Study on Heart Failure with Preserved Ejection Fraction with Qishen Granules

A Randomized, Double-blind, Placebo-controlled Study on the Treatment of Heart Failure with Preserved Ejection Fraction with Qishen Granules Based on Cardiopulmonary Exercise Test

With the cardiopulmonary exercise testing as the primary outcome, the study aims to evaluate the efficacy of Qishen Granules on cardiac function, quality of life and biomarker level of patients with heart failure with preserved ejection fraction (HFpEF), which will provide evidence for the treatment of HFpEF with traditional Chinese medicine.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure with Preserved Ejection Fraction
• Intervention / Treatment: Drug: Qishen Granules; Drug: Placebo

Detailed Description

Heart failure with preserved ejection fraction (HFpEF) is common and is associated with high morbidity and mor-tality in China. Studies have shown that traditional Chinese medicine (TCM) combined with conventional Western medicine has a good effect on improving exercise tolerance and quality of life in patients with HFpEF, but there are still some shortcomings that limit the reliability and extrapolation of results. Based on TCM theory and our decades of experience, we developed Qishen Granules for therapeutic use in the treatment of HFpEF. The good effect of Qishen Granules in patients with heart failure has been clinically verified before. In this study, cardiopulmonary exercise test (CPET) was used to evaluate the peak oxygen consumption (peak VO2), which is the gold standard assessment of aerobic capacity. Therefore, we selected VO2 peak as the primary outcome. At the same time, we conducted a preliminary assessment of the efficacy of Qishen Granules in improving the quality of life in patients with HFpEF, using Kansas City Cardiomyopathy Questionnaire (KCCQ) as the secondary outcome, and combined with other CPET indicators, echocardiographic measures, NT-pro BNP level, growth STimulation expressed gene 2 (ST2), biomarkers of liver and kidney function, and TCM Four-Dimensional Diagnostic Information Scale (TCMFDIS) to objectively, accurately, and comprehensively evaluate the efficacy and safety of Qishen Granules in improving quality of life and exercise capacity in patients with HFpEF.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Lei Wang, doctorate; Phone Number: 8620-81887233-3280; Email: Dr.wanglei@139.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510120
      • Recruiting
      • Guangdong Provincial Hospital of Chinese Medicine
      • Contact: Lei Wang, M.D; Phone Number: 8620-81887233-32801; Email: Dr.wanglei@139.com
    • Guangzhou, Guangdong, China, 510120
      • Recruiting
      • WangLei
      • Contact: Lei / Wang, doctorate; Phone Number: +8613724078381; Email: Dr.wanglei@139.com
      • Contact: Shuai / Mao, doctorate; Phone Number: 86-20-81887233-32801; Email: maoshuaitcm@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Sign the informed consent form
2. Age 18-85 years old
3. Heart failure was diagnosed ≥ 3 months before enrollment, The heart function classification II-IV of New York Heart Association (NYHA)
4. has ≥ 1 of the following: 1） Structural heart disease (left atrial enlargement and/or left ventricular hypertrophy) recorded by echocardiography at the time of enrollment；2）Hospitalization due to heart failure within 12 months before enrollment
5. Retention of ejection fraction: left ventricular ejection fraction (LVEF)≥50% (Echocardiography)
6. Increase of NTpro-BNP (patients without atrial fibrillation>220pg/mL, patients with atrial fibrillation>660pg/mL
7. If diuretics are being administered orally, the dose must be stable for ≥ 2 weeks before inclusion in the study
8. At the time of randomization, it was clinically stable without signs of decompensation of cardiac failure (judged by the investigator)

Exclusion Criteria:

