Study on Heart Failure with Preserved Ejection Fraction with Qishen Granules

Official title

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

Overview

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.

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.

Interventions

• Drug Qishen Granules
  One package per time, twice a day, 90 days of treatment
• 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.)

Primary outcome measures

• Changes in peak oxygen uptake within the average minute (PeakVO2) compared to baseline on day 90 [Time frame: At enrollment versus at day 90]

Secondary outcome measures (9)

• Changes in Mitral valve diastolic blood flow velocity (E) and Mitral annulus lateral and septal motion velocity (e') compared to baseline on day 90 [Time frame: At enrollment versus at day 90]
• Changes in E/e' ratio compared to baseline on day 90 [Time frame: At enrollment versus at day 90]
• Changes in Left Atrial Volume index (LAVI) compared to baseline on day 90 [Time frame: At enrollment versus at day 90]
• Changes in Left ventricular mass index (LVMI) compared to baseline on day 90 [Time frame: At enrollment versus at day 90]
• Changes in Score of Kansas City Cardiomyopathy Questionnaire (KCCQ) compared to baseline on day 90 [Time frame: At enrollment versus at day 90]
• Changes in blood N terminal pro B type natriuretic peptide(NT-proBNP) compared to baseline on day 90 [Time frame: At enrollment versus at day 90]
• Changes in blood Growth STimulation expressed gene 2(ST2) compared to baseline on day 90 [Time frame: At enrollment versus at day 90]
• Changes in blood urea compared to baseline on day 90 [Time frame: At enrollment versus at day 90]
• Changes in blood creatinine compared to baseline on day 90 [Time frame: At enrollment versus at day 90]

Eligibility criteria

Inclusion criteria

• Sign the informed consent form
• Age 18-85 years old
• Heart failure was diagnosed ≥ 3 months before enrollment, The heart function classification II-IV of New York Heart Association (NYHA)
• 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
• Retention of ejection fraction: left ventricular ejection fraction (LVEF)≥50% (Echocardiography)
• Increase of NTpro-BNP (patients without atrial fibrillation>220pg/mL, patients with atrial fibrillation>660pg/mL
• If diuretics are being administered orally, the dose must be stable for ≥ 2 weeks before inclusion in the study
• At the time of randomization, it was clinically stable without signs of decompensation of cardiac failure (judged by the investigator)

Exclusion criteria

• Patients with decompensated heart failure
• Glomerular filtration rate (eGFR)<30mL/min/1.73m 2
• Atrial fibrillation or atrial flutter with obvious liver disease or ALT, AST 3 times higher than the upper limit of normal
• Symptomatic hypotension or systolic blood pressure (SBP)<100mmHg at the time of inclusion or baseline
• Resting heart rate recorded by echocardiography at the time of screening>110bpm
• 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
• At present, people who are taking traditional Chinese medicine or Chinese patent medicine with similar effect to Qishen Granules
• Be allergic to any component of Qishen granules (astragalus membranaceus, salvia miltiorrhiza, and black aconite)
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

China · 2 centers

• Guangdong Provincial Hospital of Chinese Medicine — Guangzhou
• WangLei — Guangzhou

Publications

• Chen H, Li Z, Su M, Song G, Guo S, Feng W, Chen W, Li C, Wang L, Wang W. Efficacy and safety of Qishen granule for treating heart failure with preserved ejection fraction: a study protocol for a multicenter, randomized, double-blind, placebo-controlled trial. BMC Complement Med Ther. 2025 Aug 6;25(1):298. doi: 10.1186/s12906-025-05029-z. PMID 40770799

Identifiers

NCT: NCT06377761 · BF-2022-121

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