SHengXIaN-QuYu DEcoction in the Treatment of Heart Failure With Reduced Ejection Fraction

Heart Failure With Reduced Ejection Fraction Clinical Trial

— SHINE-HF  

Official title:

Effects of "ShengXian-QuYu Decoction" on Quality of Life, Symptoms, and Biomarkers in Heart Failure Patients With Reduced Ejection Fraction: a Nationwide, Multicenter, Parallel Group, Randomized, Double-Blind, Placebo-Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05583773
• Other study ID #: 2022-NHLHCRF-LX-02-0102
• Status: Recruiting
• Phase: Phase 4
• Start date: March 29, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: February 2024
• Source: China-Japan Friendship Hospital
• Contact: Mengxi Yang, Dr.
• Phone: +8615120049452
• Email: mxtezuka[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to conduct a multicenter, randomized clinical trial to evaluate the effect of "ShengXian-QuYu Decoction" on quality of life , symptoms, and biomarkers in heart failure patients with reduced ejection fraction.

Description:

This is a nationwide, multicenter, parallel group, randomized, double-blind, placebo-controlled study in patients with heart failure with reduced ejection fraction (HFrEF), evaluating the effect of "ShengXian-QuYu Decoction" versus placebo, given twice daily in addition to background regional standard of care. The effect of "ShengXian-QuYu Decoction"on quality of life, symptoms and biomarkers will be evaluated.

The primary and secondary endpoints will be examined in subgroups determined by baseline variables reflecting demography, heart failure characteristics, Traditional Chinese Medicine syndrome type, diabetes status, kidney function, left ventricular ejection fraction, natriuretic peptide, and additional co-morbidities, concomitant medications, and others.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 564
• Est. completion date: December 31, 2025
• Est. primary completion date: April 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female, aged =18 years at the time of consent.

2. Established documented diagnosis of symptomatic HFrEF (NYHA functional class II-IV).

3. LVEF=50%.

4. NT-proBNP >600 pg/ml or BNP =150 pg/ml (or if hospitalized for heart failure within the previous 12 months, NT-proBNP =400 pg/ml or BNP =100 pg/ml) at enrolment.

5. Provision of signed informed consent prior to any study specific procedures.

Exclusion Criteria:

1. Current acute decompensated HF or hospitalization due to decompensated HF, ACS, stroke or transient ischemic attack (TIA), coronary revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass grafting [CABG]) or valvular repair/replacement, or other major cardiovascular surgery within 4 weeks prior to enrolment.

2. Uncontrolled severe arrhythmia.

3. Planned to undergo heart transplantation or device implantation.

4. Hepatic impairment aspartate transaminase [AST] or alanine transaminase [ALT] >3x the upper limit of normal [ULN]; or total bilirubin >2x ULN at time of enrolment).

5. Severe infection.

6. eGFR <30 mL/min/1.73 m^2 by CKD-EPI.

7. Active malignancy requiring treatment at the time of visit 1.

8. Women of child-bearing potential who are not willing to use a medically accepted method of contraception that is considered reliable in the judgment of the investigator OR women who have a positive pregnancy test at enrolment or randomization OR women who are breast-feeding.

9. Any condition outside the CV and renal disease area, such as but not limited to malignancy, with a life expectancy of less than 1 years based on investigator's clinical judgement.

10. Systolic blood pressure < 90 mmHg, or systolic blood pressure = 180 mmHg, or diastolic blood pressure = 110 mmHg on 2 consecutive measurements.

11. Heart failure due to infiltrative cardiomyopathies(cardiac amyloidosis, etc.), fulminant myocarditis, constrictive pericarditis.

12. Participation in another clinical study.

13. Inability of the patient, in the opinion of the investigator, to understand and/or comply with study medications, procedures and/or follow-up OR any conditions that, in the opinion of the investigator, may render the patient unable to complete the study.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Reduced Ejection Fraction

Intervention

Drug:
• ShengXian-QuYu Decoction
Specification: 30ml/bag, given twice daily, per oral use.

Other:
• Placebo
Placebo matching ShengXian-QuYu Decoction, 30ml/bag, given twice daily, per oral use.

