Randomized, Unicentric, Open, Controlled Clinical Trial, in Phase Iii, to Demonstrate the Effectiveness of Tocilizumab

Randomized, Unicentric, Open, Controlled Clinical Trial, in Phase Iii, to Demonstrate the Effectiveness of Tocilizumab Against Systemic Corticotherapy in Patients Admitted by Covid-19 With Bilateral Pneumonia and Poor Evolution

Randomized, open, single-center, controlled clinical trial, with 2 treatment arms that seeks to demonstrate the effectiveness of tocilizumab against systemic corticosteroids, both treatments added to supportive treatment in patients admitted for COVID-19 with bilateral pneumonia and poor evolution

Study Overview

• Status: Active, not recruiting
• Conditions: COVID-19 Pneumonia
• Intervention / Treatment: Drug: Tociliziumab group; Drug: Methylprednisolone group

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Spain
  • Guipuzcoa
    • San Sebastián, Guipuzcoa, Spain, 20014
      • Clinical Research Platform Biodonostia Health Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• 1) Patient over 18 years old
• 2) Ability to grant consent
• 3) Bilateral pneumonia produced by SARS-CoV-2 without response in 48-72 hours after starting the treatment used according to the local protocol. This is defined as persistence of fever (above 37.5ºC without another focus) and respiratory worsening (more dyspnea and / or more cough and / or oxygen therapy at increasing doses and / or worsening of the degree of respiratory distress according to the PaO2 / FiO2 ratio in categories "mild, moderate or severe") or absence of improvement compared to the previous state
• 4) Persistently elevated inflammatory markers, among which the following must be met: ferritin greater than 1000 ng / mL and / or D-dimer greater than 1500 ng / mL and / or IL-6 greater than 40 pg / mL [35-37], and / or CRP above 150 (mg / L) or having doubled the CRP provided it was above 50. Since this is what is included within the definition of "inflammatory phenotype"

Exclusion Criteria:

• 1) Embarazo y lactancia
• 2) Situación terminal o esperanza de vida inferior a 30 días a juicio del investigador
• 3) Alergia o intolerancia a alguno de los fármacos en estudio o a alguno de los excipientes de los preparados (p. ej polisorbato 80)
• 4) Interacción no tolerable de los fármacos del estudio con alguna medicación crónica imprescindible del paciente
• 5) Transaminasas elevadas por encima de cinco veces el límite superior de la normalidad
• 6) Severe neutropenia (<500 cells / mm3)
• 7) Plaquetopenia <50,000 / mm3
• 8) Sepsis (clinical suspicion of active infection at another level with a value on the qSOFA scale of two or more points) or septic shock (need for vasopressors to maintain a mean arterial pressure greater than or equal to 65 mmHg, with a lactate of more 2 mmol / L, despite adequate volume replacement
• 9) Another active infection at any level
• 10) Complicated diverticulitis or intestinal perforation
• 11) Renal failure with estimated glomerular filtration rate less than 30 mL / min
• 12) Hepatic failure (Child B onwards)
• 13) Previous use (during the acute process or as chronic medication for another reason) of medication with a potential effect in this phase of the disease (janus kinase inhibitors, interleukin 1 inhibitors, other immunosuppressants or immunomodulators that in the opinion of the investigator could have an effect on the disease based on pathophysiological criteria or on previous research or started in this same period). Clarification: The use of dexamethasone according to the RECOVERY study guideline or corticosteroid therapy at equivalent doses will not be included at this point.
• 14) Being included in another clinical trial
• 15) Patients who, due to their current situation, their baseline situation or other aspects, in the opinion of the researcher, are not considered candidates to enter the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tociliziumab group; Patients assigned to this arm will receive an intravenous dose of tocilizumab. Patients weighing 75 kg or more will receive 600 mg. Those weighing less than 75 kg will receive 400 mg.	Drug: Tociliziumab group; Tocilizumab is a humanized recombinant IgG1 monoclonal antibody to human interleukin-6 (IL-6) receptor, produced in Chinese hamster ovary cells by recombinant DNA technology.
Active Comparator: Metilprednisolone group; Patients in this arm will receive a daily intravenous dose of 250 mg methylprednisolone for 3 days.	Drug: Methylprednisolone group; Methylprednisolone belongs to a group of medicines called corticosteroids (it works at the cellular level by reducing the production of substances that cause inflammation or allergy).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory situation at 24 hours, 3 and 7 days based on the PaO2 / FiO2 ratio that graduates respiratory distress into mild (200-300), moderate (100-200) and severe (<100).	Quantitative variable that will be analyzed as qualitative (better, worse) based on whether there is a change in the graduation described above.	7 days
Immune hyperactivation situation: LDH, D-dimer and ferritin value at 24 hours, 3 and 7 days. Each one is a quantitative variable.	They will be measured as such and also qualitatively (worse, better) independently and together. A worsening of 2 of the 3 variables will be considered "worse"; "Better" if there is improvement in 2 of the 3.	7 days
Mechanical ventilation: qualitative variable (yes or no)		7 days
Combined variable of variables i, iii and in-hospital mortality (this is understood to be: respiratory deterioration or need for mechanical ventilation or in-hospital death)		7 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of patients admitted to the ICU	10 months
Time to admission to the ICU (from the beginning of the trial and from the beginning of the picture)	10 months
Time to the start of mechanical ventilation (from the start of the trial and from the start of the picture)	10 months
Time of admission to ICU	10 months
Total admission time	10 months
In-hospital mortality	10 months
Mortality at 30 and 60 days	60 days
Respiratory situation at 30 and 60 days according to pulse oximetric O2 saturation, respiratory rate and presence of dyspnea and NYHA grade.	10 months
Documented nosocomial infections	10 months

Collaborators and Investigators

• Sponsor: Asociacion Instituto Biodonostia

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2020
• Primary Completion (Actual): July 31, 2021
• Study Completion (Anticipated): October 31, 2021

Study Registration Dates

• First Submitted: August 9, 2021
• First Submitted That Met QC Criteria: August 11, 2021
• First Posted (Actual): August 12, 2021

Study Record Updates

• Last Update Posted (Actual): August 12, 2021
• Last Update Submitted That Met QC Criteria: August 11, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Lung Diseases; COVID-19; Pneumonia; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: TOCICOVID

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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