Polypills Approach for Multiple Cardiovascular Risk Factors (PACIF) : a Multicentre, Open-label, Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 8,252
- 试验地点
- 27
- 主要终点
- 10-year CVD risk
研究概览
简要总结
The Polypill Approach for Multiple Cardiovascular Risk Factors (PACIF) trial is a multicenter randomized controlled trial that will test the effectiveness and safety of a fixed-dose combination strategy for the integrated management of hypertension, dyslipidemia, and type 2 diabetes among adults aged 50 to 75 years without prior cardiovascular disease in China. The trial will evaluate whether a fixed-dose combination strategy improves the 10-year cardiovascular disease risk estimated using the PREVENT equations at Phase 1. Participants will be further followed to determine whether the fixed-dose combination strategy reduces major cardiovascular events and improves cognitive outcomes compared with usual care at Phase 2.
详细描述
The overall objective of the PACIF Trial is to test a fixed-dose combination strategy for the integrated management of hypertension, dyslipidemia, and diabetes. This multicenter randomized controlled trial will evaluate whether a polypill-based approach, compared with usual care, improves cardiovascular risk factor control and reduces cardiovascular disease events among adults with multiple cardiovascular risk factors but without prior cardiovascular disease. The trial will recruit an estimated 8,252 participants aged 50 to <75 years who have hypertension, dyslipidemia, and type 2 diabetes. Participants will be randomly assigned to receive either a fixed-dose combination strategy or usual care.
In the intervention group, the study medication regimen will consist of eight prespecified fixed-dose formulations combining blood pressure-lowering, lipid-lowering, and glucose-lowering therapies. These formulations include olmesartan medoxomil/amlodipine, rosuvastatin, ezetimibe, and dapagliflozin, with indapamide included in selected formulations. Treatment will be adjusted among the prespecified fixed-dose formulations according to participants' blood pressure levels, treatment targets, tolerability, and safety. Additional open-label medications may be used according to guideline recommendations and clinical judgment if the prespecified treatment targets are not achieved with the fixed-dose combination strategy. Treatment targets are defined as blood pressure <130/80 mmHg, LDL cholesterol <1.8 mmol/L, and HbA1c <7.0%.
The primary outcome at Phase 1 is the ACC/AHA 10-year cardiovascular disease risk estimated by the PREVENT equations. In addition, changes in PREVENT-estimated 10-year ASCVD and heart failure risk, the proportions of participants achieving the prespecified blood pressure, lipid, and glycemic targets, and changes in individual cardiovascular risk factors will also be evaluated.
The primary outcome at Phase 2 is a composite cardiovascular disease outcome including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure requiring hospitalization or treatment, and coronary revascularization. Cognitive outcomes will also be assessed, with incident all-cause dementia prespecified as a major secondary outcome.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Outcome Assessment Committee members will be blinded to outcome assignment.
入排标准
- 年龄范围
- 50 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men or women
- •Age ≥50 years and <75 years
- •Systolic blood pressure ≥130 mmHg
- •LDL-C ≥1.8 mmol/L (70 mg/dL)
- •Type 2 diabetes with HbA1c ≥6.5% and <12%
- •Willing to participate and able to sign informed consent
排除标准
- •Known secondary cause of hypertension
- •Type 1 diabetes
- •Pancreatic insufficiency or diabetes secondary to pancreatitis
- •Triglycerides ≥5.65 mmol/L (500 mg/dL)
- •History of myocardial infarction, stroke, or heart failure
- •History of coronary, cerebrovascular, or peripheral arterial revascularization
- •Abnormal kidney function, defined as estimated glomerular filtration rate <30 mL/min/1.73 m² or dialysis
- •Abnormal liver function, defined as alanine aminotransferase or aspartate aminotransferase >3 times the upper limit of normal
- •Abnormal serum potassium, defined as serum potassium >5.5 mmol/L or <3.5 mmol/L
- •Contraindication to any of the components of the polypill
- •Currently living with another PACIF participant
- •Pregnancy, currently trying to become pregnant, or of child-bearing potential and not using birth control
- •Clinical diagnosis of dementia or treatment with medications for dementia
- •History of malignancy
- •Life expectancy <3 years
- •Currently participating in another intervention study
- •Any factors judged by the clinic team to be likely to limit adherence to interventions
研究组 & 干预措施
Experimental
Polypill intervention
干预措施: Fixed-Dose Combination Strategy (Drug)
Control Group
Usual care
结局指标
主要结局
10-year CVD risk
时间窗: 12 months
Changes in 10-year CVD risk estimated by the PREVENT equations
Composite cardiovascular disease outcome
时间窗: 36 months
Record the occurrence of the composite cardiovascular disease outcome, including cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure requiring hospitalization or treatment, and coronary revascularization
次要结局
- The proportion of patients achieved blood pressure target(12 months)
- 10-year ASCVD risk(12 months)
- 10-year HF risk(12 months)
- The proportion of patients achieved LDL-C target(12 months)
- The proportion of patients achieved HbA1c target(12 months)
- The proportion of patients achieved all three targets (blood pressure, LDL-C, and HbA1c)(12 months)
- Blood pressure(12 months)
- LDL-C(12 months)
- HbA1c(12 months)
- Medication adherence(12 months)
- Cost-effectiveness(12 months)
- The proportion of patients achieved blood pressure target(36 months)
- The proportion of patients achieved LDL-C target(36 months)
- The proportion of patients achieved HbA1c target(36 months)
- The proportion of patients achieved all three targets (blood pressure, LDL-C, and HbA1c)(36 months)
- Blood pressure(36 months)
- LDL-C(36 months)
- HbA1c(36 months)
- Composite outcome of composite cardiovascular disease outcome or deaths(36 months)
- Macrovascular outcome(36 months)
- Major coronary artery diseases(36 months)
- Aortic dissection(36 months)
- Cancer(36 months)
- New-onset chronic kidney disease or progression of chronic kidney disease(36 months)
- Medication adherence(36 months)
- Health related quality of life(36 months)
- Cost-effectiveness(36 months)
- Major secondary endpoint: All-cause dementia(36 months)
- Myocardial infarction(36 months)
- Stroke(36 months)
- Ischemic stroke(36 months)
- Hemorrhagic stoke(36 months)
- Heart failure requiring hospitalization or treatment(36 months)
- Cardiovascular disease death(36 months)
- All-cause death(36 months)
- Mild cognitive impairment(36 months)
- Composite outcome of dementia and mild cognitive impairment(36 months)
- Hierarchical composite of all-cause mortality, nonfatal cardiovascular events, and improvement in 10-year cardiovascular disease risk estimated by the PREVENT equations(12 months)
- The proportions of participants achieving the prespecified blood pressure, LDL-C, and HbA1c targets, individually and jointly(12 months)
- Blood pressure, LDL-C, and HbA1c(12 months)
- Hierarchical composite of all-cause mortality, nonfatal cardiovascular events, and improvement in 10-year cardiovascular disease risk estimated by the PREVENT equations(36 months)
- The proportions of participants achieving the prespecified blood pressure, LDL-C, and HbA1c targets, individually and jointly(36 months)
- Blood pressure, LDL-C, and HbA1c(36 months)
- Coronary revascularization(36 months)
- Microvascular outcomes(36 months)
- Composite outcome of dementia and all-cause death(36 months)
研究者
Guozhe Sun
Deputy Chief of the Department of Cardiology, First Hospital of China Medical University
First Hospital of China Medical University