Randomized, open, single-center, controlled clinical trial, with 2 treatment arms thatseeks to demonstrate the effectiveness of tocilizumab against systemic corticosteroids,both treatments added to supportive treatment in patients admitted for COVID-19 withbilateral pneumonia and poor evolution
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.
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).
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
Clinical Research Platform Biodonostia Health Research Institute
San Sebastián, Guipuzcoa, Spain