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

COVID-19 Thalidomide Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04273529
• Other study ID #: 20200214-COVID-19-M-T
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: February 20, 2020
• Est. completion date: June 30, 2020

Study information

• Verified date: February 2020
• Source: First Affiliated Hospital of Wenzhou Medical University
• Contact: Jinglin Xia, MD
• Phone: 0577-55578166
• Email: xiajinglin[@]fudan.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: June 30, 2020
• Est. primary completion date: May 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19 Thalidomide
• Pneumonia

Intervention

Drug:
• thalidomide
100mg,po,qn,for 14 days.
• placebo
100mg,po,qn,for 14 days.

Locations

Country	Name	City	State
n/a

Sponsors (3)

Lead Sponsor	Collaborator
First Affiliated Hospital of Wenzhou Medical University	Second Affiliated Hospital of Wenzhou Medical University, Wenzhou Central Hospital

References & Publications (8)

Bartlett JB, Dredge K, Dalgleish AG. The evolution of thalidomide and its IMiD derivatives as anticancer agents. Nat Rev Cancer. 2004 Apr;4(4):314-22. doi: 10.1038/nrc1323. Review. — View Citation

Jin YH, Cai L, Cheng ZS, Cheng H, Deng T, Fan YP, Fang C, Huang D, Huang LQ, Huang Q, Han Y, Hu B, Hu F, Li BH, Li YR, Liang K, Lin LK, Luo LS, Ma J, Ma LL, Peng ZY, Pan YB, Pan ZY, Ren XQ, Sun HM, Wang Y, Wang YY, Weng H, Wei CJ, Wu DF, Xia J, Xiong Y, Xu HB, Yao XM, Yuan YF, Ye TS, Zhang XC, Zhang YW, Zhang YG, Zhang HM, Zhao Y, Zhao MJ, Zi H, Zeng XT, Wang YY, Wang XH; , for the Zhongnan Hospital of Wuhan University Novel Coronavirus Management and Research Team, Evidence-Based Medicine Chapter of China International Exchange and Promotive Association for Medical and Health Care (CPAM). A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version). Mil Med Res. 2020 Feb 6;7(1):4. doi: 10.1186/s40779-020-0233-6. — View Citation

Kwon HY, Han YJ, Im JH, Baek JH, Lee JS. Two cases of immune reconstitution inflammatory syndrome in HIV patients treated with thalidomide. Int J STD AIDS. 2019 Oct;30(11):1131-1135. doi: 10.1177/0956462419847297. Epub 2019 Sep 19. — View Citation

Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet. 2020 Feb 7. pii: S0140-6736(20)30317-2. doi: 10.1016/S0140-6736(20)30317-2. [Epub ahead of print] — View Citation

Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, Wang B, Xiang H, Cheng Z, Xiong Y, Zhao Y, Li Y, Wang X, Peng Z. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020 Feb 7. doi: 10.1001/jama.2020.1585. [Epub ahead of print] — View Citation

Wen H, Ma H, Cai Q, Lin S, Lei X, He B, Wu S, Wang Z, Gao Y, Liu W, Liu W, Tao Q, Long Z, Yan M, Li D, Kelley KW, Yang Y, Huang H, Liu Q. Recurrent ECSIT mutation encoding V140A triggers hyperinflammation and promotes hemophagocytic syndrome in extranodal NK/T cell lymphoma. Nat Med. 2018 Feb;24(2):154-164. doi: 10.1038/nm.4456. Epub 2018 Jan 1. — View Citation

Zhao L, Xiao K, Wang H, Wang Z, Sun L, Zhang F, Zhang X, Tang F, He W. Thalidomide has a therapeutic effect on interstitial lung fibrosis: evidence from in vitro and in vivo studies. Clin Exp Immunol. 2009 Aug;157(2):310-5. doi: 10.1111/j.1365-2249.2009.03962.x. — View Citation

Zhu H, Shi X, Ju D, Huang H, Wei W, Dong X. Anti-inflammatory effect of thalidomide on H1N1 influenza virus-induced pulmonary injury in mice. Inflammation. 2014 Dec;37(6):2091-8. doi: 10.1007/s10753-014-9943-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Time to cough reported as mild or absent	in those with cough at enrolment rated severe or moderate	up to 28 days
Other	Respiratory improvement time	patients with moderate / severe dyspnea when enrolled	up to 28 days
Other	Frequency of requirement for supplemental oxygen or non-invasive ventilation		up to 28 days
Other	Time to 2019-nCoV RT-PCR negative in upper respiratory tract specimen		up to 28 days
Other	Change (reduction) in 2019-nCoV viral load in upper respiratory tract specimen as assessed by area under viral load curve		up to 28 days
Other	Frequency of requirement for mechanical ventilation		up to 28 days
Other	Frequency of serious adverse events		up to 28 days
Other	Serum TNF-a, IL-1ß, IL-2, IL-6, IL-7, IL-10, GSCF, IP10,MCP1, MIP1a and other cytokine expression levels before and after treatment		up to 28 days
Primary	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	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
Secondary	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
Secondary	Time to defervescence	in those with fever at enrolment	up to 28 days