Blood Pressure Control Target in Diabetes

The trial will recruit 12,702 patients from approximately 150 hospitals within the China Diabetes Clinical Research Network. Eligible criteria include men and women aged ≥50 years; type 2 diabetes mellitus; elevated systolic blood pressure; and a history of clinical cardiovascular disease or increased risk for cardiovascular disease. Main exclusion criteria include known secondary cause of hypertension, symptomatic heart failure, end-stage renal disease, and other serious illness. The proposed trial has 90% statistical power to detect a 20% reduction (hazard ratio of 0.80) in major cardiovascular disease between intensive and standard treatment groups at a 2-sided significance level of 0.05.

To achieve the proposed study objectives, the following specific aims will be accomplished:

• Recruit 12,702 study participants who meet the eligibility criteria and randomly assign 6,351 to the intensive blood pressure treatment and 6,351 to the standard blood pressure treatment groups;
• Achieve and maintain two-level targets of systolic blood pressure (<120 mmHg vs. <140 mmHg) with a mean systolic blood pressure difference of ≥15 mmHg;
• Employ a study-wide strategy to encourage standard of care for all participants for the treatment of type 2 diabetes and dyslipidemia other than blood pressure;
• Obtain clinical data on study outcomes for up to 60 months of follow-up among all trial participants;
• Perform strict quality control procedures for intervention and data collection;
• Conduct data analysis according to the intention-to-treat principle; and
• Disseminate the study findings to influence clinical practice and clinical guidelines.

Findings from this trial will provide evidence as to whether intensive blood pressure management to achieve a systolic blood pressure target of <120 mmHg has additional benefits over standard management of systolic blood pressure <140 mmHg. These findings will help in the development of clinical guidelines for blood pressure management among patients with type 2 diabetes and will have important clinical impact.

Inclusion criteria

• Men and women aged ≥50 years;
• Diabetes defined as:

• A self-reported previous diagnosis by health care professionals and taking anti-diabetic medications;
• Fasting plasma glucose level of ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 hours;
• 2-hour plasma glucose level of ≥200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test. The test should be performed using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water; or
• HbA1c concentration of ≥6.5% (48 mmol/mol);
• Systolic blood pressure

-≥140 mmHg on 0 medication;

• 130-180 mmHg on 1 medication;
• 130-170 mmHg on up to 2 medications;
• 130-160 mmHg on up to 3 medications; or
• 130-150 mmHg on up to 4 medications;
• Increased risk of cardiovascular disease (one or more of the following):

• Previous history of clinical CVD (≥ 3 months)
• Subclinical CVD within 3 years
• 2 or more CVD risk factors
• Estimated glomerular filtration rate (eGFR) 30-59 ml/min/1.73 m2

Exclusion criteria

• History consistent with type 1 diabetes
• Known secondary cause of hypertension
• One minute standing systolic BP <110 mmHg
• Arm circumference too large to allow accurate blood pressure measurement with available devices
• Cardiovascular event or procedure or hospitalization for unstable angina within the past 3 months
• Symptomatic heart failure within the past 6 months or left ventricular ejection fraction (by any method) <35% within the past 6 months
• ALT or AST levels more than twice the upper limit of the normal range or active liver diseases
• Dialysis, kidney transplantation, eGFR <30 ml/min/1.73 m2, or serum creatinine >2.0 mg/dl
• Proteinuria
• Previous diagnosis of polycystic kidney disease or glomerulonephritis
• A medical condition likely to limit survival to less than 5 years
• Any factors judged by the clinic team to be likely to limit adherence to interventions
• Failure to obtain informed consent from participant
• Currently participating in another intervention study
• Currently living with another BPROAD participant
• Pregnancy, currently trying to become pregnant, or of child-bearing potential and not using birth control