Clinical trial NCT04273529: The Efficacy and Safety of Thalidomide in the Adjuvant Treatment of Moderate New Coronavirus (COVID-19) Pneumonia
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: COVID-19 Thalidomide
Lead sponsor: First Affiliated Hospital of Wenzhou Medical University
Sponsor class: OTHER
Collaborators: name: Second Affiliated Hospital of Wenzhou Medical University
name: Wenzhou Central Hospital
First posted: 2020-02-18
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥18 years;
2. Laboratory (RT-PCR) diagnosis of common patients infected with COVID-19 (refer to the fifth edition of the Chinese Guidelines for Diagnosis and Treatment);
3. chest imaging confirmed lung damage;
4. The diagnosis is less than or equal to 8 days;

Exclusion Criteria:

1. 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)
2. Positive pregnancy or breastfeeding or pregnancy test;
3. 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);
4. Those with a history of thromboembolism, except for those caused by PICC.

Primary outcomes:
measure: Time to Clinical recoveryTime to Clinical Recovery (TTCR)
timeFrame: up to 28 days
Secondary outcomes:
measure: All cause mortality
timeFrame: up to 28 days
measure: Frequency of respiratory progression
timeFrame: up to 28 days
measure: Time to defervescence
timeFrame: up to 28 days
Other outcomes:
measure: Time to cough reported as mild or absent
timeFrame: up to 28 days
measure: Respiratory improvement time
timeFrame: up to 28 days
measure: Frequency of requirement for supplemental oxygen or non-invasive ventilation
timeFrame: up to 28 days
measure: Time to 2019-nCoV RT-PCR negative in upper respiratory tract specimen
timeFrame: up to 28 days
measure: Change (reduction) in 2019-nCoV viral load in upper respiratory tract specimen as assessed by area under viral load curve
timeFrame: up to 28 days
measure: Frequency of requirement for mechanical ventilation
timeFrame: up to 28 days
measure: Frequency of serious adverse events
timeFrame: up to 28 days
measure: 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
timeFrame: up to 28 days
Locations:
Study officials:
affiliation: First Affiliated Hospital of Wenzhou Medical University
name: Jinglin Xia, MD
role: PRINCIPAL_INVESTIGATOR
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