Clinical trial NCT04269486: A Multicenter Observational Study on Safety of the Herbal Medicines at Inpatient Setting
Official title: Safety Assessment of the Frequently Used Herbal Medicines at Inpatient Setting: a Multicenter, Prospective Observational Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Drug Induced Liver Injury
Drug-Induced Kidney Injury
Herbal Medicine Adverse Reaction
Keywords: Safety
Herbal Medicine
Drug Induced Liver Injury
Drug-Induced Kidney Injury
Prospective Observation
Multicenter Study
Lead sponsor: Korea Institute of Oriental Medicine
Sponsor class: OTHER_GOV
Collaborators: name: Semyung University
name: Dongshin Seoul Korean Medicine Hospital
name: CHUNG YEON Korean Medicine Hospital
name: Korean Medicine Hospital of Pusan National University
name: DongGuk University
First posted: 2020-02-13
Enrollment: 287
Sex: FEMALE
Minimum age (years): 19
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Alanine aminotransferase (ALT) (U/L), if ALT >3 upper normal limit, Roussel uclaf casuality assessment method scoring
timeFrame: Activity change from Admission (0 week; ALT) up to discharge (12 weeks; ALT)
measure: Blood urea nitrogen (BUN) (mg/dL)
timeFrame: Activity change from Admission (0 week; BUN) up to discharge (12 weeks; BUN)
Secondary outcomes:
measure: 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)
timeFrame: Time-dependent Profiles from Admission (0 week), 1 week, 2 weeks, 3 weeks up to discharge (12 weeks)
measure: Kidney function tests: Urine creatinine (mg/dL), Serum creatinine (mg/dL). Drug induced-kidney injury biomarkers: Neutrophil gelatinase-associated lipocalin, Kidney Injury Molecule-1
timeFrame: Time-dependent Profiles from Admission (0 week), 1 week, 2 weeks, 3 weeks up to discharge (12 weeks)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Five tertiary Korean Medicine Hospital (Jecheon, Yangsan, Gwangju, Seoul, Bundang)
Study officials:
affiliation: Korea Institute of Oriental Medicine
name: Dal-Seok Oh, OMD, PhD
role: PRINCIPAL_INVESTIGATOR
References: