Polypills Approach for Multiple Cardiovascular Risk Factors (PACIF)

Polypills Approach for Multiple Cardiovascular Risk Factors (PACIF) : a Multicentre, Open-label, Randomized Controlled Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; Diabetes; Dyslipidemia
• Intervention / Treatment: Drug: Fixed-Dose Combination Strategy

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 8252
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China
      • Not yet recruiting
      • The First Affiliated Hospital of Henan University of Chinese Medicine
      • Contact: Xincan Liu; Phone Number: +86 13203825657; Email: Liuxincan103@163.com
  • Inner Mongolia
    • Chifeng, Inner Mongolia, China
      • Recruiting
      • Affiliated Hospital of Chifeng University
      • Contact: Xuchen Han; Phone Number: +86 15504766986; Email: hanxuchen2004@163.com
    • Tongliao, Inner Mongolia, China
      • Not yet recruiting
      • Tongliao People's Hospital
      • Contact: Kai Zheng; Phone Number: +86 15004963990; Email: udbmnm2012@163.com
  • Jiangsu
    • Kunshan, Jiangsu, China
      • Not yet recruiting
      • Kunshan Hospital of Chinese Medicine
      • Contact: Hengshan Shen; Phone Number: +86 13962637574; Email: 847658065@qq.com
    • Suzhou, Jiangsu, China
      • Not yet recruiting
      • The Second Affiliated Hospital of Soochow University
      • Contact: Jijun Shi; Phone Number: +86 18934593776; Email: shijijun2008@126.com
    • Suzhou, Jiangsu, China
      • Not yet recruiting
      • Suzhou Wujiang District Hospital of Traditional Chinese Medicine
      • Contact: Wangfeng Qian; Phone Number: +86 13771692578; Email: wfss873@sina.com
    • Suzhou, Jiangsu, China
      • Not yet recruiting
      • The Fifth People's Hospital of Wujiang District
      • Contact: Jun Li; Phone Number: +86 13913731272; Email: lijun19801005@163.com
    • Taizhou, Jiangsu, China
      • Not yet recruiting
      • Taixing Second People's Hospital
      • Contact: Ligong Ji; Phone Number: +86 13815979287; Email: 420643682@qq.com
  • Liaoning
    • Jinzhou, Liaoning, China
      • Recruiting
      • Central Hospital of Jinzhou
      • Contact: Shuai Jiang; Phone Number: +86 13897854774; Email: 13897854774@163.com
    • Panjin, Liaoning, China
      • Not yet recruiting
      • Panjin Central Hospital
      • Contact: Qiong Zhang; Phone Number: +86 15504272626; Email: yoner6789@163.com
    • Shenyang, Liaoning, China
      • Not yet recruiting
      • Shengjing Hospital of China Medical University
      • Contact: Anhua Wu; Phone Number: +86 18900925766; Email: ahwu@cmu.edu.cn
    • Shenyang, Liaoning, China, 110001
      • Recruiting
      • First Hospital of China Medical University
      • Contact: Guozhe Sun; Phone Number: +86 15040292137; Email: gzhsun66@163.com
    • Tieling, Liaoning, China
      • Recruiting
      • Tieling Central Hospital
      • Contact: Caixia Yang; Phone Number: +86 13704109696; Email: 2624603253@qq.com
    • Tieling, Liaoning, China
      • Recruiting
      • Tiemei General Hospital of Liaoning Health Industry Group
      • Contact: Geng Wang; Phone Number: +86 15542052188; Email: 15542052188@163.com
  • Shandong
    • Jinan, Shandong, China
      • Not yet recruiting
      • Shandong Provincial Hospital Affiliated to Shandong First Medical University
      • Contact: Xiaoming Zhou; Phone Number: +86 15168887283; Email: sdslyy@yeah.net

