Ambulatory 24-Hour Cardiac Oxygen Consumption and Blood Pressure-Heart Rate Variability: Effects of Nebivolol and Valsartan Alone and in Combination
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 26
- 试验地点
- 1
- 主要终点
- ACRPP: 24-hour Ambulatory Central Rate-pressure Product (Also Called TTI, CTTI)
研究概览
简要总结
A randomized,double-blind, active controlled,15 week study to evaluate the effects of nebivolol and valsartan alone and in combination on 24-hour ambulatory cardiac work and variability of heart rate-mean central systolic pressure product.
详细描述
Subjects with hypertension (systolic blood pressure (SBP) >140 or diastolic blood pressure (DBP)>90, n=26) were studied using a double-blinded, forced-titration, sequence-controlled, crossover design with 3 experimental periods: Valsartan 320, nebivolol 40, and nebivolol/valsartan 320/40 mg daily. After 4 weeks of each drug, ambulatory pulse wave analysis (IEM MobilOGraph) was performed every 20 min for 24-hours. The primary hypothesis was that nebivolol/valsartan combination therapy would be superior to valsartan monotherapy in reducing mean 24-hour mean myocardial oxygen consumption determined by 24-hour ambulatory heart rate-central systolic pressure product [ACRPP]. A secondary hypothesis was that the combination would also reduce the variability of 24-hour myocardial oxygen consumption.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
Double-blinded: drugs formulated into capsules by an outside research pharmacist who held the codes until study completion
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
- •Subjects with chronic hypertension, treated or untreated
- •Males and females, 18 years or older
- •Seated clinic systolic BP 145-184 mmHg inclusive or
- •Seated clinic diastolic BP 92-119 mmHg, inclusive.
排除标准
- •Subjects with any of the following conditions will be excluded:
- •Any acute or chronic medical condition that, in the judgment of the investigator, renders the subject unable to complete the study, would interfere with optimal participation in the study, or cause significant risk to the subject
- •Concomitant or probable need for treatment with other cardiovascular or antihypertensive drugs that may affect blood pressure or influence the effects of study drugs, (e.g. NSAIDs, beta-agonist inhalers therapy for bronchospastic asthma, diuretics); other stable chronic medications that have little effect on study drugs (e.g. diabetes medications, hormone replacements, chronic pain medications. osteoporosis drugs, vitamins, cholesterol drugs, etc.) are permitted if continued at stable doses throughout study.
- •History of clinically significant adverse events with beta-blocker or angiotensin-receptor blocker
- •Known or suspected secondary hypertension (e.g., renovascular hypertension, primary hyperaldosteronism, etc.)
- •Known ischemic heart disease requiring continuous beta-blocker therapy (includes angina, prior transmural myocardial infarction, coronary artery bypass graft surgery or percutaneous transluminal coronary angioplasty or stenting within 6 months prior to study entry).
- •Dilated cardiomyopathy (NYHA Functional Class III-IV)
- •Clinically significant valvular heart disease or obstructive hypertrophic cardiomyopathy
- •Presence of clinically significant ventricular or supraventricular arrhythmias (e.g. atrial fibrillation/flutter), pre-excitation syndrome, second or third degree atrioventricular block, other conduction defects necessitating the implantation of a permanent cardiac pacemaker, or sick sinus syndrome.
- •Chronic kidney disease (serum creatinine >2.5 mg/dL)
- •Uncontrolled diabetes mellitus (hemoglobin A1c > 10%)
- •History of alcohol or other drug abuse within 6 months prior to enrollment
- •Positive pregnancy test or failure to practice adequate contraception in women of child-bearing potential
研究组 & 干预措施
Sequence 1: Nebivolol first, then valsartan, then combination of nebivolol/valsartan
Nebivolol, 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily; then Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily; then Combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily
干预措施: Nebivolol (Drug)
Sequence 1: Nebivolol first, then valsartan, then combination of nebivolol/valsartan
Nebivolol, 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily; then Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily; then Combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily
干预措施: Valsartan (Drug)
Sequence 1: Nebivolol first, then valsartan, then combination of nebivolol/valsartan
Nebivolol, 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily; then Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily; then Combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily
干预措施: Nebivolol/valsartan combination (Drug)
Sequence 2: Nebivolol first, then combination of nebivolol/valsartan; then valsartan
Nebivolol, 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily; then combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily; then Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily
干预措施: Nebivolol (Drug)
Sequence 2: Nebivolol first, then combination of nebivolol/valsartan; then valsartan
Nebivolol, 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily; then combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily; then Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily
干预措施: Valsartan (Drug)
Sequence 2: Nebivolol first, then combination of nebivolol/valsartan; then valsartan
Nebivolol, 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily; then combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily; then Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily
干预措施: Nebivolol/valsartan combination (Drug)
Sequence 3: Valsartan first, then Nebivolol, then combination of nebivolol/valsartan,
Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily; then Nebivolol, 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily; then combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily;
干预措施: Nebivolol (Drug)
Sequence 3: Valsartan first, then Nebivolol, then combination of nebivolol/valsartan,
Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily; then Nebivolol, 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily; then combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily;
干预措施: Valsartan (Drug)
Sequence 3: Valsartan first, then Nebivolol, then combination of nebivolol/valsartan,
Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily; then Nebivolol, 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily; then combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily;
干预措施: Nebivolol/valsartan combination (Drug)
Sequence 4: Valsartan first, then combination of nebivolol/valsartan, then Nebivolol,
Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily; then combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily; then Nebivolol, 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily;
干预措施: Nebivolol (Drug)
Sequence 4: Valsartan first, then combination of nebivolol/valsartan, then Nebivolol,
Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily; then combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily; then Nebivolol, 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily;
干预措施: Valsartan (Drug)
Sequence 4: Valsartan first, then combination of nebivolol/valsartan, then Nebivolol,
Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily; then combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily; then Nebivolol, 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily;
干预措施: Nebivolol/valsartan combination (Drug)
Sequence 5: Combination of nebivolol/valsartan first, then Nebivolol, then Valsartan,
Combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily; then Nebivolol, 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily; then Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily;
干预措施: Nebivolol (Drug)
Sequence 5: Combination of nebivolol/valsartan first, then Nebivolol, then Valsartan,
Combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily; then Nebivolol, 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily; then Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily;
干预措施: Valsartan (Drug)
Sequence 5: Combination of nebivolol/valsartan first, then Nebivolol, then Valsartan,
Combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily; then Nebivolol, 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily; then Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily;
干预措施: Nebivolol/valsartan combination (Drug)
Sequence 6: Combination of nebivolol/valsartan first, then Valsartan, then Nebivolol, ,
Combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily; then Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily; then Nebivolol, 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily; then
干预措施: Nebivolol (Drug)
Sequence 6: Combination of nebivolol/valsartan first, then Valsartan, then Nebivolol, ,
Combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily; then Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily; then Nebivolol, 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily; then
干预措施: Valsartan (Drug)
Sequence 6: Combination of nebivolol/valsartan first, then Valsartan, then Nebivolol, ,
Combination of nebivolol/valsartan 20/160 mg daily for 1 week followed by 40/320 mg daily for 3 weeks, followed by 1-week down-titration to 20/160 mg daily; then Valsartan, 160 mg daily for 1 week followed by 320 mg daily for 3 weeks, followed by 1-week down-titration to 160 mg daily; then Nebivolol, 20 mg daily for 1 week followed by 40 mg daily for 3 weeks, followed by 1 week down-titration to 20 mg daily; then
干预措施: Nebivolol/valsartan combination (Drug)
结局指标
主要结局
ACRPP: 24-hour Ambulatory Central Rate-pressure Product (Also Called TTI, CTTI)
时间窗: measurement after 4 weeks in each treatment arm
ACRPP is the product of estimated aortic mean systolic pressure (mean aortic pressure estimated using a transfer function applied to brachial cuff blood pressure) during the systolic time interval adjusted for heart rate. Units are (mmHg\*beats/min).
次要结局
- Ambulatory Mean Heart Rate(After 4 weeks in each treatment arm)
- Cuff SBP(After 4 weeks in each treatment arm)
- Cuff DBP(After 4 weeks in each treatment arm)
- Ambulatory Brachial Double Product(After 4 weeks in each treatment arm)
- Nighttime Brachial Diastolic Pressure(After 4 weeks in each treatment arm)
- Ambulatory Mean Central Diastolic BP(After 4 weeks in each treatment arm)
- 24-hour Brachial Systolic BP(4 weeks)
- 24-hour Brachial Diastolic BP(After 4 weeks in each treatment arm)
- Daytime ACRPP (Ambulatory Central Rate-Pressure Product (Also Called TTI, CTTI)(After 4 weeks in each treatment arm)
- Nighttime ACRPP(After 4 weeks in each treatment arm)
- Daytime Heart Rate(After 4 weeks in each treatment arm)
- Nighttime Central Diastolic Pressure(After 4 weeks in each treatment arm)
- Nighttime Heart Rate(4 weeks)
- Nighttime Central Systolic Pressure(4 weeks)
- Daytime Central Systolic Pressure(After 4 weeks in each treatment arm)
- Daytime Brachial Systolic Pressure(After 4 weeks in each treatment arm)
- Nighttime Brachial Systolic Pressure(4 weeks)
- Daytime Brachial Diastolic Pressure(4 weeks)
- Ambulatory Daytime Brachial Rate-pressure Product(After 4 weeks in each treatment arm)
- Daytime Central Diastolic Pressure(4 weeks)
- Ambulatory Nighttime Brachial Rate-pressure Product(After 4 weeks in each treatment arm)
研究者
JOSEPH IZZO
Principal Investigator
State University of New York at Buffalo