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 integrated management of hypertension, dyslipidemia, and diabetes among adults aged 50 to 75 years in China. The trial will evaluate whether a simplified regimen combining blood pressure-lowering, lipid-lowering, and glucose-lowering therapy improves the 10-year cardiovascular disease risk score at phase 1. Participants will be followed to determine whether the fixed-dose combination strategy reduces major cardiovascular events and cognitive function compared with usual care at phase 2.

Study Overview

• Status: Not yet 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. The trial will recruit an estimated 8,252 participants aged 50 to 75 years who have hypertension, dyslipidemia, and 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 six fixed-dose formulations, including three antihypertensive formulations, two lipid-lowering formulations, and one glucose-lowering formulation. The antihypertensive component will be titrated using prespecified dose combinations, including olmesartan medoxomil/amlodipine and indapamide, until the blood pressure target is achieved. Lipid-lowering therapy will be initiated with rosuvastatin plus ezetimibe, with dose reduction of the rosuvastatin component in participants who are intolerant to the initial statin dose. Glucose-lowering therapy will include dapagliflozin as the prespecified study medication. Treatment targets are defined as systolic blood pressure <130 mmHg and diastolic blood pressure <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, the proportions of participants achieving the prespecified blood pressure, lipid, and glycemic targets will also be evaluated. The primary outcome at phase 2 is composite cardiovascular disease events, including myocardial infarction, stroke, heart failure requiring hospitalization or treatment, or cardiovascular death. Cognitive function will also be assessed, with incident dementia prespecified as a major secondary endpoint.

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

Contacts and Locations

Study Locations

• China
  • Inner Mongolia
    • Chifeng, Inner Mongolia, China
      • Affiliated Hospital of Chifeng University
  • Jiangsu
    • Kunshan, Jiangsu, China
      • Kunshan Hospital of Chinese Medicine
    • Suzhou, Jiangsu, China
      • The Second Affiliated Hospital of Soochow University
    • Suzhou, Jiangsu, China
      • Suzhou Wujiang District Hospital of Traditional Chinese Medicine
    • Suzhou, Jiangsu, China
      • The Fifth People's Hospital of Wujiang District
    • Taizhou, Jiangsu, China
      • Taixing Second People's Hospital
  • Liaoning
    • Jinzhou, Liaoning, China
      • Central Hospital of Jinzhou
    • Panjin, Liaoning, China
      • Panjin Central Hospital
    • Shenyang, Liaoning, China
      • Shengjing Hospital of China Medical University
    • Shenyang, Liaoning, China
      • First Hospital of China Medical University
    • Tieling, Liaoning, China
      • Tiemei General Hospital of Liaoning Health Industry Group
  • Shandong
    • Jinan, Shandong, China
      • Shandong Provincial Hospital Affiliated to Shandong First Medical University

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
• Hypertension, defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg among participants not currently taking antihypertensive medication, or systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg among participants currently taking any antihypertensive medication
• Dyslipidemia, defined as 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 coronary, carotid, or cerebrovascular revascularization within the previous 12 months
• History of myocardial infarction or stroke within the previous 6 months
• NYHA class III-IV heart failure at entry or hospitalization for exacerbation of chronic heart failure within the previous 6 months
• 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 integrated control of blood pressure, lipid, and glucose. Six predefined medication regimens will be used, differing in antihypertensive intensity and rosuvastatin dose. The antihypertensive component will consist of olmesartan medoxomil/amlodipine at 10/2.5 mg or 20/5 mg, with indapamide 2.5 mg added if needed, and will be titrated toward a blood pressure target of <130/80 mm Hg according to prespecified protocol rules. The lipid-lowering component will be initiated with rosuvastatin 10 mg plus ezetimibe 10 mg. If suspected statin-associated adverse effects or statin intolerance occur, the rosuvastatin dose may be reduced from 10 mg to 5 mg according to prespecified protocol rules. The glucose-lowering component will consist of dapagliflozin at a fixed dose of 10 mg. Treatment will be selected and adjusted according to treatment targets, tolerability, and safety.; 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 newly diagnosed composite cardiovascular disease	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major secondary endpoint: All-cause dementia	Record all-cause dementia	36 months
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
The proportion of patients achieved blood pressure target	The proportion of patients achieved blood pressure target (systolic blood pressure <130 mmHg and diastolic blood pressure <80 mmHg)	12 months
The proportion of patients achieved LDL-C target	The proportion of patients achieved LDL-C target (LDL-C <1.8 mmol/L)	12 months
The proportion of patients achieved HbA1c target	The proportion of patients achieved HbA1c target (HbA1c <7.0%)	12 months
The proportion of patients achieved all three targets (blood pressure, LDL-C, and HbA1c)	The proportion of patients achieved all three targets (systolic blood pressure <130 mmHg and diastolic blood pressure <80 mmHg, LDL-C <1.8 mmol/L, and HbA1c <7.0%)	12 months
Blood pressure	Changes in systolic and diastolic blood pressure	12 months
LDL-C	Changes in LDL-C	12 months
HbA1c	Changes in HbA1c	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
The proportion of patients achieved blood pressure target	The proportion of patients achieved blood pressure target (systolic blood pressure <130 mmHg and diastolic blood pressure <80 mmHg)	36 months
The proportion of patients achieved LDL-C target	The proportion of patients achieved LDL-C target (LDL-C <1.8 mmol/L)	36 months
The proportion of patients achieved HbA1c target	The proportion of patients achieved HbA1c target (HbA1c <7.0%)	36 months
The proportion of patients achieved all three targets (blood pressure, LDL-C, and HbA1c)	The proportion of patients achieved all three targets (systolic blood pressure <130 mmHg and diastolic blood pressure <80 mmHg, LDL-C <1.8 mmol/L, and HbA1c <7.0%)	36 months
Blood pressure	Changes in systolic and diastolic blood pressure	36 months
LDL-C	Changes in LDL-C	36 months
HbA1c	Changes in HbA1c	36 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
Myocardial infarction	Number of newly diagnosed myocardial infarction	36 months
Stroke	Number of newly diagnosed stroke	36 months
Ischemic stroke	Number of newly diagnosed ischemic stroke	36 months
Hemorrhagic stoke	Number of newly diagnosed hemorrhagic stroke	36 months
Heart failure requiring hospitalization or treatment	Number of patients with newly diagnosed heart failure requiring hospitalization or treatment	36 months
Cardiovascular disease death	Number of cardiovascular disease death	36 months
All-cause death	Number of all-cause death	36 months
Aortic dissection	Number of newly diagnosed aortic dissection	36 months
Cancer	Number of newly diagnosed cancer	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
Mild cognitive impairment	Record mild cognitive impairment	36 months
Composite outcome of dementia and mild cognitive impairment	Record the composite outcome of dementia and mild cognitive impairment	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

Collaborators and Investigators

• Sponsor: China Medical University, China

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 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): July 1, 2026
• Last Update Submitted That Met QC Criteria: June 25, 2026
• Last Verified: June 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