Effects of Intensive Systolic Blood Pressure Lowering Treatment in Reducing RIsk of Vascular evenTs (ESPRIT) Study

Not Applicable

Completed

• Conditions: Hypertension
• Interventions: Drug: Intensive BP treatment group; Drug: Standard BP treatment group

• Registration Number: NCT04030234
• Lead Sponsor: China National Center for Cardiovascular Diseases

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.

Study Timeline

• Study First Submitted: 2019-07-17
• Study First Submitted QC: 2019-07-21
• Study First Posted: 2019-07-23
• Study Start: 2019-09-17
• Primary Completion: 2023-06-30
• Study Completion: 2023-07-14
• Status Verified: 2024-01
• Last Update Submitted: 2024-02-17
• Last Update Posted: 2024-02-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11255

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intensive treatment group	Intensive BP treatment group	Participants randomized into the Intensive treatment group will have a goal of SBP \<120 mmHg. A two- or three-drug regimen should be initiated at randomization for most participants. Drug doses should be increased and/or additional antihypertensive medications should be added at each visit in the intensive treatment group, usually at monthly intervals, until the participant's goal of \<120 mmHg has been reached or the local investigator decides no further antihypertensive medications may be added.
Standard treatment group	Standard BP treatment group	Participants randomized into the Standard treatment group will have a goal of SBP \<140 mmHg. It is expected to achieve a SBP of 135-139 mmHg in as many participants as possible. Medication dose titration or addition of another drug is indicated if SBP is ≥160 mmHg at a single visit or is ≥140 mmHg at two consecutive visits. Down titration should be carried out if the SBP is \<130 mmHg at a single visit or \<135 mmHg at two consecutive visits.

Primary Outcome Measures

Name	Time	Method
Number of participants with composite of major CVD events	4 years	Composite outcome of myocardial infarction, coronary or non-coronary revascularization, chronic or acute decompensated heart failure hospitalization or emergency department visit, stroke, or death from cardiovascular disease

Secondary Outcome Measures

Name	Time	Method
Number of participants with coronary revascularization	4 years
Difference of arteriole-to-venule ratio measured by fundus photography between intensive treatment group and standard treatment group	at 4-year final follow-up visit
Number of participants with myocardial infarction	4 years
Number of participants with all-cause death	4 years
Number of participants with composite outcome of the primary composite with all-cause death	4 years
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	4 years
Number of participants with all-cause dementia or mild cognitive impairment	4 years
Number of participants with non-coronary revascularization	4 years
Number of participants with chronic or acute decompensated heart failure hospitalization or emergency department visit	4 years
Number of participants with stroke	4 years
Number of participants with cardiovascular death	4 years

Trial Locations

Locations (1)

Fuwai Hospital, Chinese Academy of Medical Sciences; 🇨🇳 Beijing, China