Immunoregulatory Therapy for 2019-nCoV-induced Severe Pneumonia Patients
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 120
- 主要终点
- lung injury score
研究概览
简要总结
Sepsis, including viral infections, are major causes of death worldwide. Studies show that in 2017, the number of sepsis patients worldwide reached as high as 48.9 million, of which 11 million patients died. Studies in China also showed that more than 1 million patients died of sepsis in 2015. Previous studies have suggested that sepsis are often secondary to excessive inflammatory response syndrome. However, treatment measures targeting excessive inflammatory response failed to effectively improve the prognosis of patients. PD-1 and PD-L1 are key mediators in T cell depletion in sepsis patients. Therefore, the investigators try to performe a clinical research to investigate the efficacy of PD-1 and thymosin in patients with severe pneumonia associated with lymphocytopenia in 2019 novel coronavirus infection.
详细描述
Sepsis, including viral infections, are major causes of death worldwide. Studies show that in 2017, the number of sepsis patients worldwide reached as high as 48.9 million, of which eleven million patients died. Studies in China also showed that more than one million patients died of sepsis in 2015. Therefore, how to effectively reduce the mortality of patients with sepsis has become a focus of clinical and basic research.
Previous studies have suggested that sepsis are often secondary to excessive inflammatory response syndrome. However, treatment measures targeting excessive inflammatory response failed to effectively improve the prognosis of patients. The reason is that sepsis-related immune dysfunction can increase the risk of secondary infection and even affect the fatality rate.
The immune checkpoint pathway is the endogenous component of the immune system, which is responsible for checking the immune response and keeping it in a normal physiological state. Tumor cells can evade host recognition through this pathway. One of these immunocheckpoint pathways is the PD-1 and PD-L1 pathways. PD-1 is a receptor expressed on the surface of T cells and ACTS as a negative regulator of T cell function. Monoclonal antibody blocking the activity of PD-1 can successfully reduce tumor load and has been widely used in the clinical treatment of various tumors.
The immune imbalance in patients with sepsis has many similarities tumors. PD-1 and PD-L1 are key mediators in T cell depletion in sepsis patients. Animal models have shown that blocking PD-1 or PD-L1 can prevent T cell death, regulate cytokine production, reduce organ dysfunction and reduce death in sepsis. Previous study showed the clinical safety of anti-PD-1 antibody in sepsis patients through randomized, placebo-controlled trials.
Thymosin has also been proved to regulate cellular immunity in sepsis patients. Some studies have shown that thymosin can significantly reduce the mortality of sepsis patients. At present, phase III clinical research is in progress to further clarify the role of thymosin in patients with sepsis. The purpose of this study was to investigate the efficacy of PD-1 and thymosin in patients with severe pneumonia associated with lymphocytopenia in 2019 novel coronavirus infection.
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
- Single (Participant)
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
- •Adult SARI patients with 2019-ncov infection confirmed by PCR;
- •Absolute value of lymphocytes <
- •Severe respiratory failure within 48 hours and requires admission to ICU. (severe respiratory failure was defined as PaO2/FiO2 < 200 mmHg and was supported by positive pressure mechanical ventilation (including non-invasive and invasive mechanical ventilation, PEEP>=5cmH2O))
排除标准
- •Allergic to experimental drugs
- •The underlying disease is very serious and the expected survival time is less than 6 months (such as advanced malignant tumor);
- •COPD or end-stage lung disease requires home oxygen therapy
- •Expected survival time not exceeding 48 hours
- •Participated in other clinical intervention trials within the last 3 months
- •Autoimmune diseases
- •A history of organ, bone marrow or hematopoietic stem cell transplantation
- •Received radiotherapy and chemotherapy for malignant tumor within 6 months
- •11.HIV infected patients or diagnosed with acquired immunodeficiency within the past year (CD4 T cells <=200/mm3)
- •Patients receiving anti-hcv treatment 13.90 days of retinal detachment or eye surgery
- •Permanent blindness in one eye
- •History of iritis, endophthalmitis, scleral inflammation or retinitis
- •The competent physician considered it inappropriate to participate in the study
研究组 & 干预措施
PD-1 group
Anti-PD-1 antibody, 200mg, IV, one time
干预措施: PD-1 blocking antibody+standard treatment (Drug)
thymosin group
Thymosin, 1.6 mg sc qd, last for 5 days
干预措施: Thymosin+standard treatment (Drug)
control group
stand treatment
干预措施: standard treatment (Other)
结局指标
主要结局
lung injury score
时间窗: 7 days
proportion of lung injury score decreased 1 or more points
次要结局
- serum level of CRP, PCT and IL-6(3, 7 and 14 days)
- absolute lymphocyte counts(7, 14 and 28 days)
- SOFA score(7 days)
- all cause mortality rate(28 days)
- ventilation free days(28 days)
- ICU free days(up to 28 days)
研究者
Jianfeng Xie
Director Assistant of ICU
Southeast University, China