Clinical trial NCT04691700: GOREISAN for Heart Failure (GOREISAN-HF) Trial
Official title: GOREISAN for Heart Failure (GOREISAN-HF) Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Heart Failure
Edema
Traditional Japanese Medicine
Kampo Medicine
Clinical Trial
Keywords: Heart Failure
Edema
Traditional Japanese Medicine
Goreisan (TJ-17)
Clinical Trial
Lead sponsor: Kyoto University, Graduate School of Medicine
Sponsor class: OTHER
First posted: 2020-12-31
Enrollment: 1164
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Improvement of cardiac edema
timeFrame: 1 year
measure: Composite endpoint of all-cause death or hospitalization
timeFrame: 3 years
Secondary outcomes:
measure: Change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score
timeFrame: 6 months
measure: Change in loop diuretics dose
timeFrame: 6 months
measure: Change in loop diuretics dose
timeFrame: 1 year
measure: Composite endpoint of sustained decline in eGFR ≥50%, ESRD (end stage renal disease) or renal death
timeFrame: 3 years
measure: Adverse drug event
timeFrame: 3 years
measure: Change in a composite congestion score
timeFrame: 1 month
measure: Change in a composite congestion score
timeFrame: 6 months
measure: Change in a composite congestion score
timeFrame: 1 year
measure: All-cause hospitalization
timeFrame: 3 years
measure: Composite endpoint of all-cause death or hospitalization for heart failure
timeFrame: 3 years
measure: Hospitalization for heart failure
timeFrame: 3 years
measure: All-cause death
timeFrame: 3 years
measure: Non-cardiovascular death
timeFrame: 3 years
measure: Change in New York Heart Association (NYHA) functional class
timeFrame: 6 months
measure: Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP)
timeFrame: 1 month
measure: Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP)
timeFrame: 6 month
measure: Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP)
timeFrame: 1 year
measure: Direct healthcare cost
timeFrame: 1 year
Other outcomes:
Locations:
city: Kyoto
country: Japan
facility: Kyoto University Graduate School of Medicine
Study officials:
affiliation: Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine
name: Takeshi Kimura, MD, PhD
role: STUDY_CHAIR
References: