Clinical trial NCT02817503: Feasibility Study of the Intensive Systolic Blood Pressure Control
Official title: Effects of Intensive Antihypertensive Therapies on the Risk of Stroke in Hypertensive Adults: A Prospective Randomized Open-Label Blinded-Endpoint Trial, a Feasibility Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hypertension
Hyperhomocysteinemia
Keywords: hypertension
BP titration
intensive blood pressure control
primary prevention
China
H-type Hypertension
Lead sponsor: Second Affiliated Hospital of Nanchang University
Sponsor class: OTHER
Collaborators: name: Peking University First Hospital
First posted: 2016-06-29
Enrollment: 100
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Achieved mean blood pressure levels in each of the treatment groups
timeFrame: 6 months BP titration treatment period
Secondary outcomes:
measure: Carotid intima-media thickness (CIMT), Carotid plaques
timeFrame: 6 months BP titration treatment period
measure: Carotid-femoral pulse wave velocity, Brachial-ankle pulse wave velocity
timeFrame: 6 months BP titration treatment period
measure: Ankle brachial index
timeFrame: 6 months BP titration treatment period
measure: Urinary albumin-creatinine ratio
timeFrame: 6 months BP titration treatment period
Other outcomes:
measure: Events related to the intensive blood pressure control, Hypotension, Syncope, Bradycardia or Arrhythmia, Hyperkalemia, Renal Failure
timeFrame: 6 months BP titration treatment period
measure: First Occurrence of a Major Cardiovascular Event (MCE); Specifically Nonfatal Heart Attack, Nonfatal Stroke, or Cardiovascular Death hospitalization; Hospitalization
timeFrame: during the Randomization and Titration Treatment period
Locations:
city: Rongcheng
country: China
facility: the People's Hospital of Rongcheng
state: Shandong
Study officials:
affiliation: Second Affiliated Hospital of Nanchang University
name: Xiaoshu Cheng, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.