GOREISAN for Heart Failure (GOREISAN-HF) Trial

Sponsor

Takeshi Morimoto (Other)

Overall Status

Recruiting

CT.gov ID

NCT04691700

Collaborator

(none)

2,192

Enrollment

Location

Arms

61.3

Anticipated Duration (Months)

35.7

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure Edema Traditional Japanese Medicine Kampo Medicine Clinical Trial	Drug: Goreisan Drug: Standard Treatment	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

2192 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

GOREISAN for Heart Failure (GOREISAN-HF) Trial

Actual Study Start Date :

Jan 19, 2021

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Mar 1, 2026

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Improvement of cardiac edema [1 year]
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 [3 years]
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 [6 months]
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 [6 months]
Loop diuretic dose will be calculated as furosemide-equivalent dose.
Change in loop diuretics dose [1 year]
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 [3 years]
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 [3 years]
Adverse drug event is an injury resulting from medical intervention related to any drug.
Change in a composite congestion score [1 month]
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 [6 months]
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 [1 year]
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 [3 years]
Hospitalization from any cause.
Composite endpoint of all-cause death or hospitalization for heart failure [3 years]
Composite of death from any cause or hospitalization for heart failure.
Hospitalization for heart failure [3 years]
Hospitalization for heart failure.
All-cause death [3 years]
Death from any cause.
Non-cardiovascular death [3 years]
Death other than death from cardiac or vascular diseases.
Change in New York Heart Association (NYHA) functional class [6 months]
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) [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]
Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP).
Direct healthcare cost [1 year]
Direct healthcare cost (Japanese Yen) from the time of randomization to 12 months was obained from the claim data patients.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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