Back to resultsGOREISAN for Heart Failure (GOREISAN-HF) Trial (GOREISAN-HF)
Primary Purpose
Heart Failure, Edema, Traditional Japanese Medicine
Status
Recruiting
Phase
Phase 4
Locations
Japan
Study Type
Interventional
Intervention
Goreisan
Standard Treatment
Sponsored by
About this trial
This is an interventional treatment trial for Heart Failure focused on measuring Heart Failure, Edema, Traditional Japanese Medicine, Goreisan (TJ-17), Clinical Trial
Eligibility Criteria
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
Sites / Locations
- Kyoto University Graduate School of MedicineRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Goreisan
No Goreisan
Arm Description
Goreisan (TJ-17) will be added at a dose of 7.5g per day to standard treatment
Standard treatment without Goreisan (TJ-17)
Outcomes
Primary Outcome Measures
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.
Composite endpoint of all-cause death or hospitalization
Composite of death from any cause or hospitalization from any cause.
Secondary Outcome Measures
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.
Change in loop diuretics dose
Loop diuretic dose will be calculated as furosemide-equivalent dose.
Change in loop diuretics dose
Loop diuretic dose will be calculated as furosemide-equivalent dose.
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.
Adverse drug event
Adverse drug event is an injury resulting from medical intervention related to any drug.
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.
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.
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.
All-cause hospitalization
Hospitalization from any cause.
Composite endpoint of all-cause death or hospitalization for heart failure
Composite of death from any cause or hospitalization for heart failure.
Hospitalization for heart failure
Hospitalization for heart failure.
All-cause death
Death from any cause.
Non-cardiovascular death
Death other than death from cardiac or vascular diseases.
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.
Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP)
Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP).
Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP)
Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP).
Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP)
Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP).
Direct healthcare cost
Direct healthcare cost (Japanese Yen) from the time of randomization to 12 months was obained from the claim data patients.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04691700
Brief Title
GOREISAN for Heart Failure (GOREISAN-HF) Trial
Acronym
GOREISAN-HF
Official Title
GOREISAN for Heart Failure (GOREISAN-HF) Trial
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 19, 2021 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
March 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Takeshi Morimoto
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure, Edema, Traditional Japanese Medicine, Kampo Medicine, Clinical Trial
Keywords
Heart Failure, Edema, Traditional Japanese Medicine, Goreisan (TJ-17), Clinical Trial
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
2192 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Goreisan
Arm Type
Active Comparator
Arm Description
Goreisan (TJ-17) will be added at a dose of 7.5g per day to standard treatment
Arm Title
No Goreisan
Arm Type
Active Comparator
Arm Description
Standard treatment without Goreisan (TJ-17)
Intervention Type
Drug
Intervention Name(s)
Goreisan
Intervention Description
Add Goreisan 7.5g per day to standard treatment with the intention to reduce or discontinue the existing diuretics
Intervention Type
Drug
Intervention Name(s)
Standard Treatment
Intervention Description
Standard therapy without Goreisan
Primary Outcome Measure Information:
Title
Improvement of cardiac edema
Description
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.
Time Frame
1 year
Title
Composite endpoint of all-cause death or hospitalization
Description
Composite of death from any cause or hospitalization from any cause.
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score
Description
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.
Time Frame
6 months
Title
Change in loop diuretics dose
Description
Loop diuretic dose will be calculated as furosemide-equivalent dose.
Time Frame
6 months
Title
Change in loop diuretics dose
Description
Loop diuretic dose will be calculated as furosemide-equivalent dose.
Time Frame
1 year
Title
Composite endpoint of sustained decline in eGFR ≥50%, ESRD (end stage renal disease) or renal death
Description
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.
Time Frame
3 years
Title
Adverse drug event
Description
Adverse drug event is an injury resulting from medical intervention related to any drug.
Time Frame
3 years
Title
Change in a composite congestion score
Description
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.
Time Frame
1 month
Title
Change in a composite congestion score
Description
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.
Time Frame
6 months
Title
Change in a composite congestion score
Description
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.
Time Frame
1 year
Title
All-cause hospitalization
Description
Hospitalization from any cause.
Time Frame
3 years
Title
Composite endpoint of all-cause death or hospitalization for heart failure
Description
Composite of death from any cause or hospitalization for heart failure.
Time Frame
3 years
Title
Hospitalization for heart failure
Description
Hospitalization for heart failure.
Time Frame
3 years
Title
All-cause death
Description
Death from any cause.
Time Frame
3 years
Title
Non-cardiovascular death
Description
Death other than death from cardiac or vascular diseases.
Time Frame
3 years
Title
Change in New York Heart Association (NYHA) functional class
Description
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.
Time Frame
6 months
Title
Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP)
Description
Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP).
Time Frame
1 month
Title
Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP)
Description
Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP).
Time Frame
6 month
Title
Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP)
Description
Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP).
Time Frame
1 year
Title
Direct healthcare cost
Description
Direct healthcare cost (Japanese Yen) from the time of randomization to 12 months was obained from the claim data patients.
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Takeshi Kimura, MD, PhD
Phone
+81-75-751-4254
Email
taketaka@kuhp.kyoto-u.ac.jp
First Name & Middle Initial & Last Name or Official Title & Degree
Hidenori Yaku, MD, PhD
Phone
+81-75-751-4255
Email
yakuh@kuhp.kyoto-u.ac.jp
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Takeshi Kimura, MD, PhD
Organizational Affiliation
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine
Official's Role
Study Chair
Facility Information:
Facility Name
Kyoto University Graduate School of Medicine
City
Kyoto
ZIP/Postal Code
606-8507
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Takeshi Kimura, MD, PhD
Phone
+81-75-751-4254
Email
taketaka@kuhp.kyoto-u.ac.jp
First Name & Middle Initial & Last Name & Degree
Takeshi Kimura, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
GOREISAN for Heart Failure (GOREISAN-HF) Trial
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