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The coronavirus (SARS-CoV-2) is a new strain of coronavirus found in human in 2019, which causes epidemic worldwide. A study found that the increase in hyaluronic acid levels is closely related to the clinical symptoms of COVID-19, including pulmonary ground glass lesions, lymphocytopenia, immune response and cytokine storms, systemic vascular diseases, thrombotic coagulation disorders, which suggests that hyaluronic acid could be an important target for COVID-19 treatment and could improve the clinical symptoms of COVID-19 patients.
The results from a recent clinical trial recruited 144 patients with COVID-19 show that the inhibitor of hyaluronic acid synthesis, hymecromone, can significantly improve clinical symptoms, such as lung lesions and lymphocytopenia in COVID-19 patients. Therefore, hymecromone has the potential to become one of the options of COVID-19 treatment.
This study is a single-center, randomized, parallel controlled, double-blind clinical trial designed to evaluate the efficacy and safety of Hymecromone tablets in subjects aged 18-90 years (with boundary values) with a confirmed mild or moderate form of COVID-19 infection. The aim of this study is to optimize the program of the combination of hymecromone in the treatment of COVID-19 to improve the therapeutic effect.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental group | Experimental | Conventional treatment combined with Hymecromone tablets, 0.4g , tid ac, 7 days. |
|
| Control group | Placebo Comparator | Conventional treatment combined with placebo. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Hymecromone tablets | Drug | Conventional treatment combined with Hymecromone tablets, 0.4g , tid ac, 7 days. |
|
| Measure | Description | Time Frame |
|---|---|---|
| The proportion of subjects who developed disease progression. | To compare the proportion of subjects in the experimental group and the control group who developed disease progression within 28 days after initial treatment. | Within 28 days after initial treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| The incidence of adverse events and serious adverse events. | To compare the incidence of adverse events and serious adverse events related to the study treatment in the experimental group and the control group. | The whole test process. |
| The time gap of COVID-19 virus clearance. |
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Inclusion Criteria:
Exclusion Criteria:
Participants who have any of the following conditions when screening:
Participants who have suspected/active infections during the screening period including uncontrolled active bacterial, viral or fungal infections that require systemic treatment, except COVID-19 virus infections;
Participants who have any active autoimmune diseases during the screening period and need to be treated with immunosuppressants, including biological agents;
Participants who have a medical history of organ transplantation, or plan for organ transplantation including liver transplantation;
Participants who need a loading dose of anti-platelet drugs, such as aspirin (>300 mg/day) and clopidogrel (>300 mg/day);
Participants who have a medical history of central nervous system and digestive system bleeding, or a tendency of gastrointestinal bleeding, local active ulcer lesions included, in the last three months;
Participants who have biliary obstruction;
Female participants who are pregnant or breast-feeding or plan to be pregnant within this study period;
Male participants whose wife or partner plan to be pregnant within this study period.
Participants who have taken the drugs containing coumarin compounds, such as warfarin, within 3 days before screening;
Participants who have other diseases requiring hospitalization and/or in a need of surgical treatment within 7 days before screening, or have suffered from life-threatening diseases within 30 days before screening;
Participants who have known allergies to any of the components used in the formulation of the interventions;
Participants who have taken a part in a clinical study of an investigational intervention in the last 28 days. After 5 half-lives or 28 days, whichever is longer, can be allowed for screening;
Participants who are not suitable for this trial, and with any medical condition will compromise their own safety.
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Hao Fang | Contact | +86 21-64041990 | fang.hao@zs-hospital.sh.cn |
| Name | Affiliation | Role |
|---|---|---|
| Hao Fang | Zhong Shan Hospital affiliated to Fudan University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Zhong Shan Hospital affiliated to Fudan University | Recruiting | Shanghai | Shanghai Municipality | 200030 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35304437 | Background | Yang S, Ling Y, Zhao F, Li W, Song Z, Wang L, Li Q, Liu M, Tong Y, Chen L, Ru D, Zhang T, Zhou K, Zhang B, Xu P, Yang Z, Li W, Song Y, Xu J, Zhu T, Shan F, Yu W, Lu H. Hymecromone: a clinical prescription hyaluronan inhibitor for efficiently blocking COVID-19 progression. Signal Transduct Target Ther. 2022 Mar 18;7(1):91. doi: 10.1038/s41392-022-00952-w. | |
| 35124429 |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D006923 | Hymecromone |
| ID | Term |
|---|---|
| D014468 | Umbelliferones |
| D003374 | Coumarins |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 |
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| Placebo | Other | Conventional treatment combined with Placebo. |
|
To compare the time of virus clearance by COVID-19 virus tests in the experimental group and the control group. |
| From the beginning of the research to the negative report of COVID-19 nucleic acid. |
| The clinical recovery time of the COVID-19 virus infection-related symptoms. | To compare the clinical recovery time of the COVID-19 virus infection-related symptoms in the experimental group with the control group. | From the beginning of the research to the disappearance of clinical symptoms. |
| The change of the serum hyaluronic acid. | To compare the serum hyaluronic acid level between baseline and the end of study observation of all subjects in the experimental group and the control group. | Between baseline and the end of study observation. |
| Li W, Yang S, Xu P, Zhang D, Tong Y, Chen L, Jia B, Li A, Lian C, Ru D, Zhang B, Liu M, Chen C, Fu W, Yuan S, Gu C, Wang L, Li W, Liang Y, Yang Z, Ren X, Wang S, Zhang X, Song Y, Xie Y, Lu H, Xu J, Wang H, Yu W. SARS-CoV-2 RNA elements share human sequence identity and upregulate hyaluronan via NamiRNA-enhancer network. EBioMedicine. 2022 Feb;76:103861. doi: 10.1016/j.ebiom.2022.103861. Epub 2022 Feb 3. |
| 25852691 | Background | Nagy N, Kuipers HF, Frymoyer AR, Ishak HD, Bollyky JB, Wight TN, Bollyky PL. 4-methylumbelliferone treatment and hyaluronan inhibition as a therapeutic strategy in inflammation, autoimmunity, and cancer. Front Immunol. 2015 Mar 23;6:123. doi: 10.3389/fimmu.2015.00123. eCollection 2015. |
| 37055910 | Derived | Salman L, Martinez L, Faddoul G, Manning C, Ali K, Salman M, Vazquez-Padron R. Hyaluronan Inhibition as a Therapeutic Target for Diabetic Kidney Disease: What Is Next? Kidney360. 2023 Jun 1;4(6):e851-e860. doi: 10.34067/KID.0000000000000126. Epub 2023 Apr 14. |
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |