Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients

Study Overview
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Brief Summary
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The Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) is a 2-arm, multi-center, prospective, randomized, open-labeled, blinded-endpoint trial. The purpose of this trial is to test whether a treatment program aimed at reducing systolic blood pressure (SBP) to a lower goal (<130 mmHg, intensive treatment) than currently recommended (<150 mmHg, standard treatment) will reduce CVD risk among persons between 60-80 years of old. Furthermore, this trial will also examine the effect of blood pressure APP management strategy via WeChat network on medication compliance, blood pressure control and CVD benefits.

Detailed Description
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Hypertension is highly prevalent in the adult population in China, and its burden is rapidly increasing among persons older than 60 years of age. Elevated blood pressure (BP) is an important public health concern which contributes to several adverse health outcomes, especially coronary heart disease, stroke, heart failure, chronic kidney disease, and decline in cognitive function. Clinical trials have shown that a lower systolic blood pressure goal will lead to greater reduction in cardiovascular disease (CVD) incidence, but the effect of intensive treatment of systolic blood pressure below 120 mm Hg in reducing of CVD risk has long been debated. In particularly, among the elderly hypertensive patients aged 60 years or older, the most appropriate targets for blood pressure lowering to reduce cardiovascular events still remain uncertain. The STEP trial will randomize about 8000 participants aged between 60 and 80 years with SBP≥140 mm Hg and <190 mm Hg, and without a history of atherothrombotic or hemorrhagic stroke. Target SBP goals are 110-130 vs 130-150 mm Hg, respectively. The purpose of the STEP trial is to test whether a treatment program aimed at reducing systolic blood pressure (SBP) to a lower goal (<130 mmHg, intensive treatment) than currently recommended (<150 mmHg, standard treatment) will reduce CVD risk among hypertensive patients between 60-80 years. Participants will be recruited at approximately 40 clinic centers in China within approximately a 1-year period, and will be followed for 4 years. Furthermore, this trial will also examine the effect of blood pressure APP management strategy via WeChat network on medication compliance, blood pressure control and CVD benefits.

Official Title
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Strategy of Systolic Blood Pressure Intervention in the Elderly Hypertensive Patients: A Prospective Randomized Open-Label Blinded-Endpoint Trial

Conditions
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Primary Hypertension

Intervention / Treatment
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* Drug: Intensive BP control
* Drug: Standard BP control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Systolic BP between 140-190 mm Hg in the three screening visits or currently under anti-hypertension treatment； An age of 60 - 80 years old； Signed the written informed consent. Exclusion Criteria: Systolic BP≥190 mm Hg, or diastolic BP <60 mm Hg; Known secondary cause of hypertension; History of large atherosclerotic cerebral infarction or hemorrhagic stroke (not lacunar infarction and transient ischemic attack [TIA]); Hospitalization for myocardial infarction or unstable angina within the previous 6 months; Coronary revascularization (PCI or CABG) within the previous 12 months; Planned to perform coronary revascularization (PCI or CABG) in the future 12 months; History of sustained atrial fibrillation or Ventricular arrhythmias at entry influencing the measurement of electronic blood pressure； NYHA class III-IV heart failure at entry or hospitalization for exacerbation of chronic heart failure within the previous 6 months; Severe valvular disease or valvular disease likely to require surgery or percutaneous valve replacement during the trial; Dilated or hypertrophic cardiomyopathy, rheumatic heart disease, or congenital heart disease; Uncontrolled diabetes (serum fasting glucose ≥200 mg/dl [11.1 mmol/L], HbA1>8%); Lab tests indicating abnormal liver or kidney function (ALT more than 3 times the upper limit of normal value, or end stage renal disease (ESRD) on dialysis, or estimated glomerular filtration rate (eGFR) <30 mL/min, or serum creatine >2.5 mg/dl [>221 umol/L]; Severe somatic disease such as cancer; Severe cognitive impairment or mental disorders; Participating in other clinical trials.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intensive BP control<br>SBP within 110 - <130 mm Hg. Participants randomized into the Intensive BP control arm will have a goal of SBP 110 - <130 mm Hg. | Drug: Intensive BP control<br>* For all participants, Olmesartan Medoxomil tablets or Amlodipine Besylate tablets will be used as an initial therapy. Other drugs, including hydrochlorothiazide and β-blockers, are allowed, in order to achieve the SBP target. If the target BP level is not achieved during the Follow-up periods, adjustment of drug type and dosage will be carried out according to procedures defined in the protocol.<br>* Other names: Lower target for reducing SBP;|
| Active Comparator: Standard BP control<br>SBP within 130 - <150 mm Hg. Participants randomized into the Intensive BP control arm will have a goal of SBP 130 - <150 mm Hg. | Drug: Standard BP control<br>* For all participants, Olmesartan Medoxomil tablets or Amlodipine Besylate tablets will be used as an initial therapy. Other drugs, including hydrochlorothiazide and β-blockers, are allowed, in order to achieve the SBP target. If the target BP level is not achieved during the Follow-up periods, adjustment of drug type and dosage will be carried out according to procedures defined in the protocol.<br>* Other names: Standard target for reducing SBP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary composite outcome | A composite end-point comprised of acute coronary syndrome (myocardial infarction and hospitalization for unstable angina), first occurrence of symptomatic stroke ( ischemic or hemorrhagic stroke), hospitalization for decompensated heart failure, coronary revascularization (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG]), atrial fibrillation, and death from cardiovascular causes. | 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite of major adverse cardiac events (primary outcome without stroke) | Composite of major adverse cardiac events comprised of acute coronary syndrome (myocardial infarction and hospitalization for unstable angina), hospitalization for decompensated heart failure, coronary revascularization (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG]), atrial fibrillation, and death from cardiovascular causes. | 4 years | 
| First occurrence of symptomatic stroke ( ischemic or hemorrhagic) | Stroke is defined as a rapid onset of focal (or global) disturbance of cerebral function lasting more than 24 hours (except interrupted by surgery or death) without resolution of symptoms according to the World Health Organization. The diagnosis of stroke is confirmed by strict neurological examination, computed tomography (CT), or magnetic resonance imaging (MRI), and stroke subtypes are classified including ischemic or hemorrhagic, fatal or not fatal. | 4 years | 
| Acute coronary syndrome | Acute coronary syndrome includes myocardial infarction and hospitalization for unstable angina. The diagnosis of MI is based on the following criteria: (1) Patient has cardiac signs and symptoms, such as retrosternal pain last for at least 30 minutes, and not relieve to nitroglycerine during the attack; (2) Electrocardiographic abnormal findings of MI are observed; (3) Biochemical markers of cardiac damage are present. The diagnosis of unstable angina requires hospitalization for evaluation. The clinical presentation of unstable angina includes: (1) prolonged (>20 min) angina pain at rest; (2) new onset angina; (3) post-MI angina; (4) recent destabilization of previously stable angina with at least Canadian Cardiovascular Society Class III angina characteristics. | 4 years | 
| Hospitalization for acute decompensated heart failure | Diagnosis of acute decompensated heart failure requires a hospitalization or emergency department visit which provides an infusion therapy for clinical signs and symptoms consistent with cardiac decompensation or inadequate cardiac pump function, such as increasing or new onset shortness of breath, peripheral edema, paroxysmal dyspnea, orthopnea, or hypoxia. | 4 years | 
| coronary revascularization (percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG]) | Patients are treated with coronary revascularization by either PCI or CABG due to acute coronary syndromes (ACS) and stable ischemic heart disease (SIHD). | 4 years | 
| Atrial fibrillation | Diagnosis of AF requires rhythm evidence of an ECG showing the typical pattern including absolutely irregular RR intervals and no discernible, distinct P waves. | 4 years | 
| Cardiovascular death | Cardiovascular death includes fatal coronary heart disease, fatal stroke, death from heart failure, and sudden cardiac death. | 4 years | 
| All-cause death | All-cause death includes death due to any reasons during the trial. Evidence for death includes death certificates from hospitals or reports of home visit from investigators. | 4 years | 
| First occurrence of diabetes mellitus | Diagnosis of incident diabetes mellitus includes the following criteria: (1) Fasting plasma glucose ≥ 126 mg/dl (≥ 7.0 mmol/dl); or (2) Oral glucose tolerance test 2-hour glucose in venous plasma ≥ 200 mg/dl (≥ 11.1 mmol/l); or (3) In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥ 200 mg/dl (≥ 11.1 mmol/l); or (4) Glycosylated hemoglobin (HbA1c) ≥ 6.5% (48 mmol/mol). | 4 years | 
| Decline in cognitive function | Decline in cognitive function includes sensory disturbance, memory disorders and thinking disorders, which is assessed by mini-mental state examination (MMSE) | 4 years | 
| Decline in renal function or development of end stage renal disease (ESRD) | Decline in renal function is assessed by any of the following: (1) For patients with chronic kidney disease (eGFR <60 ml per minute per 1.73 m2) at baseline, the renal outcome was a composite of a decrease in the eGFR of 50% or more (confirmed by a subsequent laboratory test) or the development of ESRD requiring long-term dialysis or kidney transplantation; or (2) For participants without chronic kidney disease at baseline, the renal outcome was defined by a decrease in the eGFR of 30% or more to a value of less than 60 ml per minute per 1.73 m2. | 4 years | 
| Major artery stiffness | Major artery stiffness are assessed by a composite of decrease in the ankle brachial index [ABI], brachial-ankle pulse wave velocity(baPWV), or brachial artery flow-mediated dilation [FMD]. ABI and baPWV,well-established non-invasive techniques for evaluating obstruction and stiffness of peripheral artery respectively, are considered for the purposes of cardiovascular risk assessment. ABI is the ratio of the average systolic blood pressure measured in brachial/ankle, and an ABI between and including 0.9 and 1.2 is considered normal, while a lesser than 0.9 indicates arterial disease. The unit measure of baPWV value is cm per second. FMD serves as an index of nitric oxide (NO)-mediated endothelium-dependent vasodilator function in humans and is regarded as a surrogate marker of cardiovascular disease. | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blood pressure control