Efficacy of Early Administration of Tocilizumab in COVID-19 Patients

COVID-19 Pneumonia Clinical Trial

Official title:

An Open-label Randomized Multicenter Study to Evaluate the Efficacy of Early Administration of Tocilizumab (TCZ) in Patients With COVID-19 Pneumonia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04346355
• Other study ID #: RCT-TCZ-COVID-19
• Secondary ID: 2020-001386-37
• Status: Terminated
• Phase: Phase 2
• Start date: March 31, 2020
• Est. completion date: June 6, 2020

Study information

• Verified date: June 2020
• Source: Azienda Unità Sanitaria Locale Reggio Emilia
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 126
• Est. completion date: June 6, 2020
• Est. primary completion date: June 6, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• COVID-19 Pneumonia
• Pneumonia

Intervention

Drug:
• Tocilizumab
In case of aggravation of COVID-19 pneumonia, according to protocol criteria, participants will receive 8 mg/kg IV up to a maximum of 800 mg with repetition of the same dosage after 12 hours

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo	Alessandria
Italy	Policlinico Sant'Orsola Malpighi	Bologna
Italy	ASST Cremona	Cremona
Italy	Azienda Ospedaliera S. Croce e Carle	Cuneo
Italy	Azienda Ospedaliero Universitaria Ferrara	Ferrara
Italy	Azienda Ospedaliero Universitaria Careggi	Firenze
Italy	Ospedale Evangelico Internazionale di Genova	Genova
Italy	Ospedale di Guastalla	Guastalla	RE
Italy	Azienda Sociosanitaria ASL 1 ,Imperia	Imperia
Italy	Azienda Sociosanitaria ASL 5 La Spezia	La Spezia
Italy	ASST Mantova - Ospedale Carlo Poma	Mantova
Italy	IRCCS Istituto Auxologico Italiano Milano	Milano
Italy	Azienda Ospedaliero-Universitaria "Maggiore della Carità" di Novara	Novara
Italy	Ospedali Riuniti Padova Sud - ULSS 6 Euganea	Padova
Italy	Azienda Ospedaliero-Universitaria Parma	Parma
Italy	Azienda Unità Sanitaria Locale di Piacenza	Piacenza
Italy	Azienda Ospedaliera Universitaria Pisana	Pisa
Italy	Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia	Reggio Emilia	RE
Italy	AO Ordine Mauriziano di Torino	Torino
Italy	ASST Bergamo Ovest -Treviglio	Treviglio
Italy	AULSS 2 Marca Trevigiana	Treviso
Italy	AULSS2 Marca Trevigiana - Ospedale Vittorio Veneto	Treviso
Italy	AULSS 3 Serenissima Ospedale "Dell'Angelo"	Venezia
Italy	Azienda Ospedaliera Universitaria Integrata di Verona	Verona
Italy	IRCCS Sacro Cuore Don Calabria	Verona

Sponsors (1)

Lead Sponsor	Collaborator
Azienda Unità Sanitaria Locale Reggio Emilia

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Entry into Intensive Care with invasive mechanical ventilation or death from any cause or clinical aggravation	Entry into Intensive Care with invasive mechanical ventilation or death from any cause or clinical aggravation documented by the finding of a PaO2 / FiO2 ratio <150mm / Hg confirmed by a second arterial blood gas (ABG) measurement within four hours	two weeks from participants' allocation to study arm
Secondary	Death from any cause	Death	Two weeks from participants' allocation to study arm
Secondary	Tocilizumab toxicity	Adverse events (AE) classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale	Two weeks from participants' allocation to study arm
Secondary	Levels of interleukin-6 and C-reactive protein (CRP) and their correlation with the effectiveness of the treatment	Levels of ferritin, lactate dehydrogenase and D-dimer and their correlation with the effectiveness of the treatment	Two weeks from participants' allocation to study arm
Secondary	Evaluate the progress of the PaO2 / FiO2 ratio	Changes from baseline of the PaO2 / FiO2 ratio	Two weeks from participants' allocation to study arm
Secondary	Evaluate the trend over time of the lymphocyte count	Changes from baseline of the lymphocyte count	Two weeks from participants' allocation to study arm