Chronic Heart Failure, Coronary Heart Disease (CHD), Heart Failure With Reduced Ejection Fraction (HFrEF)
Conditions
Keywords
Yiqi Fumai lyophilized injection, chronic left ventricular dysfunction, NYHA class II; NYHA class III, Qi and Yin deficiency syndrome, traditional Chinese medicine injection, pharmacoeconomic evaluation, multi-omics
Brief summary
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.
Detailed description
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.
Interventions
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.
OTHERStable Guideline-Directed Medical Therapy
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.
Sponsors
China Academy of Chinese Medical Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All enrolled participants receive Yiqi Fumai lyophilized injection plus stable guideline-directed medical therapy. Outcomes are evaluated against prespecified performance goals rather than a concurrent control group.
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age 40 to 80 years, inclusive, of any sex. 2. Confirmed coronary heart disease or chronic coronary syndrome according to the protocol-defined criteria, supported by at least one verifiable item such as prior myocardial infarction, prior PCI or CABG, at least 50% stenosis in a major epicardial coronary artery on angiography or coronary CT angiography, FFR of 0.80 or less, iFR of 0.89 or less, or imaging evidence of prior ischemic infarction or scar with corresponding coronary atherosclerosis. 3. Heart failure judged to be caused primarily by coronary heart disease, with objective evidence supporting an ischemic cause and no more likely major nonischemic cause. 4. A documented diagnosis of chronic heart failure for at least 3 months, or verifiable persistent heart-failure treatment with structural or functional cardiac abnormality; and stable chronic heart failure with reduced ejection fraction at Day 0, defined by LVEF of 40% or less, NT-proBNP of at least 450 pg/mL, and NYHA class II or III. 5. Clinical stability at Day 0: no initiation or intensification of intravenous inotropes, vasoactive drugs, mechanical ventilation, mechanical circulatory support, or ultrafiltration within the previous 72 hours; no increase in the daily dose of intravenous loop diuretic within the previous 24 hours; no acute pulmonary edema, worsening resting hypoxemia, or hypoperfusion; no clinically significant progressive deterioration in blood pressure or renal function; and core guideline-directed therapies generally stable for at least 2 weeks. A patient with acute decompensated heart failure during the current hospitalization may not later transition into this study. 6. Qi and Yin deficiency syndrome according to the protocol-defined traditional Chinese medicine criteria, requiring qualifying manifestations of both Qi deficiency and Yin deficiency, at least one secondary symptom, and compatible tongue and pulse findings. 7. The participant or legally authorized representative can understand the study, participates voluntarily, and signs the informed consent form before any study-specific procedure. 8. Able to complete efficacy, safety, quality-of-life, cost, and biospecimen assessments required by the protocol. 9. For women of childbearing potential, a negative urine or serum pregnancy test during screening; equivocal results or delayed menstruation require repeat testing.
Exclusion criteria
1. Acute heart failure, acute decompensation of chronic heart failure, cardiogenic shock, malignant arrhythmia, acute respiratory failure, acute pulmonary edema, need for mechanical ventilation or mechanical circulatory support, or another critical condition requiring immediate rescue treatment. 2. Acute coronary syndrome or acute myocardial infarction within 1 month before enrollment if the investigator determines that it will materially affect efficacy, safety, or omics assessments. 3. PCI or CABG within 3 months before screening; CRT implantation or upgrade within 6 months before screening; or a definite plan for PCI, CABG, or CRT implantation or upgrade within the next 6 months. Prior CRT is not an absolute exclusion if it was performed at least 6 months earlier, device settings and clinical status are stable, and no major upgrade or parameter change is planned. 4. NYHA class IV, clinical instability, or inability to safely complete the short-term study procedures. 5. Heart failure caused primarily by severe valvular heart disease, primary cardiomyopathy, congenital heart disease, pericardial disease, cor pulmonale, severe pulmonary hypertension, thyroid dysfunction, severe anemia, infective endocarditis, or another noncoronary cause. 