Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients

Primary Hypertension Clinical Trial

— STEP  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03015311
• Other study ID #: 2016CXGC07
• Secondary ID: 2016-I2M-1-006
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 15, 2017
• Est. completion date: December 31, 2021

Study information

• Verified date: July 2021
• Source: Chinese Academy of Medical Sciences, Fuwai Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 8000
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Systolic BP between 140-190 mm Hg in the three screening visits or currently under anti-hypertension treatment;

2. An age of 60 - 80 years old;

3. Signed the written informed consent.

Exclusion Criteria:

1. Systolic BP=190 mm Hg, or diastolic BP <60 mm Hg;

2. Known secondary cause of hypertension;

3. History of large atherosclerotic cerebral infarction or hemorrhagic stroke (not lacunar infarction and transient ischemic attack [TIA]);

4. Hospitalization for myocardial infarction or unstable angina within the previous 6 months;

5. Coronary revascularization (PCI or CABG) within the previous 12 months;

6. Planned to perform coronary revascularization (PCI or CABG) in the future 12 months;

7. History of sustained atrial fibrillation or Ventricular arrhythmias at entry influencing the measurement of electronic blood pressure;

8. NYHA class III-IV heart failure at entry or hospitalization for exacerbation of chronic heart failure within the previous 6 months;

9. Severe valvular disease or valvular disease likely to require surgery or percutaneous valve replacement during the trial;

10. Dilated or hypertrophic cardiomyopathy, rheumatic heart disease, or congenital heart disease;

11. Uncontrolled diabetes (serum fasting glucose =200 mg/dl [11.1 mmol/L], HbA1>8%);

12. 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];

13. Severe somatic disease such as cancer;

14. Severe cognitive impairment or mental disorders;

15. Participating in other clinical trials.

Related Conditions & MeSH terms

• Essential Hypertension
• Primary Hypertension

Intervention

Drug:
• Intensive BP control
For all participants, Olmesartan Medoxomil tablets or Amlodipine Besylate tablets will be used as an initial therapy. Other drugs, including hydrochlorothiazide and ß-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.
• Standard BP control
For all participants, Olmesartan Medoxomil tablets or Amlodipine Besylate tablets will be used as an initial therapy. Other drugs, including hydrochlorothiazide and ß-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.

Locations

Country	Name	City	State
China	The Second Affiliated Hospital of Baotou Medical College	Baotou	Inner Mongolia
China	Bei Jing Hospital	Beijing	Beijing
China	Beijing Chaoyang Hospital affiliated to Capical Medical University	Beijing	Beijing
China	Beijing Pinggu Hospital	Beijing	Beijing
China	Chinese Academy of Medical Sciences, FuWai Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Xuanwu hospital of capital medical university	Beijing	Beijing
China	Benxi Railway Hospital	Benxi	Liaoning
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	The 1st Affiliated Hospital of Dalian Medical University	Dalian	Liaoning
China	Guangdong Cardiovascular Institute	Guangzhou	Guangdong
China	First affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Huizhou Municipal Central Hospital	Huizhou	Guangdong
China	Qilu Hospital of Shandong University	Jinan	Shandong
China	Jining First People's Hospital	Jining	Shandong
China	The First Hospital of Kunming	Kunming	Yunnan
China	The Second Affiliated Hospital of Kunming Medical University	Kunming	Yunnan
China	Yan'an Hospital affiliated to kunming medical university, Yunnan Cardiovascular Hospital	Kunming	Yunnan
China	Lanzhou University Second Hospital	Lanzhou	Gansu
China	the Second Affiliated Hospitalof NanChang University	Nanchang	Jiangxi
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	The First Affiliated Hospital of Guangxi University of Chinese Medicine	Nanning	Guangxi
China	Shanghai general hospital, Shanghai Jiaotong University	Shanghai	Shanghai
China	The Second Affiliated Hospital to Medical College Shantou University Guangdong	Shantou	Guangdong
China	Shenzhen Sun Yat-sen Cardiovascular Hospital	Shenzhen	Guangdong
China	Hong xinglong center hospital	Shuangyashan	Heilongjiang
China	College of Medicine , National Taiwan University	Taibei	Taiwan
China	First Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Shanxi Academy of Medical Sciences, Shanxi Dayi Hospital	Taiyuan	Shanxi
China	Shanxi caidiovascular hospital	Taiyuan	Shanxi
China	Kailua General Hospital	Tangshan	Hebei
China	Pingjin Hospital, Logistics University of PAPF	Tianjin	Tianjin
China	the People's Hospital of Ji Xian Distric	Tianjin	Tianjin
China	First Affiliated Hospital of Xinjiang Medical University	Urumqi	Xinjiang
China	Renmin Hospital of Wuhan University	Wuhan	Hubei
China	First Affiliated Hospital, Xian Jiaotong University	Xi'an	Shanxi
China	The First People's Hospital of Yinchuan	Yinchuan	Ningxia
China	Kang Ya Hospita	Yiyang	Hunan
China	The First Affiliated Hospital of Hebei North University	Zhangjiakou	Hebei
China	First Affiliated Hospitalof Zhengzhou University	Zhengzhou	Henan
China	Zhenjiang First People's Hospital	Zhenjiang	Jiangsu
China	Zhoukou City Central Hospital	Zhoukou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Chinese Academy of Medical Sciences, Fuwai Hospital

Country where clinical trial is conducted

China, 

References & Publications (5)

ACCORD Study Group, Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, Cutler JA, Simons-Morton DG, Basile JN, Corson MA, Probstfield JL, Katz L, Peterson KA, Friedewald WT, Buse JB, Bigger JT, Gerstein HC, Ismail-Beigi F. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010 Apr 29;362(17):1575-85. doi: 10.1056/NEJMoa1001286. Epub 2010 Mar 14. — View Citation

JATOS Study Group. Principal results of the Japanese trial to assess optimal systolic blood pressure in elderly hypertensive patients (JATOS). Hypertens Res. 2008 Dec;31(12):2115-27. doi: 10.1291/hypres.31.2115. — View Citation

Probstfield JL, Applegate WB, Borhani NO, Curb JD, Cutler JA, Davis BR, Furberg CD, Hawkins CM, Lakatos E, Page LB, et al. The Systolic Hypertension in the Elderly Program (SHEP): an intervention trial on isolated systolic hypertension. SHEP Cooperative Research Group. Clin Exp Hypertens A. 1989;11(5-6):973-89. — View Citation

SPRINT Research Group, Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, Reboussin DM, Rahman M, Oparil S, Lewis CE, Kimmel PL, Johnson KC, Goff DC Jr, Fine LJ, Cutler JA, Cushman WC, Cheung AK, Ambrosius WT. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 2015 Nov 26;373(22):2103-16. doi: 10.1056/NEJMoa1511939. Epub 2015 Nov 9. Erratum in: N Engl J Med. 2017 Dec 21;377(25):2506. — View Citation

Wang Y, Peng X, Nie X, Chen L, Weldon R, Zhang W, Xiao D, Cai J. Burden of hypertension in China over the past decades: Systematic analysis of prevalence, treatment and control of hypertension. Eur J Prev Cardiol. 2016 May;23(8):792-800. doi: 10.1177/2047487315617105. Epub 2015 Nov 24. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Cardiovascular death	Cardiovascular death includes fatal coronary heart disease, fatal stroke, death from heart failure, and sudden cardiac death.	4 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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