Renin-angiotensin-aldosterone System (RAAS), Inflammation, and Post-Operative Atrial Fibrillation (AF)
|ClinicalTrials.gov Identifier: NCT00141778|
Recruitment Status : Completed
First Posted : September 1, 2005
Results First Posted : March 22, 2013
Last Update Posted : March 22, 2013
|Condition or disease||Intervention/treatment||Phase|
|Atrial Fibrillation||Drug: Placebo Drug: Ramipril Drug: Spironolactone||Phase 2 Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||455 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||RAAS, Inflammation, and Post-operative AF|
|Study Start Date :||April 2005|
|Primary Completion Date :||July 2010|
|Study Completion Date :||August 2010|
Placebo Comparator: Placebo
matched placebo pills daily beginning 4-7 days before surgery and continuing through discharge
Matching placebo taken once a day
Other Name: Placebo tablet
Ramipril daily (2.5mg, increased to 5mg) beginning 4 to 7 days before surgery and continuing through discharge
Taken orally, once a day
Other Name: Angiotensin-converting enzyme inhibitor
Spironolactone 25mg daily beginning 4 to 7 days before surgery and continuing through discharge
Taken orally, once a day
Other Name: Mineralocorticoid Receptor Antagonist
- Postoperative Atrial Fibrillation [ Time Frame: 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.
- Acute Renal Failure [ Time Frame: Measured until the time of hospital discharge, from 5.7 to 6.8 days on average, depending on the study group. ]Percentage of patients with a creatinine concentrations >2.5mg/dl
- Hypotension [ Time Frame: Measured during and after surgery, until discharge, from 5.7 to 6.8 days on average. ]Percentage of patients with hypotension defined as a systolic blood pressure <90 mmHg and/or prolonged requirement for vasopressor use.
- Hypokalemia [ Time Frame: Measured until the time of hospital discharge, which was an average of 5.7 to 6.8 days depending on the treatment arm. ]Percentage of patients who had a serum potassium concentrations <3.5 milliequivalents (mEq)/L
- Time to Tracheal Extubation [ Time Frame: It is the time (in minutes) from admission to the ICU until tracheal extubation ]It is the time in minutes that it took to extubate the patient after surgery.
- Length of Hospital Stay (Days) [ Time Frame: Measured from the day of surgery until the time of hospital discharge ]
- Death [ Time Frame: Measured until the time of hospital discharge ]The percentage of patients in each study arm who died.
- Stroke [ Time Frame: Measured until the time of hospital discharge, from 5.7 to 6.8 days on average depending on the study arm. ]Percentage of patients in each study group who experience a cerebrovascular event, confirmed by CT.
- Perioperative Interleukin(IL)-6 Concentrations [ Time Frame: Perioperative period ]Interleukin-6 was measured at several time points (see time points in table) over the course of the study
- Perioperative Plasminogen Activator Inhibitor-1 (PAI-1) Concentrations [ Time Frame: Perioperative period ]Plasminogen activator inhibitor-1 (PAI-1) was measured at several time points (see table) over the course of the study.
- Perioperative C-reactive Protein (CRP) Concentrations [ Time Frame: Perioperative period ]C-reactive protein was measured at several time points (see table) over the course of the study.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00141778
|United States, Tennessee|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||Nancy J. Brown, M.D.||Vanderbilt University|