This study will evaluate whether adding Yiqi Fumai lyophilized injection to stable guideline-directed treatment improves symptoms, physical limitations, and NT-proBNP in adults with stable chronic heart failure caused by coronary heart disease. About 100 participants at four hospitals in China will receive 8 vials of Yiqi Fumai once daily by intravenous infusion for a planned 10 days. The two main outcomes will be the proportion of participants with at least a 5-point improvement in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score and the proportion with at least a 30% decrease in NT-proBNP at the Day 11 end-of-treatment visit after the 10-day treatment course. Participants will be followed through Day 90 for heart function, exercise capacity, quality of life, safety, healthcare use, costs, and clinical events. A randomly selected subgroup of 50 participants will provide paired blood samples on Day 1 before the first infusion and on Day 11 at the end-of-treatment visit for exploratory transcriptomic, proteomic, and metabolomic analyses.
This record covers the prospective interventional component of a broader integrated research program. The registered component is a multicenter, prospective, open-label, single-arm performance-goal study in 100 hospitalized adults aged 40 to 80 years with stable chronic heart failure with reduced ejection fraction caused by coronary heart disease, NYHA class II or III symptoms, left ventricular ejection fraction of 40% or less, NT-proBNP of at least 450 pg/mL, and Qi and Yin deficiency syndrome. All participants will receive Yiqi Fumai lyophilized injection in addition to stable guideline-directed medical therapy. The study drug will be administered as 8 vials once daily, diluted in 250 mL of 0.9% sodium chloride, by intravenous infusion at 35 to 40 drops per minute for a planned 10 days. Clinically necessary discharge, transfer, treatment modification, or rescue therapy will not be delayed to complete study procedures. The co-primary outcomes are Day 11 KCCQ-CSS response and Day 11 NT-proBNP response, both measured at the end-of-treatment visit, targeted 24 +/- 4 hours after initiation of the 10th infusion; no study drug is infused on Day 11. KCCQ-CSS response is generally defined as an increase of at least 5 points from baseline. NT-proBNP response is defined as a decrease of at least 30% from baseline using paired central-laboratory results. Death, heart-failure rehospitalization, major rescue therapy, or inability to complete assessment because of worsening heart failure before Day 11 is counted as nonresponse. The KCCQ-CSS performance goal is p0=50% with p1=65%, and the NT-proBNP performance goal is p0=45% with p1=60%. Testing follows a prespecified fixed order and intersection-union principle; both outcomes must pass for overall co-primary success. Follow-up assessments occur at Day 30 and Day 90. A prespecified subgroup of 50 participants, randomly selected within center and NYHA strata, will undergo paired Day 1 pre-infusion and Day 11 end-of-treatment multi-omics sampling. The broader protocol also includes a separate retrospective comparative cohort of 200 patients for external triangulation and economic modeling; those retrospective patients are not part of the enrollment or design entered in this interventional record.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
100
Eight vials (0.65 g per vial; total 5.2 g) are diluted in 250 mL of 0.9% sodium chloride and administered by intravenous infusion once daily at 35 to 40 drops per minute for a planned 10 consecutive days. The product is manufactured by Tianjin Tasly Pride Pharmaceutical Co., Ltd. and is approved in China under NMPA approval number Z20060463. Each infusion is preceded by verification of indication, allergy history, vital signs, volume status, diluent, compatibility, product appearance, expiry date, and emergency readiness. Symptoms, heart rate, blood pressure, respiratory rate, and oxygen saturation are monitored at 15 minutes, 30 minutes, and at the end of infusion.
Participants continue guideline-directed medical therapy appropriate to their clinical condition. Core background therapies should generally have been stable for at least 2 weeks before Day 0. Any modification required for safety or clinical deterioration takes priority and is fully documented, including daily doses of ARNI/ACEI/ARB, beta-blockers, mineralocorticoid receptor antagonists, SGLT2 inhibitors, loop diuretics, and other heart-failure therapies.
