A Prospective, Randomized, Open-label Clinical Trial on the Effects of Intensive Versus Conventional Control of Ambulatory-determined Asleep Systolic Blood Pressure Mean on Cardiovascular, Metabolic, and Renal Disease Risks
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 5,320
- 试验地点
- 18
- 主要终点
- New-onset type 2 diabetes
研究概览
简要总结
On the basis of new evidence on the relationship between achieved office blood pressure (BP) measurements (OBPM) and the risk of cardiovascular disease (CVD) morbidity and mortality documented in the SPRINT trial, the recent 2017 guidelines of the American College of Cardiology (ACC) and the American Heart Association (AHA) have established lower values of 130/80 mmHg for clinic systolic BP (SBP)/diastolic BP (DBP) as new diagnostic thresholds for hypertension and therapeutic targets for treatment of all individuals aged ≥18 years regardless of age, sex, or concomitant complications including presence of diabetes, chronic kidney disease (CKD), or history of past CVD event. According to these guidelines, the new proposed ambulatory BP measurment (ABPM) thresholds for diagnosis of hypertension in adults are 130/80 and 110/65 mmHg for the awake and asleep SBP/DBP means, respectively. However, the ACC/AHA guidelines do not provide any scientific evidence documenting neither the equivalence between these ABPM thresholds and the 130/80 mmHg cut-off values for OBPM nor the potential improved CVD event-free survival time of the proposed more intensive control of ambulatory BP.
Results derived from observational prospective studies consistently document that therapeutic BP targets in hypertensive individuals, i.e., persons at increased CVD risk, should be established in terms of proper control of asleep BP. To date, no prospective randomized study has ever before evaluated which should be the adequate therapeutic ABPM target for most effective reduction of CVD risk. Accordingly, the Tratamiento de Hipertensión Arterial Durante el Sueño study (THADEUS, i.e., Treatment of Hypertension During Sleep) has been designed to prospectively evaluate if "intensive control" of asleep SBP mean proposed by the new ACC/AHA guidelines (<110 mmHg) in more effective than the so far its "conventional control" (<120 mmHg) to reduce CVD morbidity and mortality in hypertensive individuals.
详细描述
- BACKGROUND AND RATIONALE OF THE STUDY.
1.1. Clinic and ambulatory blood pressure for the diagnosis of hypertension.
The diagnosis of hypertension and all clinical decisions regarding its treatment today are still mainly based only on a limited number of daytime office blood pressure (BP) measurements (OBPM) obtained in the clinic, occasionally supplemented by wake-time self-assessments at home and work. Those casual time-unspecified OBPM disregard the mostly predictable circadian variation in BP. Various circadian rhythms may also significantly affect the pharmacokinetics and pharmacodynamics, both beneficial and adverse effects, of hypertension medications, as extensively documented. Most important, numerous outcome trials and published meta-analyses substantiate the correlation between BP level and risk of target organ injury damage and cardiovascular disease (CVD) events is much stronger for parameters derived from around-the-clock ambulatory BP monitoring (ABPM) than it is for values derived from traditional daytime OBPM. ABPM is a diagnostic tool with the added advantage that allows thorough description and quantification of all aspects of the 24h BP variation.
On the basis of this substantial and indisputable evidence, several international guidelines now propose ambulatory measurements as a requirement to confirm the office diagnosis of hypertension in adults. On the contrary, other guidelines, despite recognizing greater prognostic value of ABPM than OBPM, still recommended the use of the later for diagnosis of hypertension for "historical reasons" unjustified on the light of current available scientific evidence.
1.2. Asleep BP mean as an independent prognostic marker of CVD risk.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Double (Participant, Outcomes Assessor)
盲法说明
Participants unaware of their assigned randomized group. Outcomes evaluated by an independent Events Committee.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women aged ≥18 years.
- •All participants must: (i) have at randomization sleep-time hypertension according to the current ESH/ESC guidelines, i.e., asleep SBP mean ≥120 mmHg;1 (ii) adhere to a routine of daytime activity and nighttime sleep; and (iii) provide their written informed consent to participate into the study.
排除标准
- •History of drug/alcohol abuse within the last two years.
- •Night/shift-work employment.
- •Previous history of a systemic autoimmune disease or AIDS.
- •Evidence of a secondary form of hypertension, including coarctation of the aorta, hyperaldosteronism, renal artery stenosis, or pheochromocytoma
- •CVD disorders (unstable angina pectoris, heart failure, life-threatening arrhythmia, atrial fibrillation, kidney failure, and grade III-IV retinopathy). Previous CVD events will not be exclusionary if full physical and work activities are maintained.
- •Any surgical or medical condition which might alter the absorption, distribution, metabolism, or excretion of any drug, or, at the discretion of the investigator, might place the subject at higher risk from his/her participation in the study, or are likely to prevent the subject from complying with the requirements of the study or completing the trial period.
- •History of malignancy including leukemia and lymphoma (but not basal cell skin cancer), or any other severe, life-threatening disease within the past five years.
- •Inability to communicate and comply with all study requirements.
- •Intolerance to ABPM.
结局指标
主要结局
New-onset type 2 diabetes
时间窗: Median follow-up of 5 years
Development of type 2 diabetes
New-onset CKD
时间窗: Median follow-up of 5 years
Development of chronic kidney disease
Vascular events
时间窗: Median follow-up of 5 years
Rate of cardiovascular events and stroke
次要结局
- Coronary events(Median follow-up of 5 years)
- Cardiac events(Median follow-up of 5 years)
研究者
Ramon C. Hermida
Professor and Director, Bioengineering & Chronobiology Labs.
University of Vigo