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GOREISAN for Heart Failure (GOREISAN-HF) Trial

Phase 4
Recruiting
Conditions
Heart Failure
Edema
Traditional Japanese Medicine
Kampo Medicine
Clinical Trial
Interventions
Drug: Goreisan
Drug: Standard Treatment
Registration Number
NCT04691700
Lead Sponsor
Takeshi Morimoto
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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
1164
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
GoreisanGoreisanGoreisan (TJ-17) will be added at a dose of 7.5g per day to standard treatment
No GoreisanStandard TreatmentStandard treatment without Goreisan (TJ-17)
Primary Outcome Measures
NameTimeMethod
Composite endpoint of all-cause death or hospitalization3 years

Composite of death from any cause or hospitalization from any cause.

Improvement of cardiac edema1 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.

Secondary Outcome Measures
NameTimeMethod
Change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score6 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.

Composite endpoint of sustained decline in eGFR ≥50%, ESRD (end stage renal disease) or renal death3 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 event3 years

Adverse drug event is an injury resulting from medical intervention related to any drug.

Change in loop diuretics dose1 year

Loop diuretic dose will be calculated as furosemide-equivalent dose.

Change in a composite congestion score1 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 hospitalization3 years

Hospitalization from any cause.

Composite endpoint of all-cause death or hospitalization for heart failure3 years

Composite of death from any cause or hospitalization for heart failure.

Hospitalization for heart failure3 years

Hospitalization for heart failure.

All-cause death3 years

Death from any cause.

Non-cardiovascular death3 years

Death other than death from cardiac or vascular diseases.

Change in New York Heart Association (NYHA) functional class6 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 year

Change in N-terminal pro brain-type natriuretic peptide (NT-proBNP).

Direct healthcare cost1 year

Direct healthcare cost (Japanese Yen) from the time of randomization to 12 months was obained from the claim data patients.

Trial Locations

Locations (1)

Kyoto University Graduate School of Medicine

🇯🇵

Kyoto, Japan

Kyoto University Graduate School of Medicine
🇯🇵Kyoto, Japan
Takeshi Kimura, MD, PhD
Contact

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