Shengxian Quyu Decoction in the Treatment of Heart Failure With Reduced Ejection Fraction

Study Overview
=================
Brief 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.

Detailed Description
-----------------
This is a multicenter, prospective, randomised, placebo-controlled study in patients with chronic 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 therapy. The effect of Shengxian Quyu Decoctionon 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.

Official Title
-----------------
Effects of Shengxian Quyu Decoction on Quality of Life, Symptoms, and Biomarkers in Heart Failure Patients With Reduced Ejection Fraction: A Multicenter, Randomized Clinical Trial.

Conditions
-----------------
Heart Failure With Reduced Ejection Fraction

Intervention / Treatment
-----------------
* Drug: Shengxian Quyu Decoction
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female, aged ≥18 years at the time of consent. Established documented diagnosis of symptomatic HFrEF (NYHA functional class II-IV). LVEF<40%. 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. Provision of signed informed consent prior to any study specific procedures. Exclusion Criteria: 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. Uncontrolled severe arrhythmia. Planned to undergo heart transplantation or device implantation. 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). Severe infection. eGFR <30 mL/min/1.73 m^2 by CKD-EPI. Active malignancy requiring treatment at the time of visit 1. 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. 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. Systolic blood pressure < 90 mmHg, or systolic blood pressure ≥ 180 mmHg, or diastolic blood pressure ≥ 110 mmHg on 2 consecutive measurements. Heart failure due to infiltrative cardiomyopathies(cardiac amyloidosis, etc.), fulminant myocarditis, constrictive pericarditis. Participation in another clinical study. 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Shengxian Quyu Decoction<br>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<br>* Specification: 30ml/bag, given twice daily, per oral use.<br>|
| Placebo Comparator: placebo<br>Placebo matching Shengxian Quyu Decoction | Other: Placebo<br>* Placebo matching Shengxian Quyu Decoction, 30ml/bag, given twice daily, per oral use.<br>|

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 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 | 
| 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Quality of Life, Shengxian Quyu Decoction, Heart failure with reduced ejection fraction, Symtoms, Biomarkers, Multicenter, Randomized