Guangdong Provincial Hospital of Chinese Medicine
Guangzhou, Guangdong, China
The First Affiliated Hospital of Henan University of Chinese Medicine
Zhengzhou, Henan, China
Guang'anmen Hospital Jinan Hospital, China Academy of Chinese Medical Sciences
Jinan, Shandong, China
The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine
Tianjin, Tianjin Municipality, China
Percentage of Participants With a KCCQ-CSS Response at Day 11
A responder generally has an increase of at least 5 points in the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) from baseline to Day 11.Death, heart-failure rehospitalization, major rescue therapy, inability to complete the questionnaire because of worsening heart failure, or a missing Day 11 primary assessment in the full analysis set is counted as nonresponse. The official Simplified Chinese KCCQ-23 is administered independently and CSS is derived centrally. The prespecified performance goal is p0=50%; with n=100, at least 59 responders are required by the one-sided exact binomial rule.
Time frame: Baseline (Day 1 before the first infusion) to Day 11, 24 +/- 4 hours after initiation of the 10th infusion (no Day 11 infusion)
Percentage of Participants With an NT-proBNP Response at Day 11
A responder has a decrease of at least 30% in NT-proBNP from baseline, calculated as \[(baseline value - Day 11 value) / baseline value\] x 100. The primary analysis uses paired central-laboratory results obtained with the same specimen type, platform, unit, calibration, and quality-control procedures. Death, heart-failure rehospitalization, major rescue therapy, inability to complete assessment because of worsening heart failure, or a missing Day 11 primary assessment in the full analysis set is counted as nonresponse. The prespecified performance goal is p0=45%; with n=100, at least 54 responders are required after the KCCQ-CSS test has passed.
Time frame: Baseline (Day 1 before the first infusion) to Day 11, 24 +/- 4 hours after initiation of the 10th infusion (no Day 11 infusion)
Change From Baseline in KCCQ-CSS
KCCQ-CSS is derived centrally from the official Simplified Chinese KCCQ-23. Change from baseline is summarized as a continuous measure, together with the proportions achieving increases of at least 5, 10, and 15 points. Day 30 is the key supportive time point and Day 90 assesses persistence.
Time frame: Baseline (Day 1 before the first infusion); Day 11 (end of treatment; no infusion); Day 30 +/- 3 days; Day 90 +/- 7 days
Change and Percent Change From Baseline in NT-proBNP
Absolute change, percent change, and the proportion with a decrease of at least 30% are summarized. Day 30 is the key supportive time point. BNP and NT-proBNP values are not combined.
Time frame: Baseline (Day 1 before the first infusion); Day 11 (end of treatment; no infusion); Day 30 +/- 3 days; Day 90 +/- 7 days
Percentage of Participants With a Clinical Response in Qi and Yin Deficiency Syndrome
The syndrome-score reduction rate is calculated as \[(baseline score - follow-up score) / baseline score\] x 100. A reduction of at least 70% is classified as markedly effective, 30% to 69% as effective, and less than 30% as ineffective. Total response equals markedly effective plus effective.
Time frame: Baseline (Day 1) to Day 11, Day 30 +/- 3 days, and Day 90 +/- 7 days
Change From Baseline in Left Ventricular Ejection Fraction
Left ventricular ejection fraction is measured by the modified biplane Simpson method. Original DICOM images are centrally reviewed by readers blinded to visit time and clinical outcomes; the central value is the supportive primary result for this measure.
Time frame: Baseline to Day 90 +/- 7 days
Change From Baseline in Left Ventricular End-Diastolic Diameter
Left ventricular end-diastolic diameter is obtained by standardized transthoracic echocardiography with central review of DICOM images.
Time frame: Baseline to Day 90 +/- 7 days
Percentage of Participants With Improvement in NYHA Functional Class
Improvement is defined as a decrease of at least one NYHA functional class from baseline without heart-failure rehospitalization or death before the assessment.
Time frame: Baseline (Day 1) to Day 11, Day 30 +/- 3 days, and Day 90 +/- 7 days
Change From Baseline in Minnesota Living With Heart Failure Questionnaire Total Score
The total score change is summarized, together with the proportions achieving a decrease of at least 5 points or at least 20%. Day 10 is descriptive; Days 30 and 90 are supportive.
Time frame: Baseline (Day 1); Day 11; Day 30 +/- 3 days; Day 90 +/- 7 days
Change From Baseline in 6-Minute Walk Distance
Change in 6-minute walk distance is summarized as a continuous measure and as the proportion with an increase of at least 15 meters. Day 90 is the key supportive time point. Tests are performed under standardized conditions when clinically safe; an unperformed test is not assigned a value of zero.
Time frame: Baseline (Day 1); Day 11; Day 30 +/- 3 days; Day 90 +/- 7 days
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