Optimal Medical Treatment of Difficult-to-treat Hypertension
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 2,500
- 试验地点
- 2
- 主要终点
- Patients with uncontrolled BP on ABPM
研究概览
简要总结
The purpose of this study is to evaluate best medical management to achieve the BP goals of ESC/ESH (120-129 / 70-79 mmHg) in HT patients who are <65 years old and ineffectively treated (BP ≥ 130/80 mg) with 3 or more antihypertensive drugs
详细描述
Purpose: To evaluate best medical management to achieve the ESC/ESH 2018 BP goals of 120-129 / 70-79 mmHg in HT patients aged < 65 y not controlled on 3 or more antihypertensive drugs.
Study design:
Phase A (Active screening) (n = 2500) 7 days Confirmation of the true ineffectiveness of antihypertensive therapy based on 3 or more antihypertensive drugs (single or dual drug preparations) using ABPM and home BP measurements.
Phase B (Open-label, non-randomized) (n = 1250) 12 weeks Replacement of ineffective antihypertensive treatment based on 3 or more antihypertensive drugs (single or dual drug preparations) with a triple single pill combination (SPC) based on optimally combined antihypertensive drugs: perindopril + indapamide + amlodipine (P+I+A) or olmesartan + hydrocholothiazide + amlodipine (O+H+A).
Phase C (Double blind, randomized, parallel-group) (n = 480) 24 weeks
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •documented history of HT
- •HT treated for at least six months,
- •office BP ≥ 130 and / or ≥80 mm Hg (average seated BP at Visit 1)
- •use of 3 or more antihypertensive drugs, including an ACEi/ARB and a thiazide/thiazide-like diuretic or loop diuretic (single drugs or double SPCs)
- •stable antihypertensive treatment regimen - no changes in antihypertensive treatment strategy at least for 4 weeks
- •able and willing to comply with all study procedures and able to attend one of the study centers
排除标准
- •inability to give informed consent
- •SBP ≥180 mm Hg and/or DBP ≥110 mm Hg and/or DBP <60 mm Hg
- •BMI ≥40 kg/m2
- •eGFR of <45 mL/min/1.73 m2
- •potassium serum concentration > 4.8 mmol/L or < 3.5 mmol/L
- •persistent hyponatremia or history of hyponatremia related to TD/TLD treatment (sodium concentration <135 mmol/L)
- •secondary hypertension (not including sleep apnea)
- •chronic oral glucocorticoid therapy
- •myocardial infarction or cerebrovascular event (e.g. stroke, transient ischemic event, cerebrovascular accident) in the year prior to study inclusion
- •heart failure requiring treatment with diuretic or aldosterone antagonists
- •cardiomyopathy exluding LVH related to HT
- •severe valvular disease
- •ascending aortic aneurysm ≥5 cm
- •prescribed to any standard antihypertensive of cardiovascular medication (e.g. beta blockers) for other chronic conditions (e.g. chronic coronary syndromes, arytmia) such that discontinuation might pose serious risk to health
- •primary pulmonary hypertension
- •decompensated hyperthyroidism or hypothyroidism
- •severe liver dysfunction (alanine aminotransferase and/or asparagine aminotransferase activity ≥3 times the upper limit of normal value),
- •documented contraindication or allergy to studied drugs
- •limited life expectancy of < 1 year at the discretion of the Investigator
- •any known, unresolved history of drug use or alcohol dependency, lacks the ability to comprehend or follow instructions, or for any reason in the opinion of the investigator, would be unlikely or unable to comply with study protocol requirements
- •all women of child bearing potential; women of child bearing potential can be included in the study ONLY after providing documentation of effective contraception (intrauterine device);
- •concurrent enrollment in any other investigational drug or device trial
- •anticipated change of medical status during the trial (e.g., surgical intervention requiring >2 weeks convalescence)
- •current therapy for cancer
研究组 & 干预措施
Torasemide (+placebo of Eplerenone and placebo of Spironolactone )
Phase C. Participants randomly assigned to this arm take Torasemide and placebos of Eplerenone and Spironolactone
干预措施: Phase B: Triplixam / Elestar HCT (Drug)
Screening
Phase A. Confirmation of the true ineffectiveness of antihypertensive therapy based on 3 or more antihypertensive drugs (single or dual drug preparations) using ABPM and home BP measurements.
