Feasibility Study of the Intensive Systolic Blood Pressure Control

Effects of Intensive Antihypertensive Therapies on the Risk of Stroke in Hypertensive Adults: A Prospective Randomized Open-Label Blinded-Endpoint Trial, a Feasibility Study

The purpose of the current feasibility study is to test whether the blood pressure level of the study patients can be effectively and safely managed according to the intensive antihypertensive treatment protocol. Furthermore, the study will also examine the effect of intensive antihypertensive treatment on the intermediate cardiovascular diseases outcomes, including CIMT, carotid plaques, PWV ABI, and kidney function, etc.

Study Overview

• Status: Unknown
• Conditions: Hypertension; Hyperhomocysteinemia
• Intervention / Treatment: Drug: Standard BP control; Drug: Moderate BP control; Drug: Intensive BP control

Detailed Description

The China Stroke Primary Prevention Trial (CSPPT, NCT00794885) found that among hypertensive adults in China without a history of stroke or myocardial infarction, the combined use of enalapril and folic acid, compared with enalapril alone, significantly reduced the risk of first stroke. The mean systolic blood pressures were highly comparable between the two groups over the course of the trial (139.7mmHg and 139.8mmHg, respectively, in the enalapril-folic acid and the enalapril group). In the further analysis, lower systolic blood pressures seemed to be associated with greater reduction in cardiovascular outcomes in both of the treatment groups.

However, due to inconsistencies in the results of the ACCORD and SPRINT trials, the appropriate targets for systolic blood pressure in effectively reducing cardiovascular events among hypertensive patients remain uncertain.

The proposed trial aims to test the hypothesis that among hypertensive patients aged 60 years or older, a lower systolic blood pressure goal will lead to greater reduction in stroke incidence.

The current feasibility study aims to test whether the blood pressure level of the study patients can be effectively and safely managed according to the intensive antihypertensive treatment protocol. Furthermore, the study will also examine the effect of intensive antihypertensive treatment on the intermediate cardiovascular diseases outcomes, including CIMT, carotid plaques, PWV ABI, and kidney function, etc.

The current feasibility study will enroll approximately 100 patients with H-type hypertension (hypertensive patients with hyperhomocysteinemia) aged 60 years or older, and without a history of major cardiovascular diseases.

Eligible patients will randomly assigned to one of three different systolic blood pressure (SBP) target groups (Group A, SBP: 140 - <150 mmHg; Group B, SBP: 130 - < 140 mmHg; and Group C, SBP < 130 mmHg).

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shandong
    • Rongcheng, Shandong, China, 264300
      • the People's Hospital of Rongcheng

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Hypertensive patients aged 60 years or older.
• SBP>= 150 mmHg but <180 mmHg, if currently (within the previous two weeks) not regularly treated with antihypertensive drugs.
• If currently (at least 10 days on medications within the previous two weeks) regularly treated with antihypertensive drugs, blood pressure must meet the following criteria:

SBP >= 140 mmHg but <170 mmHg, if regularly (no less than 10 days) taking 1 type of antihypertensive medication within the previous two weeks; SBP >= 130 mmHg but <160 mmHg, if regularly (no less than 10 days) taking 2 types of antihypertensive medications within the previous two weeks; SBP >= 130 mmHg but <150 mmHg, if regularly (no less than 10 days) taking 3 types of antihypertensive medication within the previous two weeks.

For patients taking a fixed-dose-combination (FDC), this treatment will be considered as two types of drugs if the dose of each component of the FDC is equal to higher than the routine therapeutic dose.

• Blood homocysteine (Hcy)≥ 10μmol/L, or the patient is taking enalapril-folic acid;
• Subject has read and signed a written, informed consent form.

Exclusion Criteria:

