RAAS, Inflammation, and Post-operative AF
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 455
- 试验地点
- 1
- 主要终点
- Postoperative Atrial Fibrillation
研究概览
简要总结
Atrial fibrillation (AF) is the most prevalent, sustained type of irregular heartbeat and affects over 2 million Americans. Post-operative AF, which leads to significant morbidity and a prolonged hospital stay, complicates 20% to 40% of cardiopulmonary bypass (CPB) surgical procedures. While recent studies indicate that interruption of the renin-angiotensin-aldosterone system by either angiotensin-converting enzyme (ACE) inhibition or AT1 receptor antagonism decreases the incidence of AF following a heart attack or cardioversion (electric shock to the heart), its effect on the incidence of post-operative AF has not been throughly studied. Studies in both animals and humans suggest that inflammation-induced atrial remodeling plays an important role in the cause of AF. Recent studies also provide evidence that activation of the renin-angiotensin-aldosterone system induces inflammation, myocyte injury, proarrhythmic electrical remodeling, and fibrosis through aldosterone.
详细描述
AF is the most prevalent, sustained type of irregular heartbeat and affects over 2 million Americans. Post-operative atrial fibrillation(AF), which leads to significant morbidity and a prolonged hospital stay, complicates 20% to 40% of CPB surgical procedures. While recent studies indicate that interruption of the renin-angiotensin-aldosterone system by either angiotensin-converting enzyme(ACE) inhibition or angiotensin II subtype 1 (AT1) receptor antagonism decreases the incidence of AF following a heart attack or cardioversion (electric shock to the heart), its effect on the incidence of post-operative AF has not been throughly studied. Studies in both animals and humans suggest that inflammation-induced atrial remodeling plays an important role in the cause of AF. Recent studies also provide evidence that activation of the renin-angiotensin-aldosterone system induces inflammation, myocyte injury, proarrhythmic electrical remodeling, and fibrosis through aldosterone.
This study will evaluate the effectiveness of ACE inhibition and aldosterone receptor antagonism at decreasing inflammation and AF following cardiopulmonary bypass (CPB) surgery.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Undergoing elective valvular heart surgery, coronary artery bypass grafting
- •If female, must be postmenopausal for at least 1 year, status-post surgical sterilization, or if of childbearing potential, utilizing adequate birth control and willing to undergo urine beta-hcg testing prior to drug treatment and throughout the study
- •Exclusion Criteria
- •History of AF other than remote paroxysmal AF
- •Ejection fraction less than 30%
- •Evidence of coagulopathy (INR greater than 1.7 without warfarin therapy)
- •Emergency surgery
- •History of ACE inhibitor-induced angioedema
- •Low blood pressure (systolic blood pressure less than 100 mmHg and evidence of hypoperfusion)
- •Hyperkalemia (potassium level greater than 5.0 milliequivalents (mEq)/L at study entry)
- •Impaired kidney function (serum creatinine level greater than 1.6 mg/dl)
- •Any underlying or acute disease requiring regular medication that could possibly cause complications or make implementation of the study or interpretation of the study results difficult
- •Inability to discontinue current ACE inhibitor, AT1 receptor antagonist, or aldosterone receptor antagonist therapy
- •History of alcohol or drug abuse
- •Treatment with any investigational drug in the month prior to study entry
- •Mental condition that makes it impossible to understand the nature, scope and possible consequences of the study
- •Inability to comply with the study procedures (e.g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study)
- •Pregnant or breastfeeding
排除标准
- 未提供
研究组 & 干预措施
Spironolactone
Spironolactone 25mg daily beginning 4 to 7 days before surgery and continuing through discharge
干预措施: Spironolactone (Drug)
Placebo
matched placebo pills daily beginning 4-7 days before surgery and continuing through discharge
干预措施: Placebo (Drug)
Ramipril
Ramipril daily (2.5mg, increased to 5mg) beginning 4 to 7 days before surgery and continuing through discharge
干预措施: Ramipril (Drug)
结局指标
主要结局
Postoperative Atrial Fibrillation
时间窗: Measured from admission to the ICU until discharge from hospital
The primary endpoint of the study was the percentage of patients with electrocardiographically confirmed AF of at least 10 secs duration at any time following the end of surgery until hospital discharge, an average from 5.7 days in the ramipril group to 6.8 days in the placebo group. Patients were monitored continuously on telemetry throughout the postoperative period until discharge. Electrocardiograms were obtained for any rhythm changes detected on telemetry monitoring, and in addition, electrocardiograms were performed preoperatively, at admission to the intensive care unit, and daily starting on postoperative day 1. All electrocardiograms and rhythm strips were reviewed in a blinded fashion by a single cardiac electrophysiologist.
次要结局
- Acute Renal Failure(Measured until the time of hospital discharge, from 5.7 to 6.8 days on average, depending on the study group.)
- Hypotension(Measured during and after surgery, until discharge, from 5.7 to 6.8 days on average.)
- Hypokalemia(Measured until the time of hospital discharge, which was an average of 5.7 to 6.8 days depending on the treatment arm.)
- Time to Tracheal Extubation(It is the time (in minutes) from admission to the ICU until tracheal extubation)
- Length of Hospital Stay (Days)(Measured from the day of surgery until the time of hospital discharge)
- Death(Measured until the time of hospital discharge)
- Stroke(Measured until the time of hospital discharge, from 5.7 to 6.8 days on average depending on the study arm.)
- Perioperative Interleukin(IL)-6 Concentrations(Perioperative period)
- Perioperative Plasminogen Activator Inhibitor-1 (PAI-1) Concentrations(Perioperative period)
- Perioperative C-reactive Protein (CRP) Concentrations(Perioperative period)
研究者
Nancy J. Brown
Professor of Medicine and Pharmacology
Vanderbilt University