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

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.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Intensive BP treatment group; Drug: Standard BP treatment group

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 Type: Interventional
• Enrollment (Actual): 11255
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100087
    • Fuwai Hospital, Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intensive 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.	Drug: Intensive BP treatment group; Participants in the Intensive BP treatment group have a goal of SBP <120 mmHg. It is recommended to provide long-acting antihypertensive medications, that is once daily, unless other medication delivery frequency is needed. The local investigator may select among the available study antihypertensive medications. Other drugs not supplied by the trial may also be used as the investigator determines appropriate. One or more medications from the following classes of agents will be provided by the study for use in managing participants in both randomization groups to achieve study goals: Angiotension converting enzyme (ACE)-inhibitors; Angiotension receptor blockers (ARBs); Thiazide-type diuretics; Loop diuretics; Potassium-sparing diuretics; Beta-blockers; Calcium channel blockers (CCBs); Direct vasodilators; Alpha1-receptor blockers; Sympatholytics; Other Names: Control of SBP to <120 mmHg
Active Comparator: Standard 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.	Drug: Standard BP treatment group; Participants in the Standard BP treatment group have a goal of SBP <140 mmHg. The same medications used in the Intensive BP treatment group will be used for the Standard BP treatment group.; Other Names: Control of SBP to <140 mmHg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with composite of major CVD events	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	4 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with myocardial infarction	4 years
Number of participants with coronary revascularization	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
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
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

Collaborators and Investigators

• Sponsor: China National Center for Cardiovascular Diseases
• Investigators: Principal Investigator: Jing Li, MD, PhD, National Center for Cardiovascular Diseases; Principal Investigator: Jiamin Liu, MD, National Center for Cardiovascular Diseases

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2019
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): July 14, 2023

Study Registration Dates

• First Submitted: July 17, 2019
• First Submitted That Met QC Criteria: July 21, 2019
• First Posted (Actual): July 23, 2019

Study Record Updates

• Last Update Posted (Actual): February 20, 2024
• Last Update Submitted That Met QC Criteria: February 17, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Hypertension; Blood pressure target
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: 2018YFC1312400

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No