• History of physician diagnosed stroke, myocardial infarction, heart failure, revascularization, or malignancy;
• Clearly diagnosed secondary hypertension;
• Undergoing regular renal dialysis or has been diagnosed with end-stage kidney disease;
• Congenital or acquired organic heart disease;
• Severe somatic disease preventing the participant from completing the trial, or based on the discretion of the investigators, the patient is incapable of participating;
• Contraindicated or intolerable to ACEIs (including enalapril-folic acid) or a history of severe adverse effects to ACEIs;
• Individuals with abnormal laboratory test results and/or clinical manifestations rendering them unsuitable to participate as judged by the investigators;
• Any factor likely to limit adherence to interventions or jeopardize data collection, for example: dementia, severe mental disorders impeding expression or communication abilities, an inability to adhere the follow-up plan, plans to move in the near future, or, a history of unreliability in following a medication regimen or in keeping appointments;
• Living with a family member (a spouse, for example) who has already participated in the study;
• Unwilling to participate, unwilling or unable to change current therapeutic regimen;
• Currently (or within one month) participating in another new drug trial.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Standard BP control; SBP within 140 - <150 mmHg. For all participants, enalapril-folic acid will be used as an initial therapy. Other drugs, including CCB (amlodipine preferred), diuretics (hydrochlorothiazide preferred), and β-blockers, are allowed, in order to achieve the SBP target. For those who can't tolerate enalapril-folic acid well, other types of antihypertensive agents may be used as alternative choices. If the target BP level is not achieved during the Titration or Follow-up periods, adjustment of drug type and dosage will be carried out according to procedures defined in the protocol.	Drug: Standard BP control; Enalapril-folic acid will be used as an initial therapy. Other drugs, including CCB (amlodipine preferred), diuretics (hydrochlorothiazide preferred), and β-blockers, are allowed, in order to achieve the SBP target.; Other Names: Enalapril-folic acid,amlodipine,hydrochlorothiazide
Active Comparator: Moderate BP control; SBP within 130 - <140 mmHg. For all participants, enalapril-folic acid will be used as an initial therapy. Other drugs, including CCB (amlodipine preferred), diuretics (hydrochlorothiazide preferred), and β-blockers, are allowed, in order to achieve the SBP target. For those who can't tolerate enalapril-folic acid well, other types of antihypertensive agents may be used as alternative choices. If the target BP level is not achieved during the Titration or Follow-up periods, adjustment of drug type and dosage will be carried out according to procedures defined in the protocol.	Drug: Moderate BP control; Enalapril-folic acid will be used as an initial therapy. Other drugs, including CCB (amlodipine preferred), diuretics (hydrochlorothiazide preferred), and β-blockers, are allowed, in order to achieve the SBP target.; Other Names: Enalapril-folic acid,amlodipine,hydrochlorothiazide
Active Comparator: Intensive BP control; SBP <130 mmHg. For all participants, enalapril-folic acid will be used as an initial therapy. Other drugs, including CCB (amlodipine preferred), diuretics (hydrochlorothiazide preferred), and β-blockers, are allowed, in order to achieve the SBP target. For those who can't tolerate enalapril-folic acid well, other types of antihypertensive agents may be used as alternative choices. If the target BP level is not achieved during the Titration or Follow-up periods, adjustment of drug type and dosage will be carried out according to procedures defined in the protocol.	Drug: Intensive BP control; Enalapril-folic acid will be used as an initial therapy. Other drugs, including CCB (amlodipine preferred), diuretics (hydrochlorothiazide preferred), and β-blockers, are allowed, in order to achieve the SBP target.; Other Names: Enalapril-folic acid,amlodipine,hydrochlorothiazide

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Achieved mean blood pressure levels in each of the treatment groups	6 months BP titration treatment period

Secondary Outcome Measures

Outcome Measure	Time Frame
Carotid intima-media thickness (CIMT), Carotid plaques	6 months BP titration treatment period
Carotid-femoral pulse wave velocity, Brachial-ankle pulse wave velocity	6 months BP titration treatment period
Ankle brachial index	6 months BP titration treatment period
Urinary albumin-creatinine ratio	6 months BP titration treatment period

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Events related to the intensive blood pressure control, Hypotension, Syncope, Bradycardia or Arrhythmia, Hyperkalemia, Renal Failure		6 months BP titration treatment period
First Occurrence of a Major Cardiovascular Event (MCE); Specifically Nonfatal Heart Attack, Nonfatal Stroke, or Cardiovascular Death hospitalization; Hospitalization	6 months BP titration treatment period	during the Randomization and Titration Treatment period

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital of Nanchang University
• Collaborators: Peking University First Hospital
• Investigators: Principal Investigator: Xiaoshu Cheng, MD, Second Affiliated Hospital of Nanchang University

Publications and helpful links

General Publications

• Huo Y, Li J, Qin X, Huang Y, Wang X, Gottesman RF, Tang G, Wang B, Chen D, He M, Fu J, Cai Y, Shi X, Zhang Y, Cui Y, Sun N, Li X, Cheng X, Wang J, Yang X, Yang T, Xiao C, Zhao G, Dong Q, Zhu D, Wang X, Ge J, Zhao L, Hu D, Liu L, Hou FF; CSPPT Investigators. Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial. JAMA. 2015 Apr 7;313(13):1325-35. doi: 10.1001/jama.2015.2274.
• Huang X, Liu L, Song Y, Gao L, Zhao M, Bao H, Qin X, Wu Y, Wu Q, Bi C, Yue A, Fang C, Ma H, Cui Y, Tang G, Li P, Zhang Y, Li J, Wang B, Xu X, Wang H, Parati G, Spence JD, Wang X, Huo Y, Chen G, Cheng X; investigators of intensive BP control in China. Achieving blood pressure control targets in hypertensive patients of rural China - a pilot randomized trial. Trials. 2020 Jun 11;21(1):515. doi: 10.1186/s13063-020-04368-1.

Study record dates

Study Major Dates

• Study Start: December 1, 2015
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: June 18, 2016
• First Submitted That Met QC Criteria: June 24, 2016
• First Posted (Estimate): June 29, 2016

Study Record Updates

• Last Update Posted (Estimate): October 14, 2016
• Last Update Submitted That Met QC Criteria: October 13, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: China; hypertension; primary prevention; BP titration; intensive blood pressure control; H-type Hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Nutrition Disorders; Genetic Diseases, Inborn; Avitaminosis; Deficiency Diseases; Malnutrition; Metabolism, Inborn Errors; Malabsorption Syndromes; Amino Acid Metabolism, Inborn Errors; Vitamin B Deficiency; Hypertension; Hyperhomocysteinemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Vasodilator Agents; Enzyme Inhibitors; Protease Inhibitors; Natriuretic Agents; Micronutrients; Membrane Transport Modulators; Diuretics; Vitamins; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Hematinics; Angiotensin-Converting Enzyme Inhibitors; Sodium Chloride Symporter Inhibitors; Amlodipine; Enalaprilat; Enalapril; Folic Acid; Vitamin B Complex; Hydrochlorothiazide
• Other Study ID Numbers: 20151BDH80038

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No