A Prospective, Multicentre, Randomized, Open Label, Evaluator-Blind, Phase IV Study to Evaluate the Effect on Improvement of Left Ventricular Hypertrophy by the Control of Blood Pressure in Hypertension Patients With Aortic Valve Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 128
- 试验地点
- 1
- 主要终点
- To evaluate changes from baseline in Left Ventricular Mass at 24M
研究概览
简要总结
To compare changes in Left Ventricular Mass (LVM) depending on each blood pressure regulation between the intensive care group and the usual care group for patients with hypertension accompanied by aortic valve disease and evaluate an influence of blood pressure regulation on improvement of left ventricular hypertrophy and its safety
详细描述
1.Primary objectives
- To evaluate changes from baseline in LVM at V5 (24M)
2.Secondary objectives
- To evaluate changes from baseline in LV global longitudinal strain at V5 (24M)
- To evaluate changes from baseline in E/E' (E: early diastolic LV inflow velocity, E': early diastolic mitral annulus velocity) at V5 (24M)
- To evaluate changes from baseline in LV volumes, a stroke volume index and LV ejection fraction at V5 (24M)
- To evaluate a rate of disease progression
- In case of Aortic stenosis (AS), to evaluate changes from baseline in Aortic Valve Area (AVA), Vmax, Mean Pressure Gradient (PG) and Valvulo-arterial impedance (Zva) at V5 (24M)
- In case of Aortic regurgitation (AR), to evaluate changes from baseline in Vena contracta at V5 (24M)
- To evaluate changes from baseline in blood pressure at V2(6M), V3(12M), V4(18M) and V5(24M)
- To evaluate a cumulative incidence rate for each visit time point
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 19 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged ≥ 19 years and < 80 years
- •Diagnosis of mild-moderate AS or mild-moderate AR
- •Applicable to 2.0~3.9 m/s of aortic jet velocity for mild-moderate AS or to 0.2~0.6 cm of Vena contracta for mild-moderate AR
- •Diagnosis of hypertension (SBP > 130 mmHg if being treated or SBP > 140 mmHg if being untreated)
- •For females of childbearing potential; negative pregnancy test results during the screening period and prior to administration of the investigational product, and agreement on use of medically allowable contraceptive measures (condom, oral contraceptive pills, injectable or implantable contraceptives, intrauterine devices, birth control patches, etc.) during the study period
- •Voluntary written consent to taking part in the clinical study and willingness to comply with requirements of the study
排除标准
- •History of a cardiac valve replacement surgery (replacement surgery of mitral valve, aortic valve or tricuspid valve)
- •Accompanied by severe mitral regurgitation
- •Admitted to needing a surgery by the current treatment guidelines
- •Accompanied by symptoms such as angina pectoris, exertional dyspnea, syncope, etc.
- •< 50% of left ventricular ejection fraction
- •History of hypersensitivity reaction to active ingredients of the investigational product (Amlodipine, Losartan and Chlorthalidone), dihydropyridine derivatives, thiazide drugs and other sulfonamide derivatives or their compositions
- •Pregnant or breastfeeding
- •Symptomatic orthostatic hypotension
- •Severe liver failure or renal failure (< 30 mL/min of creatinine clearance)
- •Hereditary angioedema or history of angioedema at treatment with ACE inhibitors or angiotensin II receptor blockers
- •Primary hyperaldosteronism
- •Genetic problems such as galactose intolerance, Lapp Lapp lactase deficiency or glucose-galactose malabsorption
- •Refractory hypokalemia
- •Hyponatremia or hypercalcemia
- •Symptomatic hyperuricemia (history of gout or uric acid lithiasis)
- •Untreated Addison's disease
- •Appropriately uncontrolled diabetes
- •Congenital or incurable hypertension
- •Diagnosis of severe cerebrovascular disorders (stroke, cerebral infarction, cerebral hemorrhage, etc.) within six months prior to the date of ICF obtainment
- •Wasting disease, autoimmune disease or connective tissue disease
- •Diagnosis of malignant tumor within five years prior to the date of ICF obtainment
- •Administration of another investigational product within four weeks prior to the date of ICF obtainment
- •For a patient who is taking anticoagulants and thrombolytic agents; considered difficult to keep a stable dosage/regimen by the investigator.
