A Multicenter Observational Study on Safety of the Herbal Medicines at Inpatient Setting

Study Overview
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Brief Summary
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Prospective observations on safety of the herbal medicines regarding liver and kidney injuries at inpatient setting of four sites in South Korea which are located at each quadrant of the country. In a previous study (PMID 28634823), six women presented liver injuries by herbs and similar findings were also reported. That knowledge has been developed to design the observations of females (19-80 ages) at least 2 weeks' hospitalization with weekly routine lab tests to obtain the occurrence of liver or kidney injuries and the profiles on micro biomarkers throughout the hospitalization period, and then, the follow-up test will be conducted in outpatient setting.

Detailed Description
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Total 500 inpatients will be observed to assess safety of herbal medicines with the balance of 60 to 110 each site. After obtaining the informed consent from patient, blood draw and urine collection are conducted prior to intake of the herbal medicine, blood draw and urine collection are routinely done every week throughout the whole admission period. The primary outcomes are, 1) liver for alanine aminotransferase (ALT), RUCAM (in case of causality assessment when ALT≥3 upper normal limit) and new biomarker, mircoRNA-122 and 2) kidney for urine creatinine, blood urea nitrogen (BUN) and new biomarker, Neutrophil gelatinase-associated lipocalin (NGAL). The secondary outcomes are, 1) liver for aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyltransferase (γ-GT), total bilirubin and new biomarker, glutamate dehydrogenase (GLDH) and 2) kidney for serum creatinine and new biomarker, kidney injury molecule-1 (KIM-1). The follow-up will be done by the study doctors based on their decision on the inpatient after discharge.

Official Title
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Safety Assessment of the Frequently Used Herbal Medicines at Inpatient Setting: a Multicenter, Prospective Observational Study

Conditions
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Drug Induced Liver Injury, Drug-Induced Kidney Injury, Herbal Medicine Adverse Reaction

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female whose age is between 19 and 80 Inpatient expected to stay at least 2 weeks and to intake herbal medicine Who signed voluntarily informed consent. Exclusion Criteria: Who were short of stay for 2 weeks or stopped intaking herbal medicine Who had problems physically or mentally by investigator

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Inpatient participant<br>Inpatients who signed the informed consent form that she will be observed during the hospitalization period | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alanine aminotransferase (ALT) (U/L), if ALT >3 upper normal limit, Roussel uclaf casuality assessment method scoring | Routine check-up test item and causality assessment on liver functions | Activity change from Admission (0 week; ALT) up to discharge (12 weeks; ALT) | 
| Blood urea nitrogen (BUN) (mg/dL) | Routine check-up test item on kidney functions | Activity change from Admission (0 week; BUN) up to discharge (12 weeks; BUN) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver function tests: AST (U/L), ALP (U/L), γ-GT (U/L), total bilirubin (mg/dL). Drug induced-liver injury biomarkers: microRNA-122 (miR122), Glutamate dehydrogenase (GLDH) | Routine check-up test items and newly developed biomarkers on liver functions | Time-dependent Profiles from Admission (0 week), 1 week, 2 weeks, 3 weeks up to discharge (12 weeks) | 
| Kidney function tests: Urine creatinine (mg/dL), Serum creatinine (mg/dL). Drug induced-kidney injury biomarkers: Neutrophil gelatinase-associated lipocalin, Kidney Injury Molecule-1 | Routine check-up test items and newly developed biomarkers on kidney functions | Time-dependent Profiles from Admission (0 week), 1 week, 2 weeks, 3 weeks up to discharge (12 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Herbal Medicine, Drug Induced Liver Injury, Drug-Induced Kidney Injury, Prospective Observation, Multicenter Study, Safety