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Group; Usual care
Experimental: Experimental; Polypill intervention	Drug: Fixed-Dose Combination Strategy; Participants assigned to the intervention group will receive a fixed-dose combination strategy for the integrated control of blood pressure, lipid, and glucose. Eight prespecified fixed-dose formulations will be used, differing in antihypertensive intensity and rosuvastatin dose. All formulations will include olmesartan medoxomil/amlodipine, rosuvastatin, ezetimibe 10 mg, and dapagliflozin 10 mg, with indapamide 2.5 mg included in selected formulations. The olmesartan medoxomil/amlodipine dose will range from 5/1.25 mg to 20/5 mg, and the rosuvastatin dose will be either 5 mg or 10 mg. Treatment will be selected and adjusted among the prespecified fixed-dose formulations according to participants' blood pressure levels, treatment targets, tolerability, and safety. If the prespecified blood pressure, lipid, or glycemic targets are not achieved despite the highest fixed-dose regimen, additional open-label medications may be prescribed according to guideline recommendations.; Other Names: Polypill Strategy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
10-year CVD risk	Changes in 10-year CVD risk estimated by the PREVENT equations	12 months
Composite cardiovascular disease outcome	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	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
10-year ASCVD risk	Changes in 10-year ASCVD risk estimated by the PREVENT equations	12 months
10-year HF risk	Changes in 10-year HF risk estimated by the PREVENT equations	12 months
Medication adherence	Medication adherence assessed by participant self-report, pill count, or other prespecified adherence measures	12 months
Cost-effectiveness	Data on the costs of CVD risk assessment and management will be collected for both study groups. The cost-effectiveness analysis will estimate the incremental cost per unit reduction in estimated 10-year CVD risk in the intervention group compared with the control group.	12 months
Composite outcome of composite cardiovascular disease outcome or deaths	Record the occurrence of composite outcome of composite cardiovascular disease outcome or deaths	36 months
Macrovascular outcome	Record the occurrence of any of the following: stroke, myocardial infarction, heart failure requiring hospitalization or treatment, aortic dissection, any cardiovascular revascularization procedures, or cardiovascular death	36 months
Major coronary artery diseases	Record the occurrence of any of the following: myocardial infarction, revascularization of coronary arteries, or deaths due to coronary artery diseases	36 months
New-onset chronic kidney disease or progression of chronic kidney disease	Record the occurrence of new-onset chronic kidney disease or progression of chronic kidney disease	36 months
Medication adherence	Medication adherence assessed by participant self-report, pill count, or other prespecified adherence measures	36 months
Health related quality of life	Health-related quality of life will be assessed by the Five-Level Version of the EQ-5D (EQ-5D-5L). In this questionnaire, 5 dimensions are measured in 5 items: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. A 5-point Likert scale ranging from "no problems" to "extreme problems" is used for every dimension, with higher scores reflecting more problems in a dimension. A VAS ranging from 0 to 100 (0 = "The best health you can imagine" to 100 = "The worst health you can imagine") is applied as well, with higher scores indicating a better health state as perceived by the patient.	36 months
Cost-effectiveness	Cost-effectiveness assessed by the incremental cost-effectiveness ratio, expressed as the incremental cost per quality-adjusted life-year gained. Quality-adjusted life-years will be estimated from health utilities derived using the EQ-5D-5L questionnaire.	36 months
Major secondary endpoint: All-cause dementia	Record the occurrence of all-cause dementia	36 months
Hierarchical composite of all-cause mortality, nonfatal cardiovascular events, and improvement in 10-year cardiovascular disease risk estimated by the PREVENT equations	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	The proportions of participants achieving the prespecified targets for blood pressure (systolic blood pressure <130 mmHg and diastolic blood pressure <80 mmHg), LDL-C (<1.8 mmol/L), and HbA1c (<7.0%), individually and jointly	12 months
Blood pressure, LDL-C, and HbA1c	Changes in systolic and diastolic 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	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	The proportions of participants achieving the prespecified targets for blood pressure (systolic blood pressure <130 mmHg and diastolic blood pressure <80 mmHg), LDL-C (<1.8 mmol/L), and HbA1c (<7.0%), individually and jointly	36 months
Blood pressure, LDL-C, and HbA1c	Changes in systolic and diastolic blood pressure, LDL-C, and HbA1c	36 months
Myocardial infarction	Record the occurrence of myocardial infarction	36 months
Stroke	Record the occurrence of stroke	36 months
Ischemic stroke	Record the occurrence of ischemic stroke	36 months
Hemorrhagic stoke	Record the occurrence of hemorrhagic stroke	36 months
Heart failure requiring hospitalization or treatment	Record the occurrence of heart failure requiring hospitalization or treatment	36 months
Coronary revascularization	Record the occurrence of coronary revascularization	36 months
Cardiovascular disease death	Record the occurrence of cardiovascular disease death	36 months
All-cause death	Record the occurrence of all-cause death	36 months
Microvascular outcomes	Record the occurrence of microvascular complications (e.g., diabetic kidney disease and diabetic peripheral neuropathy)	36 months
Mild cognitive impairment	Record the occurrence of mild cognitive impairment	36 months
Composite outcome of dementia and mild cognitive impairment	Record the occurrence of the composite outcome of dementia and mild cognitive impairment	36 months
Composite outcome of dementia and all-cause death	Record the occurrence of the composite outcome of dementia and all-cause death	36 months

Collaborators and Investigators

• Sponsor: China Medical University, China

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): March 1, 2030

Study Registration Dates

• First Submitted: June 21, 2026
• First Submitted That Met QC Criteria: June 25, 2026
• First Posted (Actual): July 1, 2026

Study Record Updates

• Last Update Posted (Actual): September 16, 2026
• Last Update Submitted That Met QC Criteria: September 12, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Diabetes; Dyslipidemia; Cardiovascular Diseases; Hypertension; Randomized controlled trial; Cardiovascular disease risk; Cognitive function; Polypill
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Lipid Metabolism Disorders; Nutritional and Metabolic Diseases; Hypertension; Cardiovascular Diseases; Diabetes Mellitus; Dyslipidemias
• Other Study ID Numbers: CMU-polypill

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No