The Efficacy and Safety of Thalidomide in the Adjuvant Treatment of Moderate New Coronavirus (COVID-19) Pneumonia
Primary Purpose
COVID-19 Thalidomide
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
thalidomide
placebo
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 Thalidomide
Eligibility Criteria
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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Experimental
Arm Label
Control group
Thalidomide group
Arm Description
placebo
thalidomide
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
All cause mortality
baseline SpO2 during screening, PaO2/FiO2 <300mmHg or a respiratory rate ≥ 24 breaths per min without supplemental oxygen
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.
Time to defervescence
in those with fever at enrolment
Full Information
NCT ID
NCT04273529
First Posted
February 14, 2020
Last Updated
February 19, 2020
Sponsor
First Affiliated Hospital of Wenzhou Medical University
Collaborators
Second Affiliated Hospital of Wenzhou Medical University, Wenzhou Central Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04273529
Brief Title
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
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Unknown status
Study Start Date
February 20, 2020 (Anticipated)
Primary Completion Date
May 30, 2020 (Anticipated)
Study Completion Date
June 30, 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
First Affiliated Hospital of Wenzhou Medical University
Collaborators
Second Affiliated Hospital of Wenzhou Medical University, Wenzhou Central Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19 Thalidomide
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control group
Arm Type
Placebo Comparator
Arm Description
placebo
Arm Title
Thalidomide group
Arm Type
Experimental
Arm Description
thalidomide
Intervention Type
Drug
Intervention Name(s)
thalidomide
Other Intervention Name(s)
fanyingting
Intervention Description
100mg,po,qn,for 14 days.
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
100mg,po,qn,for 14 days.
Primary Outcome Measure Information:
Title
Time to Clinical recoveryTime to Clinical Recovery (TTCR)
Description
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.
Time Frame
up to 28 days
Secondary Outcome Measure Information:
Title
All cause mortality
Description
baseline SpO2 during screening, PaO2/FiO2 <300mmHg or a respiratory rate ≥ 24 breaths per min without supplemental oxygen
Time Frame
up to 28 days
Title
Frequency of respiratory progression
Description
Defined as SPO2≤ 94% on room air or PaO2/FiO2 <300mmHg and requirement for supplemental oxygen or more advanced ventilator support.
Time Frame
up to 28 days
Title
Time to defervescence
Description
in those with fever at enrolment
Time Frame
up to 28 days
Other Pre-specified Outcome Measures:
Title
Time to cough reported as mild or absent
Description
in those with cough at enrolment rated severe or moderate
Time Frame
up to 28 days
Title
Respiratory improvement time
Description
patients with moderate / severe dyspnea when enrolled
Time Frame
up to 28 days
Title
Frequency of requirement for supplemental oxygen or non-invasive ventilation
Time Frame
up to 28 days
Title
Time to 2019-nCoV RT-PCR negative in upper respiratory tract specimen
Time Frame
up to 28 days
Title
Change (reduction) in 2019-nCoV viral load in upper respiratory tract specimen as assessed by area under viral load curve
Time Frame
up to 28 days
Title
Frequency of requirement for mechanical ventilation
Time Frame
up to 28 days
Title
Frequency of serious adverse events
Time Frame
up to 28 days
Title
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
Time Frame
up to 28 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jinglin Xia, MD
Phone
0577-55578166
Email
xiajinglin@fudan.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jinglin Xia, MD
Organizational Affiliation
First Affiliated Hospital of Wenzhou Medical University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Citations:
PubMed Identifier
19604271
Citation
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Results Reference
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32043983
Citation
Russell CD, Millar JE, Baillie JK. Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury. Lancet. 2020 Feb 15;395(10223):473-475. doi: 10.1016/S0140-6736(20)30317-2. Epub 2020 Feb 7. No abstract available.
Results Reference
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PubMed Identifier
32029004
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.
Results Reference
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PubMed Identifier
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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 Mar 17;323(11):1061-1069. doi: 10.1001/jama.2020.1585. Erratum In: JAMA. 2021 Mar 16;325(11):1113.
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Citation
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Citation
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Results Reference
result
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The Efficacy and Safety of Thalidomide in the Adjuvant Treatment of Moderate New Coronavirus (COVID-19) Pneumonia
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