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
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- 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).
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Patient over 18 years old
- •Ability to grant consent
- •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
- •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
- •Since this is what is included within the definition of "inflammatory phenotype"
排除标准
- •Embarazo y lactancia
- •Situación terminal o esperanza de vida inferior a 30 días a juicio del investigador
- •Alergia o intolerancia a alguno de los fármacos en estudio o a alguno de los excipientes de los preparados (p. ej polisorbato 80)
- •Interacción no tolerable de los fármacos del estudio con alguna medicación crónica imprescindible del paciente
- •Transaminasas elevadas por encima de cinco veces el límite superior de la normalidad
- •Severe neutropenia (<500 cells / mm3)
- •Plaquetopenia <50,000 / mm3
- •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
- •Another active infection at any level
- •Complicated diverticulitis or intestinal perforation
- •Renal failure with estimated glomerular filtration rate less than 30 mL / min
- •Hepatic failure (Child B onwards)
- •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.
- •Being included in another clinical trial
- •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
研究组 & 干预措施
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.
干预措施: Tociliziumab group (Drug)
Metilprednisolone group
Patients in this arm will receive a daily intravenous dose of 250 mg methylprednisolone for 3 days.
干预措施: Methylprednisolone group (Drug)
结局指标
主要结局
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).
时间窗: 7 days
Quantitative variable that will be analyzed as qualitative (better, worse) based on whether there is a change in the graduation described above.
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)
时间窗: 7 days
Immune hyperactivation situation: LDH, D-dimer and ferritin value at 24 hours, 3 and 7 days. Each one is a quantitative variable.
时间窗: 7 days
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.
Mechanical ventilation: qualitative variable (yes or no)
时间窗: 7 days
次要结局
- Number of patients admitted to the ICU(10 months)
- In-hospital mortality(10 months)
- Documented nosocomial infections(10 months)
- Time to the start of mechanical ventilation (from the start of the trial and from the start of the picture)(10 months)
- Total admission time(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)
- Time of admission to ICU(10 months)
- Time to admission to the ICU (from the beginning of the trial and from the beginning of the picture)(10 months)