The Efficacy and Safety of Thalidomide Combined With Low-dose Hormones in the Treatment of Severe COVID-19

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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COVID-19 Thalidomide

Intervention / Treatment
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* Drug: placebo
* Drug: Thalidomide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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; Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Control group<br>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. | Drug: placebo<br>* 100mg/d，qn，for 14 days.<br>|
| Experimental: Thalidomide group<br>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. | Drug: Thalidomide<br>* 100mg/d，qn，for 14 days.<br>* Other names: fanyingting;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Clinical Improvement (TTCI) | 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. | up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical status | Clinical status, assessed by the ordinal scale at fixed time points | 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 mechanical ventilation |  | up to 28 days | 
| Duration (days) of extracorporeal membrane oxygenation |  | up to 28 days | 
| Duration (days) of supplemental oxygenation |  | up to 28 days | 
| Length of hospital stay (days) |  | 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 | 
| 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 |