6. Severe hepatic, renal, or hematologic disease, including ALT or AST greater than 3 times the upper limit of normal, eGFR less than 30 mL/min/1.73 m2, dialysis, severe anemia, or another condition judged unsuitable by the investigator. 7. Markedly uncontrolled glucose metabolism: screening HbA1c of at least 9.0%; or confirmed fasting plasma glucose of at least 13.9 mmol/L after excluding acute infection, stress, and short-term glucocorticoid effects; or diabetic ketoacidosis, hyperosmolar hyperglycemic state, or another condition requiring urgent intensive glucose-lowering treatment. A single elevated random glucose value alone is not sufficient for exclusion. 8. Markedly uncontrolled blood pressure or hypotension risk: systolic blood pressure of at least 180 mmHg, diastolic blood pressure of at least 110 mmHg, systolic blood pressure below 90 mmHg, or persistently repeated diastolic blood pressure below 50 mmHg accompanied by dizziness, syncope, oliguria, cold extremities, hypoperfusion, or symptomatic hypotension. 9. Severe intracerebral hemorrhage, severe sequelae of cerebral infarction, severe cognitive impairment, psychiatric disorder, aphasia, or another condition that interferes with questionnaire assessment or follow-up data collection. 10. Active malignancy, severe infection, active autoimmune disease, or expected survival of less than 6 months. 11. Pregnancy or breastfeeding. 12. Known allergy to Yiqi Fumai lyophilized injection, red ginseng, Ophiopogon japonicus, Schisandra chinensis, or any excipient; or a prior serious adverse reaction to a similar product. 13. Participation in another clinical study that, in the investigator's judgment, may affect efficacy, safety, adherence, or economic evaluation in this study. 14. Current use, with planned continuation during the study, or inability to discontinue, of a Qi-tonifying and Yin-nourishing Chinese herbal decoction or proprietary Chinese medicine with effects overlapping those of the study drug. 15. Any other condition that the investigator considers unsuitable for participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a KCCQ-CSS Response at Day 11 | Baseline (Day 1 before the first infusion) to Day 11, 24 +/- 4 hours after initiation of the 10th infusion (no Day 11 infusion) | 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. |
| Percentage of Participants With an NT-proBNP Response at Day 11 | Baseline (Day 1 before the first infusion) to Day 11, 24 +/- 4 hours after initiation of the 10th infusion (no Day 11 infusion) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in KCCQ-CSS | Baseline (Day 1 before the first infusion); Day 11 (end of treatment; no infusion); Day 30 +/- 3 days; Day 90 +/- 7 days | 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. |
| Change and Percent Change From Baseline in NT-proBNP | Baseline (Day 1 before the first infusion); Day 11 (end of treatment; no infusion); Day 30 +/- 3 days; Day 90 +/- 7 days | 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. |
| Percentage of Participants With a Clinical Response in Qi and Yin Deficiency Syndrome | Baseline (Day 1) to Day 11, Day 30 +/- 3 days, and Day 90 +/- 7 days | 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. |
| Change From Baseline in Left Ventricular Ejection Fraction | Baseline to Day 90 +/- 7 days | 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. |
| Change From Baseline in Left Ventricular End-Diastolic Diameter | Baseline to Day 90 +/- 7 days | Left ventricular end-diastolic diameter is obtained by standardized transthoracic echocardiography with central review of DICOM images. |
| Percentage of Participants With Improvement in NYHA Functional Class | Baseline (Day 1) to Day 11, Day 30 +/- 3 days, and Day 90 +/- 7 days | Improvement is defined as a decrease of at least one NYHA functional class from baseline without heart-failure rehospitalization or death before the assessment. |
| Change From Baseline in Minnesota Living With Heart Failure Questionnaire Total Score | Baseline (Day 1); Day 11; Day 30 +/- 3 days; Day 90 +/- 7 days | 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. |
| Change From Baseline in 6-Minute Walk Distance | Baseline (Day 1); Day 11; Day 30 +/- 3 days; Day 90 +/- 7 days | 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. |
Countries
China
Contacts
CONTACTLianxin Wang, PhD
CONTACTBai Du, PhD
PRINCIPAL_INVESTIGATORLianxin Wang
Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences
Outcome results
None listed