GOREISAN for Heart Failure (GOREISAN-HF) Trial

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Heart Failure, Edema, Traditional Japanese Medicine, Kampo Medicine, Clinical Trial

Intervention / Treatment
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* Drug: Goreisan
* Drug: Standard Treatment


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Edema, Traditional Japanese Medicine, Goreisan (TJ-17), Clinical Trial