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

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

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.

Study Overview

• Status: Terminated
• Conditions: Drug Induced Liver Injury; Drug-Induced Kidney Injury; Herbal Medicine Adverse Reaction

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 287

Contacts and Locations

Study Locations

• South Korea
  • Seoul, South Korea
    • Five tertiary Korean Medicine Hospital (Jecheon, Yangsan, Gwangju, Seoul, Bundang)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The female inpatients who showed their autonomy and voluntarily signed informed consent on the observations thorughout hospitalization period.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Inpatient participant; Inpatients who signed the informed consent form that she will be observed during the hospitalization period

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Korea Institute of Oriental Medicine
• Collaborators: DongGuk University; Korean Medicine Hospital of Pusan National University; Semyung University; Dongshin Seoul Korean Medicine Hospital; CHUNG YEON Korean Medicine Hospital
• Investigators: Principal Investigator: Dal-Seok Oh, OMD, PhD, Korea Institute of Oriental Medicine

Publications and helpful links

Helpful Links

• Online source on the previous study paper

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2019
• Primary Completion (Actual): March 30, 2024
• Study Completion (Actual): December 31, 2024

Study Registration Dates

• First Submitted: November 26, 2019
• First Submitted That Met QC Criteria: February 12, 2020
• First Posted (Actual): February 13, 2020

Study Record Updates

• Last Update Posted (Estimated): September 3, 2025
• Last Update Submitted That Met QC Criteria: August 26, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Safety; Herbal Medicine; Multicenter Study; Drug Induced Liver Injury; Drug-Induced Kidney Injury; Prospective Observation
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Chemically-Induced Disorders; Drug-Related Side Effects and Adverse Reactions; Poisoning; Chemical and Drug Induced Liver Injury
• Other Study ID Numbers: KIOS1901

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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