Clinical Trial of the Use of Tocilizumab for Treatment of SARS-CoV-2 Infection (COVID-19) (TOCOVID)

Pilot, Randomized, Multicenter, Open-label Clinical Trial of the Use of Tocilizumab for Treatment of SARS-CoV-2 Infection (COVID-19)

COVID-19 is a respiratory disease caused by the new coronavirus (SARS-CoV-2) and causes considerable morbidity and mortality.

Currently, there is no vaccine or therapeutic agent to prevent and treat a SARS-CoV-2 infection. This clinical trial is designed to evaluate the use of Tocilizumab in combination with hydroxychloroquine and azithromycin for the treatment of hospitalized adult patients with COVID-19.

Study Overview

• Status: Recruiting
• Conditions: COVID-19
• Intervention / Treatment: Drug: Tocilizumab; Drug: Hydroxychloroquine; Drug: Azithromycin

• Study Type: Interventional
• Enrollment (Anticipated): 276
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Pere Domingo, MD, PhD; Email: pdomingo@santpau.cat

Study Locations

• Spain
  • Barcelona, Spain
    • Recruiting
    • Hospital del Mar
    • Contact: Juan Pablo Horcajada
  • Barcelona, Spain
    • Recruiting
    • Hospital de La Santa Creu I Sant Pau
    • Contact: Pere Domingo, MD, PhD; Email: pdomingo@santpau.cat
    • Principal Investigator: Pere Domingo, MD, PhD
  • Barcelona, Spain
    • Recruiting
    • Hospital Sant Joan Despí
    • Contact: Ana Coloma
  • Madrid, Spain
    • Recruiting
    • Hospital Clinico San Carlos
    • Contact: Vicente Estrada
  • Asturias
    • Oviedo, Asturias, Spain
      • Recruiting
      • Hospital Universitario Central de Asturias
      • Contact: Victor Asensi
  • Valencia
    • Alicante, Valencia, Spain
      • Recruiting
      • Hospital General Universitario de Alicante
    • Elche, Valencia, Spain
      • Recruiting
      • Hospital General Universitario de Elche
      • Contact: Felix Gutierrez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject (or authorized legal representative) who can provide written informed consent before beginning any study procedure.
• Understand and agree to abide by the study procedures.
• Adult #18 years of age at the time of inclusion in the study.
• Confirmation of SARS-CoV-2 infection by a microbiological test performed before randomization, no longer than 72 hours.
• Severity 3-4 according to the WHO 7-point ordinal scale.

Exclusion Criteria:

• ALT / AST> 5 times the normal limit
• Stage 4 chronic kidney disease (GFR <30) or requiring dialysis.
• Presence of comorbidities that imply a poor prognosis (according to clinical judgment).
• Advanced dementia.
• Pregnancy or breastfeeding.
• Anticipation of transfer to another center in the 12 hours at the beginning of the study.
• Allergy to study medication.
• Serious or active bacterial infections or documented sepsis by pathogens other than SARS-CoV-2.
• Streptococcus pneumoniae antigenuria positive before study start.
• Neutropenia <500 / mm3.
• Thrombocytopenia <100,000 / mm3.
• History of diverticulosis.
• Ongoing skin infection (eg, pyodermitis).
• Transplanted patient under immunosuppressive treatment.
• Previous evidence of latent untreated tuberculosis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; Early administration of tocilizumab associated with hydroxychloroquine and azithromycin.	Drug: Tocilizumab; 162 mg sc x 2 doses + tocilizumab 162mg sc x 2 doses at 12 hours (day 1); Drug: Hydroxychloroquine; 400 mg / 12h v.o. day 1 followed by 200 mg / 12h v.o. for 6 days (7 days in total); Drug: Azithromycin; 500 mg / day v.o. for 3 days
Active Comparator: Control; Treatment of SARS-COV-2 (COVID-19) infection with hydroxychloroquine and azithromycin.	Drug: Hydroxychloroquine; 400 mg / 12h v.o. day 1 followed by 200 mg / 12h v.o. for 6 days (7 days in total); Drug: Azithromycin; 500 mg / day v.o. for 3 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
In-hospital mortality	Through hospitalization, an average of 2 weeks
Need for mechanical ventilation in the Intensive Care Unit	Through hospitalization, an average of 2 weeks

Collaborators and Investigators

• Sponsor: Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau
• Collaborators: Instituto de Salud Carlos III

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2020
• Primary Completion (Anticipated): June 1, 2021
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: March 31, 2020
• First Submitted That Met QC Criteria: April 1, 2020
• First Posted (Actual): April 2, 2020

Study Record Updates

• Last Update Posted (Actual): May 6, 2021
• Last Update Submitted That Met QC Criteria: May 3, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Tocilizumab
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Azithromycin; Hydroxychloroquine
• Other Study ID Numbers: IIBSP-COV-2020-23

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No