Comparison of Tocilizumab Versus Tocilizumab/Infliximab in Patients With COVID-19-associated Cytokine Storm Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 153
- 试验地点
- 1
- 主要终点
- Time to improvement in oxygenation
研究概览
简要总结
Since the end of 2019, Egypt and the whole world have been suffering from the Coronavirus Disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). According to the World Health Organization (WHO), since the emergence of this new pandemic, there have been more than 97 million confirmed cases of COVID-19 patients and two million death globally; around 160 thousand of these cases are in Egypt.
Tocilizumab play role among the unique therapeutic alternatives for the management of cytokine release syndrome (CRS), a life-threatening complication of chimeric antigen receptor (CAR) - T cell therapy. CRS occurs as a result of uncontrolled immune activation with release of pro-inflammatory cytokines and chemokines. Up till now, clinical trial and expertise with tocilizumab in COVID-19 patients has been limited. Despite preliminary encouraging results, recent studies suffered from limitations such as the absence of consistent treatment outline, a short post-treatment follow-up, and the absence of a comparison group.
A recent study discussed the possible beneficial effect of tumor necrosis factor (TNF) inhibitors in severe COVID-19. Specifically, TNF may aggravate lymphopenia through direct killing via TNF/TNFR1 signaling in T cells, and T cell dysfunction reveals an important yet underestimated target for immunomodulatory therapeutic approaches. Accordingly, anti-TNF may be considered as an encouraging therapeutic option in severe COVID-19.
These promising clinical findings encouraged us to use infliximab (IFX), a chimeric monoclonal anti-TNF antibody, as an experimental therapy in patients with moderate and severe COVID-19 in the absence of IBD.
In this study, we compare the outcomes of a large cohort of patients with moderate and severe COVID-19 pneumonia treated with tocilizumab in addition to standard management, with those of concomitantly hospitalized patients who received infliximab and tocilizumab in addition to standard management.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Other
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-65 years.
- •Able to provide informed consent.
- •Patients hospitalized with pneumonia proved by chest X-ray or CT scan.
- •Confirmed infection with COVID-2019 using RT-PCR or strongly suspected to be infected with pending confirmation studies.
- •Hyper-inflammation defined as elevation in either C-reactive protein (CRP, ≥ 100 mg/L, normal values <6 mg/L) or ferritin (≥ 900 ng/mL, normal value <400 ng/mL), in the presence of increased lactate dehydrogenase (LDH, >220 U/L).
- •And at least one of the following:
- •Respiratory frequency ≥30/min.
- •Blood oxygen saturation ≤93% on room air (RA).
- •Partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) <300 [18].
- •Worsening of lung involvement, defined as an increase in number and/or extension of pulmonary areas of consolidation, need for increased FiO2 to maintain stable O2 saturation, or worsening O2 saturation of >3% with stable FiO2.
排除标准
- •Evidence of concomitant bacterial infection.
- •Concomitant use of other immunosuppressive biologic drugs.
- •Baseline elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 5-fold the upper limit of the normal range.
- •Treatment with any TNFα inhibitor in the past 30 days.
- •Known hypersensitivity to any TNFα inhibitor, murine proteins, or any component of the formulation.
- •Known or suspected active tuberculosis (TB) or a history of incompletely treated or latent TB.
- •Serious co-morbidity, including:
- •Myocardial infarction (within last month).
- •Moderate or severe heart failure (New York Heart Association (NYHA) class III or IV).
- •Hepatic patients child Pugh class C.
研究组 & 干预措施
Group 1
Moderate and severe patients who were infected with SARS-CoV-2 and received treatment with tocilizumab in addition to standard management.
干预措施: Tocilizumab (Drug)
Group 2
Moderate and severe patients who were infected with SARS-CoV-2 and received treatment with infliximab and tocilizumab in addition to standard management.
干预措施: Tocilizumab (Drug)
Group 2
Moderate and severe patients who were infected with SARS-CoV-2 and received treatment with infliximab and tocilizumab in addition to standard management.
干预措施: Infliximab (Drug)
结局指标
主要结局
Time to improvement in oxygenation
时间窗: 48 hours
Increase in SpO2/FiO2 of 50 or greater compared to the baseline SpO2/FiO2
Patients' clinical status improvement using six category scale
时间窗: Two weeks
The categories were defined as follows: 1) patient discharged, 2) hospitalization not requiring supplemental oxygen, 3) hospitalization requiring supplemental low-flow oxygen, 4) hospitalization requiring high-flow supplemental oxygen, 5) hospitalization requiring invasive mechanical ventilation, 6) death.
Duration of hospitalization
时间窗: Two weeks
Total admission period
Mortality rate
时间窗: Two weeks
Death during hospitalization
次要结局
- Incidence of invasive mechanical ventilation(Two weeks)
- Monitoring of adverse events(Two weeks)
- Duration of non-invasive mechanical ventilation(Two weeks)
- Incidence of non-invasive mechanical ventilation(Two weeks)
- Occurrence of cardiovascular events(Two weeks)
- Duration of invasive mechanical ventilation(Two weeks)
- Occurrence of Secondary infections(Two weeks)
研究者
Neven Sarhan
Lecturer at Faculty of Pharmacy
Misr International University