The Precision Hypertension Care Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 280
- 试验地点
- 1
- 主要终点
- Between-person variation in blood pressure-lowering effects of blood pressure-lowering drugs, measured as variation in daytime (10 a.m. to 8 p.m.) ambulatory systolic blood pressure.
研究概览
简要总结
The PHYSIC study aims to investigate the potential for precision medicine in the treatment of high blood pressure.
It is a double-blind, randomized, repeated cross-over trial with six treatment periods: four classes of blood pressure-lowering drugs where treatment with two classes are repeated for each patient. The classes of blood pressure-lowering drugs to be tested are a diuretic, a calcium channel blocker, an ACE-inhibitor and an angiotensin receptor blocker.
详细描述
It is unknown if there is a clinically relevant between-person difference in blood pressure response to a given drug, i.e. if there are responders and non-responders to the drug. If there is no major between-person variation in blood pressure response or side effects of a drug, then there is no potential for precision medicine. It is also unknown if between- person differences in blood pressure response are different for different drugs, and magnitudes of within- and between-person variations in side effects are particularly unknown. Resolving these issues are imperative for the possibilities of precision blood pressure-lowering treatment, and this study aims to initially answer those questions.
If this study proves that there is potential for personalized blood pressure-lowering treatment, investigators will explore the most promising predictors of blood pressure and side effect response to the four major first-line classes of blood pressure-lowering drugs, using several modalities of -omics methods in combination with clinical data. Using these data, investigators will develop and evaluate a point-of-care biomarker panel which will rank the suitability of each of the blood pressure-lowering drug classes for the individual patient in terms of both anticipated blood pressure effect and side effects, thereby providing a suggestion of the priority of the drugs.
The PHYSIC study is a double-blind, randomized, repeated cross-over trial with six treatment periods: four classes of blood pressure-lowering drugs where treatment with two classes are repeated for each patient. The classes of blood pressure-lowering drugs to be tested are a diuretic, a calcium channel blocker, an ACE-inhibitor and an angiotensin receptor blocker. The repeated treatment periods allow investigators to assess whether there is consistent preference of one treatment over another within a blinded patient under different treatment periods. This is a key but often overlooked element in the exploration of the potential for precision medicine.
Evidence-based titration and target doses have been chosen for all four drug classes included. The suggested treatment duration of 7-9 weeks per treatment arm is based on recent guidelines. Patients will be assigned a treatment order based on block randomization ensuring that the same number of patients will repeat each pair of treatments. The study tests several pre-defined hypotheses, which will not be adjusted for multiple testing. The main outcome variable will be variation in daytime ambulatory systolic blood pressure assessed in a blinded fashion.
The screening visit (visit 1) will occur at least two weeks before randomization (visit 2). At screening, consenting patients are assessed to ensure that they meet eligibility criteria initially. Patients who do not meet these criteria must not be enrolled in the study. Patients who do meet these criteria are allocated an enrolment number. The amount of assessment made at this visit includes consent procedures, weight, height, waist, and hip circumference, physical examination, concomitant medication, blood pressure, and blood sampling for safety assessment and DNA genetics. The patient will fill out two questionnaires covering medical history and beliefs about medicine. In order to be introduced to self-reporting symptoms and quality of life collected in electronic diary and get a baseline measurement patients will be asked to log in to and fill the diary under supervision of study staff.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female aged ≥40 years and ≤75 years
- •Previously diagnosed with hypertension with systolic blood pressure between 140 and 159 mm Hg within five years prior to the start of the trial.
- •Pharmacologically untreated or using blood pressure-lowering monotherapy at Visit
- •No blood pressure-lowering medication taken during the placebo run-in period.
- •Office systolic blood pressure between 140 and 179 mm Hg and diastolic blood pressure at or below 109 mm Hg at Visit
- •Patients must give informed consent to participate in the study.
排除标准
- •Medical history, clinical signs or laboratory results indicating secondary hypertension, including primary aldosteronism or renal artery stenosis
- •Evidence of serious hematological, respiratory immunological, renal, hepatic, gastrointestinal, endocrinological, metabolic, neurologic, malignant, psychiatric or other diseases as revealed by medical history, physical examination and/or laboratory assessments.
