GOREISAN for Heart Failure (GOREISAN-HF) Trial (GOREISAN-HF)

The objective of the GOREISAN-HF trial is to assess the effect of the administration of Goreisan (TJ-17) plus standard therapy compared to standard therapy alone on the improvement rate of cardiac edema and clinical outcomes in worsening congestive heart failure with volume overload.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Edema; Clinical Trial; Traditional Japanese Medicine; Kampo Medicine
• Intervention / Treatment: Drug: Goreisan; Drug: Standard Treatment

Detailed Description

Current guidelines recommend the use of loop diuretics as an indication for class I to improve HF symptoms regardless of left ventricular ejection fraction. Loop diuretics, however, are known to activate the renin-angiotensin-aldosterone system and the sympathetic nervous system, which could accelerate HF progression. Loop diuretics could also cause worsening renal function and electrolyte disturbance, and it is desirable to have an alternative drug to loop diuretics to effectively relieve congestive symptoms. Goreisan (TJ-17), a traditional Japanese medicine composed of five herbal medicines, has long been used in Japan to treat impairments of the regulation of body fluid homeostasis, including edema, and has been less likely to cause renal dysfunction and electrolyte abnormalities. We therefore planned a multicenter, randomized, interventional, parallel assignment, open-label treatment trial to evaluate the long-term effect of in-hospital initiation of Goreisan, when added to standard therapy, in patients with worsening congestive heart failure and clear signs of volume overload.

• Study Type: Interventional
• Enrollment (Anticipated): 2192
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Hidenori Yaku, MD, PhD; Phone Number: +81-75-751-4255; Email: yakuh@kuhp.kyoto-u.ac.jp

Study Locations

• Japan
  • Kyoto, Japan, 606-8507
    • Recruiting
    • Kyoto University Graduate School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Confirmed congestive heart failure (CHF) by Framingham criteria
• CHF patients with cardiac edema and signs due to cardiac edema (signs of fluid overload: lower limb edema, pulmonary effusion, or pulmonary congestion on chest x-ray)
• Elevated N-terminal pro brain-type natriuretic peptide (NT-proBNP) ≥300 pg/mL or brain natriuretic peptide (BNP) ≥100 pg/mL at enrollment
• Patients ≥ 20 years of age, male or female
• Provision of signed informed consent before any assessment is performed

Exclusion Criteria:

• Valvular repair/replacement within 12 weeks prior to enrolment or planned to undergo any of these operations after randomization
• Implantation of a cardiac resynchronization therapy (CRT) within 12 weeks prior to enrollment or intent to implant a CRT device
• Previous cardiac transplantation or implantation of a ventricular assistance device or similar device, or implantation expected after randomization
• End-stage renal failure (estimated glomerular filtration rate [eGFR] <15 mL/min/1.73m2) at enrollment
• Patients who are expected to have a life expectancy of 6 months or less
• Acute coronary syndrome at screening
• Women of child-bearing potential or women who have a positive pregnancy test at enrolment or randomization
• Treatment with herbal medicine at enrollment
• Confirmed poor tolerability of Goreisan (including cinnamon allergy)
• Considered not appropriate for the participation of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Goreisan; Goreisan (TJ-17) will be added at a dose of 7.5g per day to standard treatment	Drug: Goreisan; Add Goreisan 7.5g per day to standard treatment with the intention to reduce or discontinue the existing diuretics
Active Comparator: No Goreisan; Standard treatment without Goreisan (TJ-17)	Drug: Standard Treatment; Standard therapy without Goreisan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of cardiac edema	Cardiac edema is defined as conditions having one or more following conditions: lower limb edema, pleural effusion, or pulmonary congestion on chest x-ray. Lower limb edema, pleural effusion, and pulmonary congestion are assessed by investigators. Improvement is defined as the disappearance of all signs of cardiac edema.	1 year
Composite endpoint of all-cause death or hospitalization	Composite of death from any cause or hospitalization from any cause.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score	The KCCQ is a validated self-administered instrument of quality of life and health status in heart failure (HF) patients. The clinical summary score is a composite assessment of physical limitation, total symptom score, health-related quality of life, and social limitation scores. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.	6 months
Change in loop diuretics dose	Loop diuretic dose will be calculated as furosemide-equivalent dose.	6 months
Change in loop diuretics dose	Loop diuretic dose will be calculated as furosemide-equivalent dose.	1 year
Composite endpoint of sustained decline in eGFR ≥50%, ESRD (end stage renal disease) or renal death	End Stage Renal Disease (ESRD) is defined as: Sustained eGFR <15 mL/min/1.73m2, Chronic dialysis treatment or, receiving a renal transplant. Renal death is defined as renal failure as the underlying cause of death.	3 years
Adverse drug event	Adverse drug event is an injury resulting from medical intervention related to any drug.	3 years
Change in a composite congestion score	Dyspnea, fatigue, orthopnea, jugular vein distention, rales, plueral effusion, and lower limb edema are assessed on a standardized 4-point scale ranging from 0 to 3. A composite congestion score is calculated by summing the individual scores for dyspnea, fatigue, orthopnea, jugular vein distention, rales, plueral effusion, and lower limb edema.	1 month
Change in a composite congestion score	Dyspnea, fatigue, orthopnea, jugular vein distention, rales, plueral effusion, and lower limb edema are assessed on a standardized 4-point scale ranging from 0 to 3. A composite congestion score is calculated by summing the individual scores for dyspnea, fatigue, orthopnea, jugular vein distention, rales, plueral effusion, and lower limb edema.	6 months
Change in a composite congestion score	Dyspnea, fatigue, orthopnea, jugular vein distention, rales, plueral effusion, and lower limb edema are assessed on a standardized 4-point scale ranging from 0 to 3. A composite congestion score is calculated by summing the individual scores for dyspnea, fatigue, orthopnea, jugular vein distention, rales, plueral effusion, and lower limb edema.	1 year
All-cause hospitalization	Hospitalization from any cause.	3 years
Composite endpoint of all-cause death or hospitalization for heart failure	Composite of death from any cause or hospitalization for heart failure.	3 years
Hospitalization for heart failure	Hospitalization for heart failure.	3 years
All-cause death	Death from any cause.	3 years
Non-cardiovascular death	Death other than death from cardiac or vascular diseases.	3 years
Change in New York Heart Association (NYHA) functional class	Change in New York Heart Association (NYHA) functional class, a well established grading scale to classify a patients' level of functionality based on the signs and symptoms of patient with heart failure.	6 months
Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP)	Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP).	1 month
Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP)	Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP).	6 month
Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP)	Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP).	1 year
Direct healthcare cost	Direct healthcare cost (Japanese Yen) from the time of randomization to 12 months was obained from the claim data patients.	1 year

Collaborators and Investigators

• Sponsor: Takeshi Morimoto
• Investigators: Study Chair: Takeshi Kimura, MD, PhD, Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2021
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): March 1, 2026

Study Registration Dates

• First Submitted: December 20, 2020
• First Submitted That Met QC Criteria: December 30, 2020
• First Posted (Actual): December 31, 2020

Study Record Updates

• Last Update Posted (Actual): April 3, 2023
• Last Update Submitted That Met QC Criteria: March 31, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Heart Failure; Edema; Clinical Trial; Traditional Japanese Medicine; Goreisan (TJ-17)
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: Y0075; jRCT (Registry Identifier: jRCT2071220069)

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