Efficacy of Early Administration of Tocilizumab in COVID-19 Patients

NCT04346355 | Terminated Phase 2 DMC

• 2 other identifiers: RCT-TCZ-COVID-192020-001386-37
• Study Type: interventional
• Target: 126
• Locations: 1 country
• Sites: 25

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.

Conditions

COVID-19 Pneumonia

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• Death from any cause

  Two weeks from participants' allocation to study arm

• Tocilizumab toxicity

  Two weeks from participants' allocation to study arm

• 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

• Evaluate the progress of the PaO2 / FiO2 ratio

  Two weeks from participants' allocation to study arm

• Evaluate the trend over time of the lymphocyte count

  Two weeks from participants' allocation to study arm

Study Arms (2)

Experimental Arm

EXPERIMENTAL

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

Drug: Tocilizumab

Control Arm

OTHER

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

Drug: Tocilizumab

Interventions

Tocilizumab DRUG

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

Also known as: Standard of care

Control Arm; Experimental Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Azienda USL Reggio Emilia - IRCCS: lead

Study Sites (25)

Ospedale di Guastalla

Guastalla, RE, Italy

Location

Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia

Reggio Emilia, RE, 42122, Italy

Location

Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo

Alessandria, Italy

Location

Policlinico Sant'Orsola Malpighi

Bologna, Italy

Location

ASST Cremona

Cremona, Italy

Location

Azienda Ospedaliera S. Croce e Carle

Cuneo, Italy

Location

Azienda Ospedaliero Universitaria Ferrara

Ferrara, Italy

Location

Azienda Ospedaliero Universitaria Careggi

Florence, Italy

Location

Ospedale Evangelico Internazionale di Genova

Genova, Italy

Location

Azienda Sociosanitaria ASL 1 ,Imperia

Imperia, Italy

Location

Azienda Sociosanitaria ASL 5 La Spezia

La Spezia, Italy

Location

ASST Mantova - Ospedale Carlo Poma

Mantova, Italy

Location

IRCCS Istituto Auxologico Italiano Milano

Milan, Italy

Location

Azienda Ospedaliero-Universitaria "Maggiore della Carità" di Novara

Novara, Italy

Location

Ospedali Riuniti Padova Sud - ULSS 6 Euganea

Padua, Italy

Location

Azienda Ospedaliero-Universitaria Parma

Parma, Italy

Location

Azienda Unità Sanitaria Locale di Piacenza

Piacenza, Italy

Location

Azienda Ospedaliera Universitaria Pisana

Pisa, Italy

Location

AO Ordine Mauriziano di Torino

Torino, Italy

Location

ASST Bergamo Ovest -Treviglio

Treviglio, Italy

Location

AULSS 2 Marca Trevigiana

Treviso, Italy

Location

AULSS2 Marca Trevigiana - Ospedale Vittorio Veneto

Treviso, Italy

Location

AULSS 3 Serenissima Ospedale "Dell'Angelo"

Venezia, Italy

Location

Azienda Ospedaliera Universitaria Integrata di Verona

Verona, Italy

Location

IRCCS Sacro Cuore Don Calabria

Verona, Italy

Location

Related Publications (1)

• 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.

  PMID: 33080005 DERIVED

MeSH Terms

Interventions

tocilizumab; Standard of Care

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Carlo Salvarani, M.D.

  Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia

  STUDY DIRECTOR

• Massimo Costantini, Ph.D.

  Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2020
• First Posted: April 15, 2020
• Study Start: March 31, 2020
• Primary Completion: June 6, 2020
• Study Completion: June 6, 2020
• Last Updated: June 22, 2020

Record last verified: 2020-06

Locations

IT (25)