A Prospective Randomised Open- Label Blinded-Endpoint (PROBE) Trial Comparing Telmisartan (MICARDIS®) (40-80-80mg QD) and Ramipril (2.5-5--10mg QD) in Patients With Mild-to-Moderate Hypertension Using Ambulatory Blood Pressure Monitoring. PRISMA = Prospective Randomised Investigation of the Safety and Efficacy of Micardis® vs Ramipril Using ABPM
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 801
- 试验地点
- 81
- 主要终点
- Changes in the last 6-hour mean (relative to dose time) diastolic and systolic blood pressure (DBP and SBP) as measured by ABPM
研究概览
简要总结
The primary objective of this study is to demonstrate that telmisartan 80 mg (MICARDIS®) is at least as effective and possibly superior to ramipril 5mg and 10mg in lowering mean ambulatory diastolic blood pressure (DBP) and systolic blood pressure (SBP) during the last 6 hours of the 24-hour dosing interval in mild-to-moderate hypertensive patients at the end of an 8 and 14-week treatment period, respectively.
详细描述
Secondary objectives will compare telmisartan (80 mg) (MICARDIS® and ramipril (5 mg and 10 mg) on: 1) the reduction in the last 6-hour ABPM mean pulse pressure (PP) relative to dosing, 2) the reductions in the 24-hour ABPM mean DBP, SBP and PP relative to dosing, 3) reductions in ABPM mean DBP, SBP and PP during other periods of the 24-hour dosing interval (i.e., morning, daytime, and nighttime) relative to clock time, 4) change from baseline in systolic and diastolic blood pressure load during the 24-hour dosing interval, 5) reductions in the mean seated trough DBP and SBP measured using a manual in-clinic cuff sphygmomanometer, 6) responder rates as determined by both ABPM and manual in-clinic cuff measurements and 7) Health-Related Quality of Life (HRQL).
Study Hypothesis:
It is hypothesised that the rise of blood pressure (BP) during the last hours of the sleeping period is a cause of the high incidence of cardiovascular events in the morning. The purpose of the present study is to demonstrate that telmisartan (MICARDIS®) is not inferior to ramipril in lowering blood pressure in patients with mild-to-moderate hypertension. Blood pressure will be assessed by ambulatory blood pressure monitoring (ABPM) as this will allow comparison of the full 24-hour effects of both treatments without artefacts (e.g., white-coat hypertension) introduced by measurement of blood pressure in the clinic. This will measure diastolic blood pressures over the entire 24-hour dosing interval, with primary attention focused on the last six hours of the dosing interval.
NULL AND ALTERNATIVE HYPOTHESES In order to test the multiple hypotheses (e.g., non-inferiority and superiority of telmisartan compared to ramipril), multiple dosages (i.e., telmisartan 80mg (MICARDIS®) versus ramipril 5mg and ramipril 10mg after 8 and 14 weeks of treatment, respectively), and the two endpoints (i.e., reduction in DBP and SBP during the last 6 hours of the 24-hour dosing interval) as measured by ABPM, a completely hierarchical, closed testing procedure will be used.
Hierarchical Closed Testing Procedure:
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
- Double
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
- •Mild-to-moderate hypertension defined as a mean seated diastolic blood pressure of greater than or equal to 95 mmHg and less than or equal to 109 mmHg, measured by manual cuff sphygmomanometer at Visit
- •24-hour mean DBP of greater than or equal to 85 mmHg at Visit 3 as measured by ABPM.
- •Age 18 years or older.
- •Ability to stop any current antihypertensive therapy without risk to the patient (investigator's discretion).
- •Ability to provide written informed consent in accordance with GCP and local legislation.
排除标准
- •Pre-menopausal women (last menstruation approximately less than or equal to 1 year prior to signing informed consent) who:
- •Are not surgically sterile
- •Are nursing,
- •Are of child-bearing potential and are NOT practicing acceptable methods of birth control, or do NOT plan to continue practicing an acceptable method throughout the study. Acceptable methods of birth control include intra uterine device, oral, implantable or injectable contraceptives.
- •Night shift workers who routinely sleep during the daytime and whose work hours include midnight to 4:00 A.M.
- •Mean sitting SBP greater than or equal to180 mmHg or mean sitting DBP greater than or equal to 110 mmHg during any visit of the placebo run-in period.
- •Known or suspected secondary hypertension (i.e., pheochromocytoma).
- •Hepatic and/or renal dysfunction as defined by the following laboratory parameters:
- •SGPT (ALT) or SGOT (AST) > 2 times the upper limit of normal range.
- •Serum creatinine > 2.3mg/dL (or > 203 micromol/l).
- •Bilateral renal artery stenosis, renal artery stenosis in a solitary kidney, post-renal transplant patients or patients with only one kidney.
- •Clinically relevant sodium depletion, hypokalaemia or hyperkalaemia.
- •Uncorrected volume depletion.
- •Primary aldosteronism.
- •Hereditary fructose intolerance.
- •Biliary obstructive disorders.
- •Congestive heart failure (NYHA functional class CHF III-IV).
- •Unstable angina within the past three months prior to start of run in period.
- •Stroke within the past six months prior to start of run in period.
- •Myocardial infarction or cardiac surgery within the past three months prior to start of run in period.
- •PTCA (percutaneous transluminal coronary angioplasty) within the past three months prior to start of run in period.
- •Sustained ventricular tachycardia, atrial fibrillation, atrial flutter or other clinically relevant cardiac arrhythmias as determined by the investigator.
- •Hypertrophic obstructive cardiomyopathy, aortic stenosis, haemodynamically relevant stenosis of the aortic or mitral valve.
- •Patients with insulin-dependent diabetes mellitus whose diabetes has not been stable and controlled for at least the past three months as defined by an HbA1C greater than or equal to 10%.
- •Patients who have previously experienced symptoms characteristic of angioedema during treatment with ACE inhibitors or angiotensin II receptor antagonists.
- •History of drug or alcohol dependency within 6 months prior to start of run in period.
- •Concomitant administration of any medications known to affect blood pressure, except medication allowed by the protocol.
- •Any investigational therapy within one month of start of run in period.
- •Known hypersensitivity to any component of the formulations.
- •Any clinical condition which, in the opinion of the investigator would not allow safe completion of the protocol and safe administration of trial medication.
- •Inability to comply with the protocol.
结局指标
主要结局
Changes in the last 6-hour mean (relative to dose time) diastolic and systolic blood pressure (DBP and SBP) as measured by ABPM
时间窗: after 8 and 14 weeks
次要结局
- Changes in the ABPM mean (relative to clock-time) for DBP, SBP and PP during the morning, daytime and night-time periods of the 24-hour dosing interval.(after 8 and 14 weeks)
- Manually triggered BP measurements before going to bed and upon arising in the morning(after 8 and 14 weeks)
- Changes in the 24-hour ABPM mean (relative to dosing time) for DBP, SBP and PP(after 8 and 14 weeks)
- Changes from baseline in patient Health Related Quality of Life (HRQL) as measured by Psychological General Wellbeing Index (PGWB).(week 8 and 14)
- Incidence of adverse events(up to 14 weeks)
- Changes in the last 6-hour ABPM mean (relative to dosing time) for pulse pressure (PP)(after 8 and 14 weeks)
- Changes in SBP and DBP load during the 24-hour dosing interval(after 8 and 14 weeks)
- Changes in mean seated trough DBP and SBP as measured by manual in-clinic cuff sphygmomanometer(after 8 and 14 weeks)
- Responder rates based on both the 24-hour ABPM mean (relative to dose time) BPs and manual in-clinic trough cuff measurements(after 8 and 14 weeks)