- •Considered unsuitable to be a subject by the investigator
研究组 & 干预措施
The intensive care group
The intensive care group is targeted at ≤ 130 mmHg of systolic blood pressure, and treatment is done by changing the current treatment to the investigational product.
In case of treatment with the investigational product (IP), the IP titration period is total six months. According to an IP titration scheme(Amlodipine 5 mg or Losartan 50 mg -> Losartan and Amlodipine 5/50 mg -> Losartan and Amlodipine 5/100 mg -> Amlodipine/Losartan/Chlorthalidone 5/100/12.5 mg), IP is successively modified until the target blood pressure is reached, and IP will remain the same after the target blood pressure scope for each group is reached. An IP titration interval is decided by the investigator depending on the subject's condition.
干预措施: Amlodipine 5mg (Drug)
The intensive care group
The intensive care group is targeted at ≤ 130 mmHg of systolic blood pressure, and treatment is done by changing the current treatment to the investigational product.
In case of treatment with the investigational product (IP), the IP titration period is total six months. According to an IP titration scheme(Amlodipine 5 mg or Losartan 50 mg -> Losartan and Amlodipine 5/50 mg -> Losartan and Amlodipine 5/100 mg -> Amlodipine/Losartan/Chlorthalidone 5/100/12.5 mg), IP is successively modified until the target blood pressure is reached, and IP will remain the same after the target blood pressure scope for each group is reached. An IP titration interval is decided by the investigator depending on the subject's condition.
干预措施: Losartan (Drug)
The intensive care group
The intensive care group is targeted at ≤ 130 mmHg of systolic blood pressure, and treatment is done by changing the current treatment to the investigational product.
In case of treatment with the investigational product (IP), the IP titration period is total six months. According to an IP titration scheme(Amlodipine 5 mg or Losartan 50 mg -> Losartan and Amlodipine 5/50 mg -> Losartan and Amlodipine 5/100 mg -> Amlodipine/Losartan/Chlorthalidone 5/100/12.5 mg), IP is successively modified until the target blood pressure is reached, and IP will remain the same after the target blood pressure scope for each group is reached. An IP titration interval is decided by the investigator depending on the subject's condition.
干预措施: Losartan and Amlodipine (Drug)
The intensive care group
The intensive care group is targeted at ≤ 130 mmHg of systolic blood pressure, and treatment is done by changing the current treatment to the investigational product.
In case of treatment with the investigational product (IP), the IP titration period is total six months. According to an IP titration scheme(Amlodipine 5 mg or Losartan 50 mg -> Losartan and Amlodipine 5/50 mg -> Losartan and Amlodipine 5/100 mg -> Amlodipine/Losartan/Chlorthalidone 5/100/12.5 mg), IP is successively modified until the target blood pressure is reached, and IP will remain the same after the target blood pressure scope for each group is reached. An IP titration interval is decided by the investigator depending on the subject's condition.
干预措施: Amlodipine/Losartan/Chlorthalidone (Drug)
The usual care group
The usual care group is targeted at ≤ 140 mmHg of systolic blood pressure, and treatment is done by maintaining the current treatment, adding the investigational product, or changing the current treatment to the investigational product.
In case of treatment with the investigational product (IP), the IP titration period is total six months. According to an IP titration scheme(Amlodipine 5 mg or Losartan 50 mg -> Losartan and Amlodipine 5/50 mg -> Losartan and Amlodipine 5/100 mg -> Amlodipine/Losartan/Chlorthalidone 5/100/12.5 mg), IP is successively modified until the target blood pressure is reached, and IP will remain the same after the target blood pressure scope for each group is reached. An IP titration interval is decided by the investigator depending on the subject's condition.
