The Efficacy and Safety of Thalidomide Combined With Low-dose Hormones in the Treatment of Severe New Coronavirus (COVID-19) Pneumonia: a Prospective, Multicenter, Randomized, Double-blind, Placebo, Parallel Controlled Clinical Study
试验速览
- 阶段
- 2 期
- 入组人数
- 40
- 主要终点
- Time to Clinical Improvement (TTCI)
研究概览
简要总结
In view of the fact that there is currently no effective antiviral therapy, the prevention or treatment of lung injury caused by COVID-19 can be an alternative target for current treatment. Patients with severe COVID-19 have rapid disease progression and high mortality. There is currently no effective treatment method, which may be related to the excessive immune response caused by cytokine storm. This study will evaluate thalidomide combined with low-dose hormone adjuvant therapy for severe COVID-19 Patient effectiveness and safety.
详细描述
Thalidomide has been clinically reported, and combined with antiviral drugs and other conventional treatments have achieved good results in the treatment of severe H1N1, especially after the death of a young severe patient. After the addition of thalidomide, the reported 35 patients did not Deaths. Subsequent basic research at Fudan University confirmed that thalidomide can treat H1N1 lung injury. And think that the combination with antiviral drugs may be a better alternative strategy for H1N1 before the vaccine is successfully developed.
In view of the fact that there is currently no effective antiviral therapy, the prevention or treatment of lung injury caused by COVID-19 can be an alternative target for current treatment. Patients with severe COVID-19 have rapid disease progression and high mortality. There is currently no effective treatment method, which may be related to the excessive immune response caused by cytokine storm.It has been reported that the combined use of thalidomide and dexamethasone can effectively inhibit NK / T-cell lymphoma combined with ECSIT V140A mutation of hematophilic syndrome. The AIDS immune reconstitution syndrome (IRIS) is also an abnormal inflammatory response in nature. It has been reported that thalidomide as an immunomodulatory agent for the treatment of IRIS is effective. This study will evaluate thalidomide combined with low-dose hormone adjuvant therapy for severe COVID-19 Patient effectiveness and safety.
Although the death rate of COVID-19 infected persons is not high, their rapid infectiousness and the lack of effective antiviral treatment currently have become the focus of the national and international epidemic. Thalidomide has been available for more than sixty years, and has been widely used in clinical applications. It has been proved to be safe and effective in IPF, severe H1N1 influenza lung injury and paraquat poisoning lung injury, and the mechanism of anti-inflammatory and anti-fibrosis is relatively clear. As the current research on COVID-19 at home and abroad mainly focuses on the exploration of antiviral efficacy, this study intends to find another way to start with host treatment in the case that antiviral is difficult to overcome in the short term, in order to control or relieve lung inflammation caused by the virus To improve lung function.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Age ≥18 years;
- •The laboratory (RT-PCR) confirmed the diagnosis of severe patients infected with CoVID-19 (refer to the fifth edition of the Chinese diagnosis and treatment guideline for trial); the diagnosis of new coronavirus pneumonia was confirmed, and any of the following: 1) Respiratory distress, breathing ≥30 beats / min; 2) In the resting state, the oxygen saturation is ≤93%; 3) Arterial blood oxygen partial pressure / oxygen concentration ≤300mmHg
- •The diagnosis is less than or equal to 12 days;
排除标准
- •Severe liver disease (such as Child Pugh score ≥ C, AST> 5 times the upper limit); severe renal dysfunction (the glomerulus is 30ml / min / 1.73m2 or less)
- •Pregnancy or breastfeeding or positive pregnancy test;
- •In the 30 days before the screening assessment, have taken any experimental treatment drugs for CoVID-19 (including off-label, informed consent use or trial-related);
- •Those with a history of thromboembolism, except for those caused by PICC.
研究组 & 干预措施
Control group
α-interferon： nebulized inhalation, 5 million U or equivalent dose added 2ml of sterile water for injection, 2 times a day, for 7 days； Abidol, 200mg / time, 3 times a day, for 7 days; Methylprednisolone： 40mg, q12h， for 5 days. placebo：100mg/d，qn，for 14 days.
干预措施: placebo (Drug)
Thalidomide group
α-interferon： nebulized inhalation, 5 million U or equivalent dose added 2ml of sterile water for injection, 2 times a day, for 7 days； Abidol, 200mg / time, 3 times a day, for 7 days; Methylprednisolone： 40mg, q12h， for 5 days. thalidomide：100mg/d，qn，for 14 days.
干预措施: Thalidomide (Drug)
结局指标
主要结局
Time to Clinical Improvement (TTCI)
时间窗: up to 28 days
TTCI is defined as the time (in days) from initiation of study treatment (active or placebo) until a decline of two categories from admission status on a six-category ordinal scale of clinical status which ranges from 1 (discharged) to 6 (death). Six-category ordinal scale: 6. Death; 5. ICU, requiring ECMO and/or IMV; 4. ICU/hospitalization, requiring NIV/ HFNC therapy; 3. Hospitalization, requiring supplemental oxygen (but not NIV/ HFNC); 2. Hospitalization, not requiring supplemental oxygen; 1. Hospital discharge. Abbreviation: IMV, invasive mechanical ventilation; NIV, non-invasive mechanical ventilation; HFNC, High-flow nasal cannula.
次要结局
- Duration (days) of mechanical ventilation(up to 28 days)
- Time to 2019-nCoV RT-PCR negativity in upper and lower respiratory tract specimens(up to 28 days)
- Change (reduction) in 2019-nCoV viral load in upper and lower respiratory tract specimens as assessed by area under viral load curve.(up to 28 days)
- Frequency of serious adverse drug events(up to 28 days)
- Clinical status(days 7, 14, 21, and 28)
- Time to Hospital Discharge OR NEWS2 (National Early Warning Score 2) of ≤ 2 maintained for 24 hours(up to 28 days)
- All cause mortality(up to 28 days)
- Duration (days) of extracorporeal membrane oxygenation(up to 28 days)
- Serum TNF-α, IL-1β, IL-2, IL-6, IL-7, IL-10, GSCF, IP10#MCP1, MIP1α and other cytokine expression levels before and after treatment(up to 28 days)
- Length of hospital stay (days)(up to 28 days)
- Duration (days) of supplemental oxygenation(up to 28 days)