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.

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.

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