A Two-Center Retrospective Comparative Cohort Study and Pharmacoeconomic Evaluation of Yiqi Fumai Lyophilized Injection in Coronary Heart Disease-Related Heart Failure With Reduced Ejection Fraction, NYHA Class II or III, and Qi and Yin Deficiency Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 200
- 试验地点
- 2
- 主要终点
- Total Direct Medical Cost From Time Zero Through the End of the Index Hospitalization
研究概览
简要总结
This two-center retrospective cohort study will use de-identified electronic health records from June 1, 2021 through June 1, 2026 to compare patients with coronary heart disease-related chronic left ventricular dysfunction or chronic heart failure and Qi and Yin deficiency syndrome who initiated Yiqi Fumai lyophilized injection within 24 hours after a common time zero with eligible patients who did not initiate the drug within 24 hours. Treatment was determined during routine care and was not assigned by the researchers. The planned cohort includes 200 randomly sampled records, comprising 150 initiators and 50 non-initiators. The primary economic outcome is total direct medical cost during the index hospitalization, and the primary comparative-effectiveness outcome is heart-failure-related rehospitalization within 90 days after time zero. Baseline differences will be addressed primarily using propensity-score overlap weighting.
详细描述
This standalone record covers only the retrospective real-world comparative cohort component of a broader integrated research program. Electronic health records with index dates from June 1, 2021 through June 1, 2026 will be obtained from the Jinan and Tianjin study centers. Follow-up information for the retrospective primary outcomes will be ascertained through September 1, 2026. Time zero is the first point at which all verifiable eligibility criteria are met and baseline variables can be reconstructed. The treatment strategies are initiation of Yiqi Fumai lyophilized injection within 24 hours after time zero and no initiation within 24 hours after time zero. Future cumulative treatment duration is not used to define baseline exposure. Patients are not excluded from the primary intention-to-treat analogue solely because treatment subsequently lasted less than 7 days, the 10-day course was not completed, treatment was discontinued, or treatment crossover occurred. Actual dose, duration, discontinuation, completion, and crossover are recorded for adherence descriptions and prespecified per-protocol, landmark, time-dependent, or marginal structural model sensitivity analyses.
The fixed sample includes 200 patients: 150 initiators and 50 non-initiators, with each center contributing 75 initiators and 25 non-initiators. All eligible index hospitalizations will first be enumerated and deduplicated, retaining the first eligible index hospitalization for patients with multiple records. Four sampling strata will then be formed by study center and 24-hour treatment strategy. Simple random sampling without replacement will be performed within each stratum using a prespecified random seed. The screening flow, random seed, and reasons for non-inclusion will be retained.
The two domain-specific primary outcomes are analyzed separately without a joint success criterion, hierarchy, or performance goal. The primary economic outcome is total direct medical cost from time zero through discharge from the index hospitalization or in-hospital death. The primary comparative-effectiveness outcome is the first heart-failure-related rehospitalization within 90 days after time zero and after discharge from the index hospitalization, with death treated as a competing risk. The primary causal estimand is the average treatment effect in the overlap population. Propensity-score overlap weighting will include prespecified baseline covariates measured at or before time zero. Balance, overlap, positivity, extreme weights, and effective sample size will be evaluated. IPTW, matching, outcome regression, time-dependent analyses, marginal structural models, and 72-hour and Day-7 landmark analyses will be used as appropriate in sensitivity analyses.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The index date was from June 1, 2021 through June 1, 2026, the patient received inpatient or systematic clinical care at a participating center, and the patient was 40 to 80 years of age at time zero, with no restriction by sex.
- •The medical record supports protocol-defined coronary heart disease-related chronic left ventricular dysfunction or coronary heart disease with chronic heart failure.
- •The record contains sufficient information on functional class, echocardiography, BNP or NT-proBNP, medications, treatment course, laboratory tests, direct medical costs for the index hospitalization, heart-failure-related rehospitalization through 90 days, death, and follow-up for the prespecified analyses.
- •Qi and Yin deficiency syndrome or a related Qi-and-Yin-deficiency pattern can be determined from the medical record according to the prespecified adjudication rules.
- •The record is eligible for research use under ethics and data-governance requirements and can be de-identified before analysis; a waiver of informed consent must be documented when applicable.
- •The index date, first treatment date and time, daily and cumulative dose, treatment duration, discontinuation, completion, and crossover can be verified when Yiqi Fumai lyophilized injection was used.
- •Time zero, eligibility, and baseline variables can be reliably reconstructed, and initiation or non-initiation of Yiqi Fumai lyophilized injection within 24 hours after time zero can be clearly classified.