Locations

Country	Name	City	State
China	Tangxian County Traditional Chinese Medicine Hospital	Baoding	Hebei
China	Beijing Fengtai Hospital of Integrated Traditional Chinese and Western Medicine	Beijing	Beijing
China	Changping District Traditional Chinese Medicine Hospital	Beijing	Beijing
China	China-Japan Friendship Hospital	Beijing	Beijing
China	Dongfang Hospital Affiliated to Beijing University of Chinese Medicine	Beijing	Beijing
China	Huairou District Traditional Chinese Medicine Hospital of Beijing	Beijing	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	Heji Hospital Affiliated to Changzhi Medical College	Changzhi	Shanxi
China	Shanxi Changzhi Hospital of Traditional Chinese Medicine	Changzhi	Shanxi
China	The Affiliated Hospital of Changzhi Institute of Traditional Chinese Medicine	Changzhi	Shanxi
China	Gongyi City People's Hospital	Gongyi	Henan
China	Jining Hospital of Traditional Chinese Medicine	Jining	Shandong
China	Linhai Hospital of Traditional Chinese Medicine	Linhai	Zhejiang
China	The Affiliated Hospital of Qingdao University	Qingdao	Shandong
China	Funing Hospital of Traditional Chinese Medicine	Qinhuangdao	Hebei
China	Jixian Chinese Traditional Hospital	Tianjin	Tianjin
China	Yangzhou Tranditional Chinese Medicine Hospital	Yangzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
China-Japan Friendship Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Subjects Included in the Composite Endpoint of Cardiovascular Death and Worsening Heart Failure	The composite CV endpoint is defined as cardiovascular death, hospitalization due to heart failure or urgent visit required intravenous treatment due to heart failure.	Up to 12 weeks
Other	Subjects Included in the Composite Endpoint of Cardiovascular Death and Worsening Heart Failure	The composite CV endpoint is defined as cardiovascular death, hospitalization due to heart failure or urgent visit required intravenous treatment due to heart failure.	Up to 26 weeks
Other	Renal Composite Endpoint	The renal composite endpoint included composite of doubling of serum creatinine (DoSC), end-stage kidney disease (ESKD), and renal death. DoSC: from the baseline average determination (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). ESKD: initiation of maintenance dialysis for at least 30 days, or renal transplantation, or an eGFR value of <15 mL/min/1.73 m^2 (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). Renal death: death in participants who have reached ESKD, died without initiating renal replacement therapy, and no other cause of death was determined via adjudication. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of the renal composite endpoint are presented.	Up to 12 weeks
Other	Renal Composite Endpoint	The renal composite endpoint included composite of doubling of serum creatinine (DoSC), end-stage kidney disease (ESKD), and renal death. DoSC: from the baseline average determination (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). ESKD: initiation of maintenance dialysis for at least 30 days, or renal transplantation, or an eGFR value of <15 mL/min/1.73 m^2 (sustained and confirmed by repeat central laboratory measure after at least 30 days and preferably within 60 days). Renal death: death in participants who have reached ESKD, died without initiating renal replacement therapy, and no other cause of death was determined via adjudication. Adjudication of these events by the EAC was performed in a blinded fashion. Event rate estimated based on the time to the first occurrence of the renal composite endpoint are presented.	Up to 26 weeks
Other	Liver Injury	Liver injury is defined as: i) a rise of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to 3 times above the upper limit of normal [ULN], or ii) a rise of total bilirubin to 2 times above the upper limit of normal [ULN].	Up to 12 weeks
Other	Liver Injury	Liver injury is defined as: i) a rise of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) to 3 times above the upper limit of normal [ULN], or ii) a rise of total bilirubin to 2 times above the upper limit of normal [ULN].	Up to 26 weeks
Other	Bleeding Events	All bleeding events, including major bleeding, non-major clinically relevant bleeding and minimal bleeding (for incidences only) will be assessed.	Up to 12 weeks
Other	Bleeding Events	All bleeding events, including major bleeding, non-major clinically relevant bleeding and minimal bleeding (for incidences only) will be assessed.	Up to 26 weeks
Primary	Change From Baseline in the KCCQ Clinical Summary Score	KCCQ was a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. KCCQ-clinical summary score was average of domains- physical limitation and total symptoms (average of symptom frequency and symptom burden), and transformed to a single score which ranged from 0 (worst) -100 (the best possible status), where the higher score reflected better health status.	Up to 12 weeks
Secondary	Change From Baseline in the Traditional Chinese Medicine Syndrome Score Scale (TCMSSS)	Traditional Chinese Medicine Syndrome Score is a instrument that quantifies symptoms. Lower TCM scores reflect better health status.	Up to 12 weeks
Secondary	Change in Exercise Capacity as Measured by the 6-Minutes-Walking-Test (6MWT) Distance	Change from baseline to week 12 in exercise capacity as measured by the distance walked in 6 minutes in standardised conditions. Change from baseline was defined as the distance walked in 6 minutes at week 12 minus the baseline value. Baseline value was defined as the last available measurement before start of treatment with randomised study medication.	Up to 12 weeks
Secondary	Change in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP)	Change from baseline to week 12 in N-terminal pro-brain natriuretic peptide (NT-proBNP). Baseline value was defined as the mean of all available measurements from the screening visit until start of treatment with randomised study medication.	Up to 12 weeks
Secondary	Change in Left Ventricular Systolic Function	Change in left ventricular ejection fraction is assessed by two-dimensional directed M-mode echocardiography.	Up to 12 weeks
Secondary	Change in Left Ventricular End-Diastolic Diameter	Change in left ventricular end-diastolic diameter is assessed by two-dimensional directed M-mode echocardiography.	Up to 12 weeks
Secondary	Change in Left Ventricular End-Systolic Diameter	Change in left ventricular end-systolic diameter is assessed by two-dimensional directed M-mode echocardiography.	Up to 12 weeks
Secondary	Change in Estimated Glomerular Filtration Rate from Baseline	Estimated glomerular filtration rate (eGFR) is calculated by the CKD-EPI equation.	Up to 12 weeks
Secondary	Change From Baseline in the KCCQ Clinical Summary Score	KCCQ was a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. KCCQ-clinical summary score was average of domains- physical limitation and total symptoms (average of symptom frequency and symptom burden), and transformed to a single score which ranged from 0 (worst) -100 (the best possible status), where the higher score reflected better health status.	Up to 26 weeks
Secondary	Change From Baseline in the Traditional Chinese Medicine Syndrome Score Scale (TCMSSS)	Traditional Chinese Medicine Syndrome Score is a instrument that quantifies symptoms. Lower TCM scores reflect better health status.	Up to 26 weeks