Clinical trial NCT03808311: Blood Pressure Control Target in Diabetes
Official title: Blood Pressure Control Target in Diabetes (BPROAD): a Multicenter, Open-label, Parallel-group, Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Blood Pressure Control Target in Diabetes
Lead sponsor: Shanghai Jiao Tong University School of Medicine
Sponsor class: OTHER
First posted: 2019-01-17
Enrollment: 12821
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, open-label, parallel-group, randomized controlled trial that will be conducted across mainland China. This trial will test the primary hypothesis of whether an intensive treatment strategy (a systolic blood pressure target of \<120 mmHg) is more effective than a standard treatment strategy (a systolic blood pressure target of \<140 mmHg) in reducing the risk of major cardiovascular disease (non-fatal stroke, non-fatal myocardial infarction, treated or hospitalized heart failure, and cardiovascular deaths) over a follow-up period of up to 5 years among patients with a history of diabetes and elevated systolic blood pressure. The secondary hypotheses are to compare the intensive blood pressure treatment strategy with the standard treatment strategy on cognitive function, individual components of the primary hypothesis, all-cause mortality, kidney outcomes, quality of life, and injurious falls, et al.

Detailed description: 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:

1. 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;
2. 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;
3. 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;
4. Obtain clinical data on study outcomes for up to 60 months of follow-up among all trial participants;
5. Perform strict quality control procedures for intervention and data collection;
6. Conduct data analysis according to the intention-to-treat principle; and
7. 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.

Eligibility criteria: Inclusion Criteria:

1. Men and women aged ≥50 years;
2. 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);
3. 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;
4. 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:

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

Primary outcomes:
measure: Major cardiovascular events
timeFrame: 5 years
Secondary outcomes:
measure: A composite of the primary outcome and all-cause mortality
timeFrame: 5 years
measure: Macrovascular outcome
timeFrame: 5 years
measure: Major coronary artery diseases
timeFrame: 5 years
measure: Total MI
timeFrame: 5 years
measure: Total stroke
timeFrame: 5 years
measure: Ischemic stroke
timeFrame: 5 years
measure: Hemorrhagic stoke
timeFrame: 5 years
measure: Heart failure
timeFrame: 5 years
measure: Cardiovascular death
timeFrame: 5 years
measure: Total mortality
timeFrame: 5 years
measure: Cognitive function
timeFrame: 5 years
measure: Health related quality of life
timeFrame: 5 years
measure: Kidney outcomes
timeFrame: 5 years
Other outcomes:
measure: All cardiovascular revascularization procedures
timeFrame: 5 years
measure: Hospitalized unstable angina
timeFrame: 5 years
measure: Retinopathy
timeFrame: 5 years
measure: Transient ischemic attack (TIA)
timeFrame: 5 years
measure: Left ventricular hypertrophy (LVH)
timeFrame: 5 years
measure: Atrial fibrillation or flutter
timeFrame: 5 years
measure: All cancers
timeFrame: 5 years
measure: Cost-effectiveness
timeFrame: 5 years
Locations:
city: Shanghai
country: China
facility: Ruijin hospital, Shanghai Jiaotong University School of Medicine
state: Shanghai
Study officials:
affiliation: Shanghai Jiao Tong University School of Medicine
name: Guang Ning, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Saiz LC, Gorricho J, Garjon J, Celaya MC, Erviti J, Leache L. Blood pressure targets for the treatment of people with hypertension and cardiovascular disease. Cochrane Database Syst Rev. 2022 Nov 18;11(11):CD010315. doi: 10.1002/14651858.CD010315.pub5.
citation: Saiz LC, Gorricho J, Garjon J, Celaya MC, Erviti J, Leache L. Blood pressure targets for the treatment of people with hypertension and cardiovascular disease. Cochrane Database Syst Rev. 2020 Sep 9;9(9):CD010315. doi: 10.1002/14651858.CD010315.pub4.