Safety and Effectiveness Observational Study of Anti IL-6 Tocilizumab in Hospital Admitted Patients With Severe COVID-19 Pneumonia.
试验速览
- 阶段
- 不适用
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- 28-day mortality
研究概览
简要总结
Retrospective observational cohort study to evaluate the safety and effectiveness of tocilizumab in the treatment of severe COVID-19 pneumonia
详细描述
Since the appearence of the disease today known as COVID-19 there has been multiple interventions to try to gain knowledge on the subject and obtain a benefitial effect treating this condition.
Tocilizumab, a monoclonal antibody targeting IL-6 receptor has arised as an alternative for the treament of COVID-19 pneumonia.
It is a drug used for the treatment of rhemautoid arthritis and other autoimmune diseases as well as approved in recent years for the treatment of the cytokine release syndrome (CRS) in CAR-T therapy.
It is based in this last premise that the benefitial effect on COVID-19 pneumonia has been sought of. According to investigation into the physiopathology of the virus, it is supposed to trigger the inflamattory cascade that generates damage to lungs and creates the most severe cases of the disease. These findings could imply that tocilizumab may serve to interrupt this cytokine storm and prevent the progression of the disease.
The aim of the study is to evaluate the effectiveness and safety of tocilizumab in the treatment of severe cases of COVID-19. For that purpose, an observational retrospective cohort study has been designed comparing two populations that share the same indication for the treatment with tocilizumab. One having received the drug and the other in a close previous period of time that has not received it because of lack of availability or generalisation of its use. Mortality will be assesed as well as other variables such as need for mechanical ventilation and adverse effects of tocilizumab.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Hospital admitted patients with severe COVID-19 pneumonia (Individuals who have SpO2 <94% on room air at sea level, a ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) <300 mm Hg, respiratory frequency >30 breaths/min, or lung infiltrates >50%).
- •Confirmed diagnosis of Covid-19 through qualitative polymerase-reverse transcriptase (qRT-PCR -GeneDX Co, Ltd o similar) or antigen rapid test.
- •Patients who received tocilizumab or shared the same indication but did not received it (same period of time or previous close period) that:
- •Progress in the requirement of supplemental oxygen (over 3L/m) and/or use of non-rebreathing mask with 8L/m or more to mantain a Sp02>= 94%.
- •* Active inflammatory state defined as persistent fever > 38°C (defined as 2 or more measurements in a 24-hour period from hospital admission) despite the use of dexamethasone in the previous 48 hours OR C reactive Protein > 50 mg /dL OR D Dimer > 1000 ng/mL.
排除标准
- •Asymptomatic, mild or moderate COVID-19 disease.
- •Patients with some type of immunosupression (HIV, use of immunomodulatory drugs, organ-trasplant receipt patients)
- •Pregnant or breast-feeding
- •Patients with augmented risk of bowel perforation (history of diverticulitis or bowel surgery in the three months prior to the study entrance date)
- •Known severe allergic reactions to TCZ
- •Suspected active bacterial, fungal, viral, or other infection (besides COVID-19)
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 5 x upper limit of normal (ULN) at screening
- •Absolute neutrophil count (ANC) < 1000/mL at screening
- •Platelet count < 50,000/mL at screening
- •Positive Hepatitis B Surface (HbS) antigen
- •Procalcitonine > 0,5 ng/mL
- •Day of symptom onset before day 7 or after day 12
- •Patients with dementia
- •Patients non eligible to progress to mechanical ventilation because of frailty/comorbidites according to medical decision.
研究组 & 干预措施
Tocilizumab
Group that received tocilizumab (8mg/kg, maximum dose 800 mg, only once) while being admitted with severe COVID-19 pneumonia.
干预措施: Tocilizumab (Drug)
结局指标
主要结局
28-day mortality
时间窗: 28 days from hospital admission
28-day mortality
Percentage of patients in invasive mechanical ventilation at day 28
时间窗: 28 days from hospital admission
Percentage of patients that received invasive mechanical ventilation at day 28 following hospital admission.
Clinical status during follow-up at 28th day
时间窗: 28th day from hospital admission
Ordinal outcome with seven mutually exclusive categories to describe the patient's clinical status during follow-up. The six categories are: (1) Discharged or ready for discharge; (2) Admitted to non-ICU ward without oxygen; (3) admitted to non-ICU ward but requiring supplemental oxygen; (4) admitted to ICU or non ICU ward requiring high flow nasal canula or other non invasive mechanical ventilation; (5) admitted to ICU ward requiring invasive mechanical ventilation (6) admitted to ICU ward requiring extracorporeal membrane oxygenation or invasive mechanical ventilation plus other vital organ support; (7) death
次要结局
- Time to hospital discharge(Up to 60 days)
- Percentage of patients in invasive mechanical ventilation at day 14 and 21(Days 14 and 21)
- Percentage of patients with need of tracheostomy at day 28 of hospital admission(28th day from hospital admission)
- Mortality rate(Days 14 and 21)
- Days of ICU admission(Up to 60 days)
- Percentage of patients with hospital discharge at day 7, 14, 21 and 28(Days 7, 14, 21 and 28)
- Percentage of patients admitted to ICU-ward at day 28(28th day from hospital admission)
- Time to Improvement of at Least 2 Categories Relative to Baseline on a 7-Category Ordinal Scale of Clinical Status(Up to 60 days)
- Time to mechanical ventilation from hospital admission(Up to 28 days)
- Time to ICU discharge from hospital admission(Up to 60 days)
- Percentage of patients with adverse effects / serious adverse effects(Up to 28 days)
- Percentage of superimposed infections(28th day from hospital admission)
研究者
ANACLARA MURUJOSA
MD
Hospital Italiano de Buenos Aires