The Efficacy and Safety of Thalidomide in the Adjuvant Treatment of Moderate New Coronavirus (COVID-19) Pneumonia

Study Overview
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Brief Summary
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In December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia of unknown cause. In a short time, Chinese scientists had shared the genome information of a novel coronavirus (2019-nCoV) from these pneumonia patients and developed a real-time reverse transcription PCR (real time RT-PCR) diagnostic assay. 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. Thalidomide has anti-inflammatory, anti-fibrotic, anti-angiogenesis, and immune regulation effects. This study is the first Prospective, Multicenter, Randomized, Double-blind, Placebo, Parallel Controlled Clinical Study at home and abroad to use immunomodulators to treat patients with COVID-19 infection.

Detailed Description
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The new coronavirus (COVID-19) [1] belongs to the new beta coronavirus. Current research shows that it has 85% homology with bat SARS-like coronavirus (bat-SL-CoVZC45), but its genetic characteristics are similar to SARSr-CoV. There is a clear difference from MERSr-COV. Since December 2019, Wuhan City, Hubei Province has successively found multiple cases of patients with pneumonia infected by a new type of coronavirus. With the spread of the epidemic, as of 12:00 on February 12, 2020, a total of 44726 confirmed cases nationwide (Hubei Province) 33,366 cases, accounting for 74.6%), with 1,114 deaths (1068 cases in Hubei Province), and a mortality rate of 2.49% (3.20% in Hubei Province). 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. Thalidomide has anti-inflammatory, anti-fibrotic, anti-angiogenesis, and immune regulation effects. In the early clinical practice of treating severe A H1N1, it was clinically concerned, and combined with hormones and conventional treatment, and achieved good results. 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. This study is the first study at home and abroad to use immunomodulators to treat patients with COVID-19 infection. It is hoped that the patients can get out of the bitter sea as soon as possible and provide effective solutions for the country and society.

Official Title
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The Efficacy and Safety of Thalidomide in the Adjuvant Treatment of Moderate 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: thalidomide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years; Laboratory (RT-PCR) diagnosis of common patients infected with COVID-19 (refer to the fifth edition of the Chinese Guidelines for Diagnosis and Treatment); chest imaging confirmed lung damage; The diagnosis is less than or equal to 8 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) Positive pregnancy or breastfeeding or 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>placebo | Drug: placebo<br>* 100mg，po，qn，for 14 days.<br>|
| Experimental: Thalidomide group<br>thalidomide | Drug: thalidomide<br>* 100mg，po，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 recoveryTime to Clinical Recovery (TTCR) | TTCR is defined as the time (in hours) from initiation of study treatment (active or placebo) until normalisation of fever, respiratory rate, and oxygen saturation, and alleviation of cough, sustained for at least 72 hours. Normalisation and alleviation criteria: Fever - ≤36.6°C or -axilla, ≤37.2 °C oral or ≤37.8°C rectal or tympanic, Respiratory rate - ≤24/minute on room air, Oxygen saturation - >94% on room air, Cough - mild or absent on a patient reported scale of severe, moderate, mild, absent. | up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All cause mortality | baseline SpO2 during screening, PaO2/FiO2 <300mmHg or a respiratory rate ≥ 24 breaths per min without supplemental oxygen | up to 28 days | 
| Frequency of respiratory progression | Defined as SPO2≤ 94% on room air or PaO2/FiO2 <300mmHg and requirement for supplemental oxygen or more advanced ventilator support. | up to 28 days | 
| Time to defervescence | in those with fever at enrolment | up to 28 days |