- •Active gout
- •Previous or present arterial occlusive diseases such as myocardial infarction (MI), stroke or acute arterial insufficiency (unstable angina pectoris or transient ischemic attacks, (TIA)) or heart failure (NYHA class III or IV, or left ventricular systolic dysfunction irrespectively of function class).
- •Moderate or severe aortic or mitral insufficiency.
- •Renal failure, including hemo-dialysis or kidney transplant/s.
- •Atrial fibrillation in need of rate control.
- •Symptomatic hypotension, defined as weakness or syncope upon rising to an erect position associated with a decrease in systolic blood pressure.
- •Diabetes requiring insulin or oral glucose-lowering drugs.
- •Any history of serious abnormal drug reaction to active or inactive compounds in the study drugs, including angioedema.
- •Any condition associated with poor compliance including alcoholism or drug dependence.
- •Patients who will not comply with the study protocol as judged by the Investigator.
- •Women who are pregnant or lactating or not using appropriate contraception for at least 3 months prior to visit
- •Acceptable contraceptive methods are: combined (estrogen and progesterone containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progesterone-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion and vasectomised partner.
- •Continuous use of concomitant medication that can interfere with study medication, i.e. digitalis glucosides, sotalol, cholestyramine, colestipol, NSAID, lithium, carbamazepine, CYP3A4-inhibitors, CYP3A4-inducers, dantrolene, diuretics, aliskiren, gold, sympathomimetics, tricyclic antidepressants, antipsychotics, anaesthetics and potassium supplements.
- •Clinical laboratory assessment outside normal range at visit 1 and judged clinically significant by the Investigator.
- •Previous randomization in present study
研究组 & 干预措施
Atacand® (Candesartan)
Angiotensin receptor blocker. Treatment step up: 1-2 weeks (8 mg tablet) Target dose: 5-7 weeks (16 mg tablet)
干预措施: Atacand® (Drug)
Zestril® (Lisinopril)
Inhibition of angiotensin converting enzyme (ACE inhibitor). Treatment step up: 1-2 weeks (10 mg tablet) Target dose: 5-7 weeks (20 mg tablet)
干预措施: Zestril® (Drug)
Norvasc® (Amlodipine)
Calcium channel blocker. Treatment step up: 1-2 weeks (5 mg tablet) Target dose: 5-7 weeks (10 mg tablet)
干预措施: Norvasc® (Drug)
Hydrochlorothiazide® (Hydrochlorothiazide)
Diuretic agent. Treatment step up: 1-2 weeks (12,5 mg tablet) Target dose: 5-7 weeks (25 mg tablet)
干预措施: Hydrochlorthiazide® (Drug)
Repeated treatment X
Each patient receives all four treatments, and in addition repeats two of the treatments, labeled X and Y.
The repeated arms will be given with the same duration and dosing as the other arms.
干预措施: Treatment X (Drug)
Repeated treatment Y
Each patient receives all four treatments, and in addition repeats two of the treatments, labeled X and Y.
The repeated arms will be given with the same duration and dosing as the other arms.
干预措施: Treatment Y (Drug)
Placebo
This is an unblinded placebo run-in which we use to generate baseline values. Each patient will initiate their participation with these 2 weeks of placebo treatment, taking 1 capsule daily.
干预措施: Placebo (Drug)
结局指标
主要结局
Between-person variation in blood pressure-lowering effects of blood pressure-lowering drugs, measured as variation in daytime (10 a.m. to 8 p.m.) ambulatory systolic blood pressure.
时间窗: This outcome will be analysed based on measurements on the last day of each treatment period (week 7-9).
次要结局
- Between-person variation in side effects of blood pressure-lowering drugs, as measured with a modified section of a validated questionnaire about adverse effects of antihypertensive drugs (PERSYVE section 2.1)(This outcome will be analysed based on data collected on the next to last day of each treatment period (week 7-9).)
- Overall patient treatment preferences measured with a questionnaire on paper.(This outcome will be measured on the last visit for each patient, i.e. week 56.)
- The difference in patient treatment preferences between the blood pressure lowering drug classes, as measured with a treatment preference rating questionnaire.(This outcome will be analysed based on data collected on the next to last day of each treatment period (week 7-9).)