Comparison of Two Treatments to Decrease Inflammation and Atrial Fibrillation Following Cardiopulmonary Bypass Surgery

Condition(s) targeted: Cardiovascular Diseases; Heart Diseases; Arrhythmia

Intervention: Ramipril (Drug); Spironolactone (Drug); Placebo (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: National Heart, Lung, and Blood Institute (NHLBI)

Official(s) and/or principal investigator(s):
Nancy J. Brown, MD, Principal Investigator, Affiliation: Vanderbilt University

The purpose of this study is to test the hypothesis that aceytl cholinesterase (ACE) inhibition or aldosterone receptor antagonism will decrease inflammation and atrial fibrillation (AF) following cardiopulmonary bypass (CPB) surgery.

Official title: Renin-Angiotensin-Aldosterone System (RAAS), Inflammation, and Post-Operative Atrial Fibrillation

Study design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: Occurrence of electrocardiographically confirmed AF or flutter at any time following neutralization of heparin at the end of CPB

Secondary outcome:

Intra-operative MAP

Intra-operative and post-operative requirements for pressors

Death

Length of hospital stay

Post-operative IL-6, PAI-1, t-PA and CRP concentrations and other biomarkers

Serum potassium concentrations

Creatinine concentrations (measured throughout participant's hospital stay)

Stroke

Detailed description: BACKGROUND:

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 CPB surgical procedures. While recent studies indicate that interruption of the renin-angiotensin-aldosterone system by either ACE inhibition or AT1 receptor antagonism decreases the incidence of AF following a heart attack or cardioversion (an 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.

DESIGN NARRATIVE:

This study will evaluate the effectiveness of ACE inhibition and aldosterone receptor antagonism at decreasing inflammation and AF following CPB surgery.

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Undergoing elective valvular heart surgery, coronary artery bypass grafting, including

surgery requiring CPB

- 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 mm Hg and evidence of

hypoperfusion)

- Hyperkalemia (potassium level greater than 5. 0 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

Vanderbilt University Medical Center, Nashville, Tennessee 37232, United States; Recruiting
Nancy J. Brown, MD, Phone: 615-343-8701, Email: NANCY.J.BROWN@VANDERBILT.EDU
Nancy J. Brown, MD, Principal Investigator

Starting date: April 2005
Ending date: December 2010
Last updated: December 13, 2007