumonia
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID-19 Pneumonia
Lead sponsor: Azienda USL Reggio Emilia - IRCCS
Sponsor class: OTHER_GOV
First posted: 2020-04-15
Enrollment: 126
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The clinical study aims at assessing whether early administration of Tocilizumab compared to late administration of Tocilizumab can reduce the number of patients with COVID-19 pneumonia who require mechanical ventilation. The clinical study includes patients with recent-onset COVID-19 pneumonia who require hospital care, but not invasive or semi-invasive mechanical ventilation procedures.


Eligibility criteria: Inclusion Criteria:

* age \> 18 years
* Informed consent for participation in the study
* Real time polymerase chain reaction (PCR) diagnosis of Sars-CoV2 infection
* Hospitalization due to clinical / instrumental diagnosis (high resolution chest CT scan or chest x-ray or pulmonary ultrasound)
* Presence of acute respiratory distress syndrome with arterial partial pressure of oxygen / fraction of inspired oxygen (PaO2 / FiO2) between 200 and 300 mm/Hg
* Presence of exaggerated inflammatory response defined by the presence of at least 1 of the following criteria:
* At least one body temperature measurement \>38° C in the past two days;
* Serum CRP greater than or equal to 10 mg/dl;
* CRP increase of at least twice the basal value

Exclusion Criteria:

* Patients with respiratory distress syndrome with arterial partial pressure of oxygen / fraction of inspired oxygen (PaO2 / FiO2) \<200 mm/Hg or
* Patients in non-invasive ventilation or
* Patients in invasive ventilation or presence of shock or presence of concomitant organ failure that requires admission to the Intensive Care Unit
* Severe heart and kidney failure
* Pregnant or breastfeeding patient
* Patient who, in the opinion of the clinician or by the patient's express will, will not go to intensive care regardless of the evolution of the lung picture.
* Known hypersensitivity to TCZ or its excipients
* Patient being treated with immuno-depressors or anti-rejection drugs
* Known active infections or other clinical conditions that contraindicate TCZ and cannot be treated or resolved according to the physician's judgment
* glutamate-pyruvate transaminase (GPT) or glutamine oxaloacetic transaminase (GOT) \> 5 times the upper limit of the norm
* Neutrophils \<500 /mmc
* Platelets \<50.000 /mmc
* Diverticulitis or intestinal perforation
* Suspicion of latent tuberculosis

Primary outcomes:
measure: Entry into Intensive Care with invasive mechanical ventilation or death from any cause or clinical aggravation
timeFrame: two weeks from participants' allocation to study arm
Secondary outcomes:
measure: Death from any cause
timeFrame: Two weeks from participants' allocation to study arm
measure: Tocilizumab toxicity
timeFrame: Two weeks from participants' allocation to study arm
measure: Levels of interleukin-6 and C-reactive protein (CRP) and their correlation with the effectiveness of the treatment
timeFrame: Two weeks from participants' allocation to study arm
measure: Evaluate the progress of the PaO2 / FiO2 ratio
timeFrame: Two weeks from participants' allocation to study arm
measure: Evaluate the trend over time of the lymphocyte count
timeFrame: Two weeks from participants' allocation to study arm
Other outcomes:
Locations:
city: Guastalla
country: Italy
facility: Ospedale di Guastalla
state: RE
city: Reggio Emilia
country: Italy
facility: Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia
state: RE
city: Alessandria
country: Italy
facility: Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola Malpighi
city: Cremona
country: Italy
facility: ASST Cremona
city: Cuneo
country: Italy
facility: Azienda Ospedaliera S. Croce e Carle
city: Ferrara
country: Italy
facility: Azienda Ospedaliero Universitaria Ferrara
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
city: Genova
country: Italy
facility: Ospedale Evangelico Internazionale di Genova
city: Imperia
country: Italy
facility: Azienda Sociosanitaria ASL 1 ,Imperia
city: La Spezia
country: Italy
facility: Azienda Sociosanitaria ASL 5 La Spezia
city: Mantova
country: Italy
facility: ASST Mantova - Ospedale Carlo Poma
city: Milano
country: Italy
facility: IRCCS Istituto Auxologico Italiano Milano
city: Novara
country: Italy
facility: Azienda Ospedaliero-Universitaria "Maggiore della Carità" di Novara
city: Padova
country: Italy
facility: Ospedali Riuniti Padova Sud - ULSS 6 Euganea
city: Parma
country: Italy
facility: Azienda Ospedaliero-Universitaria Parma
city: Piacenza
country: Italy
facility: Azienda Unità Sanitaria Locale di Piacenza
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana
city: Torino
country: Italy
facility: AO Ordine Mauriziano di Torino
city: Treviglio
country: Italy
facility: ASST Bergamo Ovest -Treviglio
city: Treviso
country: Italy
facility: AULSS 2 Marca Trevigiana
city: Treviso
country: Italy
facility: AULSS2 Marca Trevigiana - Ospedale Vittorio Veneto
city: Venezia
country: Italy
facility: AULSS 3 Serenissima Ospedale "Dell'Angelo"
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata di Verona
city: Verona
country: Italy
facility: IRCCS Sacro Cuore Don Calabria
Study officials:
affiliation: Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia
name: Carlo Salvarani, M.D.
role: STUDY_DIRECTOR
affiliation: Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia
name: Massimo Costantini, Ph.D.
role: STUDY_DIRECTOR
References:
citation: Salvarani C, Dolci G, Massari M, Merlo DF, Cavuto S, Savoldi L, Bruzzi P, Boni F, Braglia L, Turra C, Ballerini PF, Sciascia R, Zammarchi L, Para O, Scotton PG, Inojosa WO, Ravagnani V, Salerno ND, Sainaghi PP, Brignone A, Codeluppi M, Teopompi E, Milesi M, Bertomoro P, Claudio N, Salio M, Falcone M, Cenderello G, Donghi L, Del Bono V, Colombelli PL, Angheben A, Passaro A, Secondo G, Pascale R, Piazza I, Facciolongo N, Costantini M; RCT-TCZ-COVID-19 Study Group. Effect of Tocilizumab vs Standard Care on Clinical Worsening in Patients Hospitalized With COVID-19 Pneumonia: A Randomized Clinical Trial. JAMA Intern Med. 2021 Jan 1;181(1):24-31. doi: 10.1001/jamainternmed.2020.6615.