The Effects of Renin Inhibition on Fibrinolytic Balance and Endothelial Function
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Difference in Mean Plasma PAI-1 Level
研究概览
简要总结
Aliskiren (also called TekturnaTM) is a new drug for high blood pressure. Aliskiren works by blocking the actions of a substance called renin. Renin is a natural substance in the body that raises blood pressure. Renin is believed to contribute to the production of blood clots by increasing the amount of a substance known as Plasminogen Activator Inhibitor or PAI-1. This study will measure how aliskiren changes the amount of PAI-1 in the blood depending on the time of dosing. The purpose of this study is to find out if it is better to take aliskiren in the morning or at night.
详细描述
Qualifying subjects will be withdrawn from RAAS blockers in a stepwise fashion over one to two weeks. All other blood pressure medications will be continued. If the subject's blood pressure rises above SBP > 170 or DBP > 120 at any time during the study, they will be excluded and the subject will restart their home medication(s).
Week Two - Visit 2 - Post-taper visit: will be issued hydrochlorothiazide (25mg po, qd x 18 weeks, open label). All study medications will be taken daily between 7 and 10 AM. PAI-1 blood sample will be drawn. Pre-menopausal women will schedule this visit for when they have began their cycle.
Week Four- Visit 3 - If their BP (> 120/60 mmHg), potassium (≤ 5.5 meq/dl) and renal function permit (Cr ≤ 1.5 mg/dl), they will be randomized to aliskiren (150 mg po, qd x 2 weeks) or placebo. If applicable, a urine pregnancy test will be done for child bearing age females.
Week Six - Visit 4 - Titration visit: Subjects will return to the GCRC for an interval history, pill count, blood pressure check, and basic metabolic panel. If their BP, potassium and renal function permit, the medication will be increased to aliskiren (300 mg po, qd x 4 weeks) or placebo (double dose). If applicable, a urine pregnancy test will be done for child bearing age females.
Week Eight - Visit 5 - Post-Titration visit: Subjects will return to the GCRC for an interval history, pill count, blood pressure check and basic metabolic panel. If their BP, potassium and renal function permit, they will remain on the current dose of aliskiren.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Diagnostic
- 盲法
- Single (Participant)
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
- •Adults 18-65 with hypertension
- •Hypertension is defined as a systolic blood pressure at screening of ≥ 140, a diastolic blood pressure of ≥ 90, or a preexisting diagnosis of hypertension taking antihypertensive medication. If the subject is on anti-hypertensive medication, they can be included in the study, independent of the screening blood pressure.
排除标准
- •Serum potassium > 5.0 mmol/L (at the visit directly preceding Randomization)
- •History of any cardiovascular event (stroke, TIA, MI, unstable angina, CABG, percutaneous coronary intervention, hospitalization due to HF) during the 3 months prior to Visit 1 or subsequent to enrollment.
- •Malignant Hypertension (at Randomization): any patient with SBP > 170 mmHg or DBP > 120 mmHg
- •Congestive heart failure NYHA class III and IV
- •Unstable serum creatinine
- •Second (II) or third (III) degree heart block without a pacemaker.
- •Concurrent potentially life threatening arrhythmia or other uncontrolled arrhythmia.
- •Clinically significant valvular heart disease.
- •Known renal artery stenosis.
- •Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of the study drugs including, but not limited to, any of the following:
- •History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection (patients with previous bariatric surgery > 6 months prior to Visit 1 are allowed to participate).
- •Any history of pancreatic injury, pancreatitis or evidence of impaired pancreatic function/injury as indicated by abnormal lipase or amylase.
- •Evidence of hepatic disease as determined by any one of the following: SGPT value exceeding 3 x Upper Limit of Normal (ULN) at Visit 1, a history of hepatic encephalopathy, a history of cirrhosis, esophageal varices, or a history of portocaval shunt.
- •History of malignancy other than basal cell skin cancer within the past five years.
- •Any concurrent life threatening condition with a life expectancy less than 2 years.
- •History or evidence of drug or alcohol abuse within the last 12 months.
- •Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study.
