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Renin-angiotensin-aldosterone System (RAAS), Inflammation, and Post-Operative Atrial Fibrillation (AF)

Information source: Vanderbilt University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Atrial Fibrillation

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

Phase: Phase 2/Phase 3

Status: Completed

Sponsored by: Vanderbilt University

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

Summary

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.

Clinical Details

Official title: RAAS, Inflammation, and Post-operative AF

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Primary outcome: Postoperative Atrial Fibrillation

Secondary outcome:

Acute Renal Failure

Hypotension

Hypokalemia

Time to Tracheal Extubation

Length of Hospital Stay (Days)

Death

Stroke

Perioperative Interleukin(IL)-6 Concentrations

Perioperative Plasminogen Activator Inhibitor-1 (PAI-1) Concentrations

Perioperative C-reactive Protein (CRP) Concentrations

Detailed description: 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.

Eligibility

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

Criteria:

Inclusion Criteria: 1. Undergoing elective valvular heart surgery, coronary artery bypass grafting 2. 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 1. History of AF other than remote paroxysmal AF 2. Ejection fraction less than 30% 3. Evidence of coagulopathy (INR greater than 1. 7 without warfarin therapy) 4. Emergency surgery 5. History of ACE inhibitor-induced angioedema 6. Low blood pressure (systolic blood pressure less than 100 mmHg and evidence of hypoperfusion) 7. Hyperkalemia (potassium level greater than 5. 0 milliequivalents (mEq)/L at study entry) 8. Impaired kidney function (serum creatinine level greater than 1. 6 mg/dl) 9. 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 10. Inability to discontinue current ACE inhibitor, AT1 receptor antagonist, or aldosterone receptor antagonist therapy 11. History of alcohol or drug abuse 12. Treatment with any investigational drug in the month prior to study entry 13. Mental condition that makes it impossible to understand the nature, scope and possible consequences of the study 14. Inability to comply with the study procedures (e. g., uncooperative attitude, inability to return for follow-up visits, and unlikelihood of completing the study) 15. Pregnant or breastfeeding

Locations and Contacts

Vanderbilt University, Nashville, Tennessee 37232, United States
Additional Information

Starting date: April 2005
Last updated: February 19, 2013

Page last updated: August 23, 2015

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