Polypills Approach for Multiple Cardiovascular Risk Factors

Official title

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

Overview

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.

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.

Interventions

• 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 pres

Primary outcome measures

• 10-year CVD risk [Time frame: 12 months]
• Composite cardiovascular disease outcome [Time frame: 36 months]

Secondary outcome measures (12)

• Major secondary endpoint: All-cause dementia [Time frame: 36 months]
• 10-year ASCVD risk [Time frame: 12 months]
• 10-year HF risk [Time frame: 12 months]
• The proportion of patients achieved blood pressure target [Time frame: 12 months]
• The proportion of patients achieved LDL-C target [Time frame: 12 months]
• The proportion of patients achieved HbA1c target [Time frame: 12 months]
• The proportion of patients achieved all three targets (blood pressure, LDL-C, and HbA1c) [Time frame: 12 months]
• Blood pressure [Time frame: 12 months]
• LDL-C [Time frame: 12 months]
• HbA1c [Time frame: 12 months]
• Medication adherence [Time frame: 12 months]
• Cost-effectiveness [Time frame: 12 months]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 12 centers

• Affiliated Hospital of Chifeng University — Chifeng
• Kunshan Hospital of Chinese Medicine — Kunshan
• Suzhou Wujiang District Hospital of Traditional Chinese Medicine — Suzhou
• The Fifth People's Hospital of Wujiang District — Suzhou
• The Second Affiliated Hospital of Soochow University — Suzhou
• Taixing Second People's Hospital — Taizhou
• Central Hospital of Jinzhou — Jinzhou
• Panjin Central Hospital — Panjin
• … and 4 more centers

Identifiers

NCT: NCT07679828 · CMU-polypill

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