SHengXIaN-QuYu DEcoction in the Treatment of Heart Failure With Reduced Ejection Fraction (SHINE-HF)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure With Reduced Ejection Fraction
• Intervention / Treatment: Drug: ShengXian-QuYu Decoction; Other: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 564
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Mengxi Yang, Dr.; Phone Number: +8615120049452; Email: mxtezuka@163.com
• Study Contact Backup: Name: Jiang Liu, Dr.; Phone Number: +8619800361320; Email: 674754304@qq.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Recruiting
      • China-Japan Friendship hospital
      • Contact: Jiang Liu; Phone Number: +86 19800361320; Email: 674754301@qq.com
      • Principal Investigator: Jingyi Ren
    • Beijing, Beijing, China
      • Recruiting
      • Peking University People's Hospital
      • Contact: Ding Li; Phone Number: +86 18613818585; Email: rmhpy@outlook.com
      • Principal Investigator: Ding Li
    • Beijing, Beijing, China
      • Recruiting
      • Beijing Fengtai Hospital of Integrated Traditional Chinese and Western Medicine
      • Contact: Lingling Liu; Phone Number: +86 18801200210; Email: 329419791@qq.com
      • Principal Investigator: Lingling Liu
    • Beijing, Beijing, China
      • Recruiting
      • Changping District Traditional Chinese Medicine Hospital
      • Contact: Zhao Jin; Phone Number: +86 13426113311; Email: singledouya@163.com
      • Principal Investigator: Zhao Jin
    • Beijing, Beijing, China
      • Recruiting
      • Dongfang Hospital Affiliated to Beijing University of Chinese Medicine
      • Contact: Xiaoyun Cui; Phone Number: +86 13811890290; Email: you6171@126.com
      • Principal Investigator: Xiaoyun Cui
    • Beijing, Beijing, China
      • Recruiting
      • Huairou District Traditional Chinese Medicine Hospital of Beijing
      • Contact: Shaojun Chen; Phone Number: +86 13552301395; Email: 18910842603@163.com
      • Principal Investigator: Shaojun Chen
  • Hebei
    • Baoding, Hebei, China
      • Recruiting
      • Tangxian County Traditional Chinese Medicine Hospital
      • Contact: Jianfei Guan; Phone Number: +8613483208655; Email: 75821843@qq.com
      • Principal Investigator: Jianfei Guan
    • Qinhuangdao, Hebei, China
      • Recruiting
      • Funing Hospital of Traditional Chinese Medicine
      • Contact: Shi Li; Phone Number: +86 13001422602; Email: 358743873@qq.com
      • Principal Investigator: Shi Li
  • Henan
    • Gongyi, Henan, China
      • Recruiting
      • Gongyi City People's Hospital
      • Contact: Jijie Wang; Phone Number: +8613838199975‬; Email: 393190024@qq.com
      • Principal Investigator: Jijie Wang
  • Jiangsu
    • Yangzhou, Jiangsu, China
      • Recruiting
      • Yangzhou Tranditional Chinese Medicine Hospital
      • Contact: Xiaobin Wang; Phone Number: +86 18061178158; Email: 2336905303@qq.com
      • Principal Investigator: Xiaobin Wang
  • Shandong
    • Jining, Shandong, China
      • Recruiting
      • Jining Hospital of Traditional Chinese Medicine
      • Contact: Zhiyang Zhu; Phone Number: +86 18753768269; Email: zhuzhiyang136@126.com
      • Principal Investigator: Zhiyang Zhu
    • Qingdao, Shandong, China
      • Recruiting
      • The Affiliated Hospital of Qingdao University
      • Contact: Hui Xin; Phone Number: +86 18661801287; Email: xinhuiqy@163.com
      • Principal Investigator: Hui Xin
  • Shanxi
    • Changzhi, Shanxi, China
      • Recruiting
      • Heji Hospital Affiliated to Changzhi Medical College
      • Contact: Xiaojian Liu; Phone Number: +86 18035590665; Email: 787875739@qq.com
      • Principal Investigator: Xiaojian Liu
    • Changzhi, Shanxi, China
      • Recruiting
      • Shanxi Changzhi Hospital of Traditional Chinese Medicine
      • Contact: Meiling Shi; Phone Number: +86 13593286922; Email: czzyytnbsml1606@163.com
      • Principal Investigator: Meiling Shi
    • Changzhi, Shanxi, China
      • Recruiting
      • The Affiliated Hospital of Changzhi Institute of Traditional Chinese Medicine
      • Contact: Haijun Song; Phone Number: +86 15534566561; Email: 1549916295@qq.com
      • Principal Investigator: Haijun Song
  • Tianjin
    • Tianjin, Tianjin, China
      • Recruiting
      • Jixian Chinese Traditional Hospital
      • Contact: Baolong Yang; Phone Number: +86 13752702312; Email: 176121179@qq.com
      • Principal Investigator: Baolong Yang
  • Zhejiang
    • Linhai, Zhejiang, China
      • Recruiting
      • Linhai Hospital of Traditional Chinese Medicine
      • Contact: Yingjing Song; Phone Number: +86 13646769521; Email: hyysyj@126.com
      • Principal Investigator: Yingjing Song

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ShengXian-QuYu Decoction; Patients will be randomized 1:1 to either ShengXian-QuYu Decoction or placebo. "ShengXian-QuYu Decoction" (calculated by a medicine): 30g of Astragalus membranaceus (Huangqi), 12g of Cornus officinalis (Shanzhuyu), 9g of Talinum paniculatum (Jacq.) Gaertn. (Hongshen), 12g of Rhizoma Anemarrhena (Zhimu), 8g of Rhizoma Cimicifugae (Shengma), 8g of Radix Bupleuri (Chaihu), 10g of Platycodon grandiflorum (Jiegeng), 10g of Rhizoma Sparganii (Sanleng), 9g of Rhizoma Curcumae (Ezhu), 3g of Whitmania pigra Whitman (Shuizhi).	Drug: ShengXian-QuYu Decoction; Specification: 30ml/bag, given twice daily, per oral use.
Placebo Comparator: placebo; Placebo matching ShengXian-QuYu Decoction	Other: Placebo; Placebo matching ShengXian-QuYu Decoction, 30ml/bag, given twice daily, per oral use.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
Change in Estimated Glomerular Filtration Rate from Baseline	Estimated glomerular filtration rate (eGFR) is calculated by the CKD-EPI equation.	Up to 12 weeks
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
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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: China-Japan Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2023
• Primary Completion (Estimated): April 30, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: October 8, 2022
• First Submitted That Met QC Criteria: October 13, 2022
• First Posted (Actual): October 18, 2022

Study Record Updates

• Last Update Posted (Estimated): February 6, 2024
• Last Update Submitted That Met QC Criteria: February 2, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Quality of life; Randomized; Biomarkers; Heart failure with reduced ejection fraction; Multicenter; Symtoms; ShengXian-QuYu Decoction
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 2022-NHLHCRF-LX-02-0102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No