Silymarin in COVID-19 Patients Admitted to Hospital With Elevated Liver Enzymes

Study Overview
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Brief Summary
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Of patients admitted to an internal medicine ward with internistic diagnosis/es together with COVID-19, substantial proportion has elevated liver enzymes. silymarin / silibinin (milk thistle extract) has been approved as an add-on therapy in various acute and chronic liver diseases; moreover, there is evidence to suggest that it's dual effect (anti-viral and immune-modulatory) might be of benefit in patients infected with SARS-CoV-2. As there is no effective/approved pharmacotherapy for COVID-19, a pilot study with Silymarine in hospitalised patients has been undertaken

Detailed Description
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According to the Bosch-Barrera et al. paper of 2021, silibinin in a daily dose of more than 1000 mg could improve clinical course of COVID-19 by its dual action: 1.direct inhibition of SARS-CoV-2 replication as well as 2.modulation of innate immune response - 2a. its initial (hyper)inflammation as well as 2b. later reparative phase, respectively. Moreover, the drug is known for its safety and has been approved and widely used in the region for liver diseases. Therefore, the investigation was set out to determine the efficacy of silymarin (compound closely related to Silibinin which is available in the region) in improving the outcome of a liver disease and of COVID-19, respectively.

Official Title
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Does Silymarin Mitigate Clinical Course of COVID-19 in Patients Admitted to an Internal Medicine Ward With Elevated Liver Enzymes?

Conditions
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Covid19, Liver Diseases

Intervention / Treatment
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* Drug: Silymarin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: consecutive, adult, admitted to an internal medicine ward with internistic diagnosis, together with COVID-19, and elevated liver enzymes (any of AST, ALT, GGT, ALP), provided written informed consent Exclusion Criteria: too sick - terminal illness (no potential for recovery); critical condition on admission requiring immediate tracheal intubation; or any extra-pulmonary organ failure; completely vaccinated against COVID19.

Ages Eligible for Study
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Minimum Age: 19 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: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Prospective open label study using historical cohort for propensity-match analysis
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: LAGOSA ARM<br>Consecutively admitted patients will be allocated silymarin tablets (150 mg each) T.I.D. 3-2-2 | Drug: Silymarin<br>* Silymarine tablets will be provided irrespective of meal by a registered nurse T.I.D<br>* Other names: LAGOSA;|
| No Intervention: Control arm<br>Consecutive patients with the same inclusion/exclusion criteria as in active arm, hospitalised at the same department before the initiation of the study (historical controls) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in the COVID-19 stage of at least 1 point | Evolution of COVID-19 will be recorded according to a WHO criteria and reported as worsening (including death) / no change / improvement | During the hospital stay - up to around 21 days | 
| Improvement in the activity of aminotranspherases | Change in the level of ALT | During the hospital stay - up to around 21 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improvement in the diabetes control | Change in the glycemia | During the hospital stay - up to around 21 days | 
| Improvement in the blood inflammatory markers | Change in C-reactive protein levels | During the hospital stay - up to around 21 days | 
| Improvement in the dyspnea | Improvement of at least one point in the NYHA classification | During the hospital stay - up to around 21 days | 
| Improvement in the acute kidney injury | Any improvement in the serum creatinine level | During the hospital stay - up to around 21 days | 
| Improvement in the blood inflammatory markers | Improvement in the interleukin - 6 level | During the hospital stay - up to around 21 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, In-hospital mortality, Internal medicine