干预措施: Amlodipine 5mg (Drug)
The usual care group
The usual care group is targeted at ≤ 140 mmHg of systolic blood pressure, and treatment is done by maintaining the current treatment, adding the investigational product, or changing the current treatment to the investigational product.
In case of treatment with the investigational product (IP), the IP titration period is total six months. According to an IP titration scheme(Amlodipine 5 mg or Losartan 50 mg -> Losartan and Amlodipine 5/50 mg -> Losartan and Amlodipine 5/100 mg -> Amlodipine/Losartan/Chlorthalidone 5/100/12.5 mg), IP is successively modified until the target blood pressure is reached, and IP will remain the same after the target blood pressure scope for each group is reached. An IP titration interval is decided by the investigator depending on the subject's condition.
干预措施: Losartan (Drug)
The usual care group
The usual care group is targeted at ≤ 140 mmHg of systolic blood pressure, and treatment is done by maintaining the current treatment, adding the investigational product, or changing the current treatment to the investigational product.
In case of treatment with the investigational product (IP), the IP titration period is total six months. According to an IP titration scheme(Amlodipine 5 mg or Losartan 50 mg -> Losartan and Amlodipine 5/50 mg -> Losartan and Amlodipine 5/100 mg -> Amlodipine/Losartan/Chlorthalidone 5/100/12.5 mg), IP is successively modified until the target blood pressure is reached, and IP will remain the same after the target blood pressure scope for each group is reached. An IP titration interval is decided by the investigator depending on the subject's condition.
干预措施: Losartan and Amlodipine (Drug)
The usual care group
The usual care group is targeted at ≤ 140 mmHg of systolic blood pressure, and treatment is done by maintaining the current treatment, adding the investigational product, or changing the current treatment to the investigational product.
In case of treatment with the investigational product (IP), the IP titration period is total six months. According to an IP titration scheme(Amlodipine 5 mg or Losartan 50 mg -> Losartan and Amlodipine 5/50 mg -> Losartan and Amlodipine 5/100 mg -> Amlodipine/Losartan/Chlorthalidone 5/100/12.5 mg), IP is successively modified until the target blood pressure is reached, and IP will remain the same after the target blood pressure scope for each group is reached. An IP titration interval is decided by the investigator depending on the subject's condition.
干预措施: Amlodipine/Losartan/Chlorthalidone (Drug)
The usual care group
The usual care group is targeted at ≤ 140 mmHg of systolic blood pressure, and treatment is done by maintaining the current treatment, adding the investigational product, or changing the current treatment to the investigational product.
In case of treatment with the investigational product (IP), the IP titration period is total six months. According to an IP titration scheme(Amlodipine 5 mg or Losartan 50 mg -> Losartan and Amlodipine 5/50 mg -> Losartan and Amlodipine 5/100 mg -> Amlodipine/Losartan/Chlorthalidone 5/100/12.5 mg), IP is successively modified until the target blood pressure is reached, and IP will remain the same after the target blood pressure scope for each group is reached. An IP titration interval is decided by the investigator depending on the subject's condition.
干预措施: current treatment (Drug)
结局指标
主要结局
To evaluate changes from baseline in Left Ventricular Mass at 24M
时间窗: 24 months
To evaluate changes from baseline in Left Ventricular Mass at 24M
次要结局
- Changes from baseline in Left Ventricular global longitudinal strain at 24M(24 months)
- Changes from baseline in E/E' (E: early diastolic LV inflow velocity, E': early diastolic mitral annulus velocity) at 24M(24 months)
- Changes from baseline in Left Ventricular volumes at 24M(24 months)
- Rate of disease progression(24 months)
- To evaluate changes from baseline in systolic blood pressure at 6M, 12M, 18M, 24M(6 months, 12 months, 18 months, 24 months)
- Cumulative incidence rate for each visit time point(6 months, 12 months, 18 months, 24 months)
- Changes from baseline in stroke volume index at 24M(24 months)
- Changes from baseline in Left Ventricular ejection fraction at 24M(24 months)