干预措施: Phase A: Confirmation of uncontrolled hypertension (Diagnostic Test)
Eplerenone (+placebo of Spironolactone and placebo of Torasemide)
Phase C. Participants randomly assigned to this arm take Eplerenone and placebos of Spironolactone and Torasemide
干预措施: Phase B: Triplixam / Elestar HCT (Drug)
Spironolactone (+placebo of Eplerenone and placebo of Torasemide)
Phase C. Participants randomly assigned to this arm take Spironolactone and placebos of Eplerenone and Torasemide
干预措施: Phase B: Triplixam / Elestar HCT (Drug)
Open-label
Phase B Replacement of ineffective antihypertensive treatment based on 3 or more antihypertensive drugs (single or dual drug preparations) with a triple single pill combination (SPC) based on optimally combined antihypertensive drugs: perindopril + indapamide + amlodipine (P+I+A) or olmesartan + hydrocholothiazide + amlodipine (O+H+A).
干预措施: Phase B: Triplixam / Elestar HCT (Drug)
结局指标
主要结局
Patients with uncontrolled BP on ABPM
时间窗: First week of the patients' participation in the study
Percentage of patients with uncontrolled BP confirmed on ABPM (24h mean, SBP ≥125 mm Hg or DBP ≥80 mm Hg)
Patients with controlled BP after 12 weeks on triple SPC
时间窗: Next 12 weeks of the patients' participation in the study
Percentage of patients with controlled BP after 12 weeks of treatment with triple SPC, confirmed on ABPM (24h mean, SBP \<125 mm Hg and DBP \<80 mm Hg) - as the efficacy of the treatment strategy (switching ineffective treatment to triple SPC) - the whole group and P+I+A and E+H+A groups separetly.
Systolic BP reduction on 4th antihypertensive drug
时间窗: Last 24 weeks of the patients' participation in the study
Magnitude of reduction of SBP on ABPM (24h mean) after 12 weeks of treatment - comparison of eplerenone vs spironolactone and torasemide vs spironolactone.
次要结局
- Percentage of patients with BP controlled confirmed by HBPM(First week of the patients' participation in the study)
- Consistency of the rate of uncontrolled BP(Next 12 weeks of the patients' participation in the study)
- Percentage of patients with controlled BP after 12 weeks of treatment, confirmed by OBPM(Last 24 weeks of the patients' participation in the study)
- Percentage of patients with controlled BP after 12 weeks of treatment, confirmed by HBPM(Last 24 weeks of the patients' participation in the study)
- Percentage of patients with controlled BP after 12 weeks of treatment, confirmed by ABPM(Last 24 weeks of the patients' participation in the study)
- Percentage of patients requiring an increase in the dose(Next 12 weeks of the patients' participation in the study)
- The magnitude of the decrease in SBP and DBP on OBPM, ABPM and HBPM after 12 weeks(Next 12 weeks of the patients' participation in the study)
- The magnitude of changes in HBPM and ABPM derived indices after 12 weeks(Next 12 weeks of the patients' participation in the study)
- Phase C(Last 24 weeks of the patients' participation in the study)
- Changes of SBP on ABPM (24h mean) after 12 weeks of treatment(Last 24 weeks of the patients' participation in the study)
- Changes in HBPM and ABPM derived indices after 12 weeks - comparison of treatment groups(Last 24 weeks of the patients' participation in the study)
- Changes of SBP on ABPM (24h mean) after 24 weeks of treatment compared against spironolactone(Last 24 weeks of the patients' participation in the study)
- Changes in HBPM and ABPM derived indices after 24 weeks of treatment - - comparison between groups(Last 24 weeks of the patients' participation in the study)
- Changes of SBP on ABPM (24h mean) after 24 weeks of treatment compared against baseline(Last 24 weeks of the patients' participation in the study)
- Percentage of patients with controlled BP after 24 weeks of treatment, confirmed by OBPM - comparison between groups(Last 24 weeks of the patients' participation in the study)
- Percentage of patients with controlled BP after 24 weeks of treatment, confirmed by HBPM - comparison between groups(Last 24 weeks of the patients' participation in the study)
- Percentage of patients with controlled BP after 24 weeks of treatment, confirmed by ABPM - comparison between groups(Last 24 weeks of the patients' participation in the study)
- Consistency of the rate of controlled BP between ABPM, HBPM and OBPM after 24 weeks(Last 24 weeks of the patients' participation in the study)
- Changes in SBP and DBP on OBPM, ABPM and HBPM after 24 weeks of treatment - comparison between groups(Last 24 weeks of the patients' participation in the study)
- Percentage of patients requiring an increase in the dose of drugs used after 6 and 12 weeks - comparison between groups(Last 24 weeks of the patients' participation in the study)
- Phase C continuation(Last 24 weeks of the patients' participation in the study)