- •Prespecified baseline covariates can be abstracted, including age, sex, body mass index, history and grade of hypertension, cardiovascular risk, smoking, alcohol use, antihypertensive treatment, NYHA class, LVEF, BNP or NT-proBNP, heart-failure duration, comorbidities, guideline-directed medical therapy, diuretic intensity, baseline cost, and study center.
- •Acute conditions after time zero, treatment crossover, rescue treatment, and documented Chinese medicines or nonpharmacologic traditional Chinese medicine therapies, including their indication and start and stop dates, can be abstracted. Post-baseline variables will not be included in the baseline propensity-score model.
排除标准
- •Critical diagnostic, index, exposure, outcome, or cost information is missing to an extent that prevents eligibility classification or the prespecified analysis.
- •Evidence supporting coronary heart disease is insufficient, or heart failure is caused primarily by a noncoronary condition.
- •Acute myocardial infarction, acute coronary syndrome, cardiogenic shock, or another critical illness dominates the index episode.
- •Time zero cannot be reliably reconstructed, or initiation or non-initiation of Yiqi Fumai lyophilized injection within 24 hours after time zero cannot be clearly classified. Otherwise, patients will not be excluded from the primary analysis solely because subsequent treatment lasted less than 7 days, a 10-day course was not completed, treatment was discontinued, or crossover occurred. Patients who initiated the drug after 24 hours remain assigned to the non-initiation strategy in the primary intention-to-treat analogue.
- •Another Qi-tonifying and Yin-nourishing Chinese medicine injection, decoction, or proprietary Chinese medicine with overlapping effects was used during the relevant treatment period and its contribution cannot be distinguished.
- •The record is a duplicate treatment episode. For a patient with multiple eligible episodes, only the first eligible index hospitalization will be retained for the primary analysis.
研究组 & 干预措施
Yiqi Fumai Initiation Within 24 Hours
Patients who initiated Yiqi Fumai lyophilized injection within 24 hours after time zero during routine clinical care. Subsequent treatment duration, completion of a 10-day course, discontinuation, and crossover do not alter baseline strategy assignment in the primary intention-to-treat analogue.
干预措施: Yiqi Fumai Lyophilized Injection (Drug)
No Yiqi Fumai Initiation Within 24 Hours
Eligible patients who did not initiate Yiqi Fumai lyophilized injection within 24 hours after time zero during routine clinical care. Patients who initiated the drug later remain assigned to this baseline strategy in the primary intention-to-treat analogue and are recorded as treatment crossovers.
结局指标
主要结局
Total Direct Medical Cost From Time Zero Through the End of the Index Hospitalization
时间窗: From time zero to discharge from the index hospitalization or in-hospital death, whichever occurs first; an estimated average of 12 days.
Total direct medical cost incurred from time zero to discharge from the index hospitalization or in-hospital death, whichever occurs first, will be calculated from itemized medical records using quantity multiplied by unit price and standardized to 2026 Chinese yuan. Cost incurred from admission to time zero will be treated as a baseline covariate. Total cost for the complete index hospitalization will be evaluated in a sensitivity analysis. The estimated average is for registration planning and does not truncate observation; every index admission is followed to its actual endpoint.
Incidence of First Heart-Failure-Related Rehospitalization Within 90 Days
时间窗: From time zero through Day 90; qualifying rehospitalizations occur after discharge from the index hospitalization
The cumulative incidence of the first unplanned rehospitalization after index discharge for which heart failure is the primary diagnosis or there is clearly documented worsening of heart failure will be estimated through 90 days after time zero. Death before rehospitalization will be treated as a competing risk. Adjusted absolute risk, risk difference, relative effect, and 95% confidence intervals will be reported.
次要结局
- Incidence of First Heart-Failure-Related Rehospitalization Within 30 Days(From discharge from the index hospitalization through Day 30 after time zero)
- Incidence of Heart-Failure-Related Rehospitalization or All-Cause Death Within 90 Days(From time zero through Day 90)
- Incidence of All-Cause Death Within 90 Days(From time zero through Day 90)
- Incidence of Cardiovascular Death Within 90 Days(From time zero through Day 90)
- Length of the Index Hospitalization(From admission to discharge from the index hospitalization or in-hospital death, whichever occurs first; an estimated average of 12 days.)
- Proportion of Patients With ICU or CCU Use During the Index Hospitalization(From admission to discharge from the index hospitalization or in-hospital death, whichever occurs first; an estimated average of 12 days.)
- Duration of ICU or CCU Care During the Index Hospitalization(From admission to discharge from the index hospitalization or in-hospital death, whichever occurs first; an estimated average of 12 days.)
研究者
Lianxin Wang
Principal Investigator
China Academy of Chinese Medical Sciences