Efficacy of Early Administration of Tocilizumab in COVID-19 Patients

Phase 2

Terminated

• Conditions: COVID-19 Pneumonia
• Interventions: Drug: Tocilizumab

• Registration Number: NCT04346355
• Lead Sponsor: Azienda Unità Sanitaria Locale Reggio Emilia

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-03-31
• Study First Submitted: 2020-04-12
• Study First Submitted QC: 2020-04-14
• Study First Posted: 2020-04-15
• Status Verified: 2020-06
• Primary Completion: 2020-06-06
• Study Completion: 2020-06-06
• Last Update Submitted: 2020-06-18
• Last Update Posted: 2020-06-22

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 126

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental Arm	Tocilizumab	Tocilizumab within 8 hours from entering the study + standard of care; 8 mg/kg IV up to a maximum of 800 mg with repetition of the same dosage after 12 hours
Control Arm	Tocilizumab	Standard of care; In the event 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

Primary Outcome Measures

Name	Time	Method
Entry into Intensive Care with invasive mechanical ventilation or death from any cause or clinical aggravation	two weeks from participants' allocation to study arm	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

Secondary Outcome Measures

Name	Time	Method
Death from any cause	Two weeks from participants' allocation to study arm	Death
Tocilizumab toxicity	Two weeks from participants' allocation to study arm	Adverse events (AE) classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale
Levels of interleukin-6 and C-reactive protein (CRP) and their correlation with the effectiveness of the treatment	Two weeks from participants' allocation to study arm	Levels of ferritin, lactate dehydrogenase and D-dimer and their correlation with the effectiveness of the treatment
Evaluate the progress of the PaO2 / FiO2 ratio	Two weeks from participants' allocation to study arm	Changes from baseline of the PaO2 / FiO2 ratio
Evaluate the trend over time of the lymphocyte count	Two weeks from participants' allocation to study arm	Changes from baseline of the lymphocyte count

Trial Locations

Locations (25)

Ospedale di Guastalla; 🇮🇹 Guastalla, RE, Italy

Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia; 🇮🇹 Reggio Emilia, RE, 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

Azienda Sociosanitaria ASL 1 ,Imperia; 🇮🇹 Imperia, Italy

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