- •History of hypersensitivity to any of the study drugs or to medications belonging to the same therapeutic class as the study drugs as well as known or suspected contraindications to the study drugs.
- •History of noncompliance to medical regimens or unwillingness to comply with the study protocol.
- •Use of other investigational drugs at the time of enrollment, or within 30 days or 5 half-lives of enrollment, whichever is longer
- •Any condition that in the opinion of the investigator would jeopardize the evaluation of efficacy or safety.
- •Persons directly involved in the execution of this protocol.
- •Pregnant or nursing (lactating) women
- •Transmeridian travel in the past 6 months
- •Screening physical and lab findings consistent with the AHA/ADA metabolic syndrome criteria (3 of the following: BP ≥ 130/85 or on antihypertensive medications, waist size > 40" (m) > 35" (f), Fasting Glucose ≥ 100 mg/dl, Triglycerides ≥ 150 mg/dl, HDL <40 mg/dl (m) <50 mg/dl (f))
研究组 & 干预措施
HCTZ plus Aliskiren then HCTZ and Placebo
HCTZ 25 mg plus Aliskiren 150mg for 2weeks. Aliskiren is increased to 300mg for 4 week if 150mg was tolerated.
Then HCTZ 25 mg po plus Placebo
干预措施: Aliskiren 150 mg (Drug)
HCTZ plus Aliskiren then HCTZ and Placebo
HCTZ 25 mg plus Aliskiren 150mg for 2weeks. Aliskiren is increased to 300mg for 4 week if 150mg was tolerated.
Then HCTZ 25 mg po plus Placebo
干预措施: Placebo (Drug)
HCTZ plus Aliskiren then HCTZ and Placebo
HCTZ 25 mg plus Aliskiren 150mg for 2weeks. Aliskiren is increased to 300mg for 4 week if 150mg was tolerated.
Then HCTZ 25 mg po plus Placebo
干预措施: HCTZ (Drug)
HCTZ plus Aliskiren then HCTZ and Placebo
HCTZ 25 mg plus Aliskiren 150mg for 2weeks. Aliskiren is increased to 300mg for 4 week if 150mg was tolerated.
Then HCTZ 25 mg po plus Placebo
干预措施: Aliskiren 300 mg (Drug)
HCTZ and Placebo, then HCTZ and Aliskiren
HCTZ 25 mg po plus Placebo.
Then HCTZ 25 mg plus Aliskiren 150mg for 2weeks. Aliskiren is increased to 300mg for 4 week if 150mg was tolerated.
干预措施: Aliskiren 150 mg (Drug)
HCTZ and Placebo, then HCTZ and Aliskiren
HCTZ 25 mg po plus Placebo.
Then HCTZ 25 mg plus Aliskiren 150mg for 2weeks. Aliskiren is increased to 300mg for 4 week if 150mg was tolerated.
干预措施: Placebo (Drug)
HCTZ and Placebo, then HCTZ and Aliskiren
HCTZ 25 mg po plus Placebo.
Then HCTZ 25 mg plus Aliskiren 150mg for 2weeks. Aliskiren is increased to 300mg for 4 week if 150mg was tolerated.
干预措施: HCTZ (Drug)
HCTZ and Placebo, then HCTZ and Aliskiren
HCTZ 25 mg po plus Placebo.
Then HCTZ 25 mg plus Aliskiren 150mg for 2weeks. Aliskiren is increased to 300mg for 4 week if 150mg was tolerated.
干预措施: Aliskiren 300 mg (Drug)
结局指标
主要结局
Difference in Mean Plasma PAI-1 Level
时间窗: baseline to 18 weeks
Difference in Peak Plasma PAI-1 Level
时间窗: baseline to 18 weeks
次要结局
- Difference in Mean Plasma Aldosterone Levels(baseline to 18 weeks)
- Difference in Mean Changes in Plasma Renin Activity.(baseline to 18 weeks)
- Difference in Mean Plasma Peak Aldosterone Levels(baseline to 18 weeks)
研究者
James Muldowney
Assistant Director
Vanderbilt University Medical Center