1. Patients with decompensated heart failure
2. Glomerular filtration rate (eGFR)<30mL/min/1.73m 2
3. Atrial fibrillation or atrial flutter with obvious liver disease or ALT, AST 3 times higher than the upper limit of normal
4. Symptomatic hypotension or systolic blood pressure (SBP)<100mmHg at the time of inclusion or baseline
5. Resting heart rate recorded by echocardiography at the time of screening>110bpm
6. Currently participating in another research equipment or drug test, or less than 30 days after the completion of another research equipment or drug test or receiving other research treatment. Patients participating in purely observational trials will not be excluded
7. At present, people who are taking traditional Chinese medicine or Chinese patent medicine with similar effect to Qishen Granules
8. Be allergic to any component of Qishen granules (astragalus membranaceus, salvia miltiorrhiza, and black aconite)
9. Patients who refuse to sign the informed consent form or estimate poor compliance and women who are pregnant, nursing or planning to become pregnant during the trial

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Qishen Granules; On the basis of standardized drug treatment for HFpEF, participants who met the inclusion criteria were randomly given Qishen Granule intervention on the day of inclusion, taking it twice a day for 90 days.	Drug: Qishen Granules; One package per time, twice a day, 90 days of treatment
Placebo Comparator: Placebo; On the basis of standardized drug treatment for HFpEF, participants who met the inclusion criteria were randomly given placebo granules on the day of inclusion, which were taken twice a day for 90 days (the placebo was basically the same as Qishen granules in terms of appearance, shape, color, taste, etc.)	Drug: Placebo; One package per time, twice a day, 90 days of treatment (the placebo was basically the same as Qishen granules in terms of appearance, shape, color, taste, etc.)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in peak oxygen uptake within the average minute (PeakVO2) compared to baseline on day 90	Measure the efficiency of peak oxygen intake by combining oxygen volume and time to report PeakVO2 in ml/min	At enrollment versus at day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Mitral valve diastolic blood flow velocity (E) and Mitral annulus lateral and septal motion velocity (e') compared to baseline on day 90	Measure the blood flow velocity or motion velocity of specific areas in cm/s	At enrollment versus at day 90
Changes in E/e' ratio compared to baseline on day 90	E/e' ratio	At enrollment versus at day 90
Changes in Left Atrial Volume index (LAVI) compared to baseline on day 90	Left atrial volume (estimated from echocardiography measurement data) and body surface area (estimated based on height and weight) will be combined to report LAVI in ml/m^2	At enrollment versus at day 90
Changes in Left ventricular mass index (LVMI) compared to baseline on day 90	Left ventricle mass (estimated from echocardiography measurement data) and body surface area (estimated based on height and weight) will be combined to report LVMI in g/m^2	At enrollment versus at day 90
Changes in Score of Kansas City Cardiomyopathy Questionnaire (KCCQ) compared to baseline on day 90	Calculate the scores of the KCCQ questionnaire	At enrollment versus at day 90
Changes in blood N terminal pro B type natriuretic peptide(NT-proBNP) compared to baseline on day 90	Level of blood NT-proBNP in mmol/L	At enrollment versus at day 90
Changes in blood Growth STimulation expressed gene 2(ST2) compared to baseline on day 90	Level of blood ST2 in mmol/L	At enrollment versus at day 90
Changes in blood urea compared to baseline on day 90	Level of blood urea in mmol/L	At enrollment versus at day 90
Changes in blood creatinine compared to baseline on day 90	Level of blood creatinine in mmol/L	At enrollment versus at day 90

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Aspartate aminotransferase(AST) compared to baseline on day 90	Level of blood AST in mmol/L	At enrollment versus at day 90
Changes in Alanine aminotransferase(ALT) compared to baseline on day 90	Level of blood ALT in mmol/L	At enrollment versus at day 90
Number of participants with treatment-related adverse events	Assess the incidence of treatment-related adverse events	At enrollment versus at day 90

Collaborators and Investigators

• Sponsor: Guangdong Provincial Hospital of Traditional Chinese Medicine
• Investigators: Study Director: Lei Wang, doctorate, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: June 2, 2022
• First Submitted That Met QC Criteria: April 17, 2024
• First Posted (Actual): April 22, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 15, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Cardiopulmonary Exercise Test; Heart Failure with Preserved Ejection Fraction; Qishen Granules
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: BF-2022-121

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

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