Clinical trial NCT04030234: Effects of Intensive Systolic Blood Pressure Lowering Treatment in Reducing RIsk of Vascular evenTs (ESPRIT) Study
Official title: Effects of Intensive Systolic Blood Pressure Lowering Treatment in Reducing RIsk of Vascular evenTs (ESPRIT) Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypertension
Keywords: Hypertension
Blood pressure target
Lead sponsor: China National Center for Cardiovascular Diseases
Sponsor class: OTHER_GOV
First posted: 2019-07-23
Enrollment: 11255
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 trial aims to assess, in patients aged ≥50 years with an average baseline SBP ≥130 mmHg and a previous history of cardiovascular diseases or at high vascular risk, the effects on the incidence of major cardiovascular events during the scheduled treatment period of greater reduction in blood pressure with a SBP target \<120 mmHg versus \<140 mmHg.

Detailed description: This study is a multicenter, open-label, randomized controlled trial, which will randomize participants aged ≥50 years with an average baseline SBP ≥130 mmHg and a previous history of cardiovascular diseases or at high vascular risk. The study will compare the effects on the incidence of major cardiovascular events of allocation to achieve an intensive SBP goal (SBP \<120 mmHg) with a standard SBP goal (SBP \<140 mmHg) in four years of follow up.

Eligibility criteria: Inclusion Criteria:

1. At least ≥50 years old, and
2. Systolic blood pressure (SBP): (having documentation of SBP to meet the criteria below on 2 consecutive visits)

   * SBP: 130-180 mmHg on 0 or 1 medication
   * SBP: 130-170 mmHg on up to 2 medications
   * SBP: 130-160 mmHg on up to 3 medications
   * SBP: 130-150 mmHg on up to 4 medications, and
3. Prior vascular disease or at high vascular risk

   1. Previous myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), at least a 50% diameter stenosis of a coronary, chest pain with objective evidence of myocardial ischemia (load electrocardiogram or load image examination indicated myocardial ischemia)
   2. Previous stroke
   3. Carotid endarterectomy (CE), or carotid stenting
   4. Peripheral artery disease (PAD) with revascularization
   5. Abdominal aortic aneurysm (AAA) ≥5 cm with repair
   6. Combine with no less than two risk factors below

      * ≥60 years old male or ≥65 years old female
      * Diabetes
      * Dyslipidemia (total cholesterol \>200 mg/dL \[5.2 mmol/L\] or LDL-C \>130 mg/dL \[3.4 mmol/L\] or HDL-C \< 40 mg/dL \[1.0 mmol/L\])
      * Current smoking (smoke more than a cigarette every day in the past 12 months)

Exclusion Criteria:

1. Known secondary cause of hypertension
2. An indication for a specific BP lowering medication that the participant is not taking and the participant has not been documented to be intolerant of the medication class
3. One minute standing SBP \<110 mmHg (not applicable if unable to stand)
4. Arm circumference too large or small to allow accurate blood pressure measurement with available devices
5. Proteinuria defined as urine dipstick ≥2+ protein at screening
6. Glomerulonephritis treated with or likely to be treated with immunosuppressive therapy
7. eGFR \<45 ml/min /1.73m2 or end-stage renal disease (ESRD)
8. Previous MI, stroke, or hospitalization for angina, PCI, CABG, CE or carotid stenting, PAD with revascularization, AAA≥5 cm with repair within last 3 months
9. Symptomatic heart failure within the past 6 months or documented left ventricular ejection fraction (by any method) \<35%
10. PCI or CABG planned for the next 6 months
11. A medical condition likely to limit survival to less than 3 years, or a cancer (other than non-melanoma skin cancer) diagnosed and treated within the past two years that, in the judgment of local clinical investigators, would compromise a participant's ability to comply with the protocol and complete the trial
12. Any organ transplant
13. Pregnancy, breast-feeding, or of child-bearing potential and not using adequate contraception
14. Any factors judged by local clinic investigators to be likely to limit adherence to interventions. For example,

    1. Active alcohol or substance abuse within the last 12 months
    2. Plans to move to another place to live for a long time
    3. Clinical diagnosis of dementia or mild cognitive impairment (MCI)
15. Currently participation in a clinical trial with an unlicensed drug or device
16. Living in the same household as an already randomized participant

Primary outcomes:
measure: Number of participants with composite of major CVD events
timeFrame: 4 years
Secondary outcomes:
measure: Number of participants with myocardial infarction
timeFrame: 4 years
measure: Number of participants with coronary revascularization
timeFrame: 4 years
measure: Number of participants with non-coronary revascularization
timeFrame: 4 years
measure: Number of participants with chronic or acute decompensated heart failure hospitalization or emergency department visit
timeFrame: 4 years
measure: Number of participants with stroke
timeFrame: 4 years
measure: Number of participants with cardiovascular death
timeFrame: 4 years
measure: Number of participants with all-cause death
timeFrame: 4 years
measure: Number of participants with composite outcome of the primary composite with all-cause death
timeFrame: 4 years
measure: Number of participants with end-stage kidney disease (ESKD), a sustained decline in eGFR to <10 mL/min/1.73m2, renal death, or a sustained decline of ≥40% in eGFR from randomization
timeFrame: 4 years
measure: Number of participants with all-cause dementia or mild cognitive impairment
timeFrame: 4 years
measure: Difference of arteriole-to-venule ratio measured by fundus photography between intensive treatment group and standard treatment group
timeFrame: at 4-year final follow-up visit
Other outcomes:
Locations:
city: Beijing
country: China
facility: Fuwai Hospital, Chinese Academy of Medical Sciences
Study officials:
affiliation: National Center for Cardiovascular Diseases
name: Jing Li, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Center for Cardiovascular Diseases
name: Jiamin Liu, MD
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.