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

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

455 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-04-30

Study Completion Date

2010-08-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Impact of Renin-Angiotensin System Inhibitors Continuation on Outcome After Major Surgery

NCT03374449

Renin Angiotensin System Surgery

COMPLETED NA

Combined Renin Inhibition/Beta-blockade

NCT00627861

Hypertension

TERMINATED NA

The Role of Angiotensin Type I Receptor in the Regulation of Human Peripheral Vascular Function

NCT00001628

Atherosclerosis Heart Failure, Congestive Hypertension +1 more

COMPLETED PHASE3

Is Spironolactone Safe and Effective in the Treatment of Cardiovascular Disease in Mild Chronic Renal Failure?

NCT00291720

Chronic Kidney Disease Cardiovascular Disease

COMPLETED PHASE2

The Role of Angiotensin Type I Receptor in the Regulation of Human Coronary Vascular Function

NCT00001629

Atherosclerosis Heart Failure, Congestive Hypertension +1 more

COMPLETED PHASE3

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Atrial Fibrillation

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Placebo

matched placebo pills daily beginning 4-7 days before surgery and continuing through discharge

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Matching placebo taken once a day

Ramipril

Ramipril daily (2.5mg, increased to 5mg) beginning 4 to 7 days before surgery and continuing through discharge

Group Type EXPERIMENTAL

Ramipril

Intervention Type DRUG

Taken orally, once a day

Spironolactone

Spironolactone 25mg daily beginning 4 to 7 days before surgery and continuing through discharge

Group Type EXPERIMENTAL

Spironolactone

Intervention Type DRUG

Taken orally, once a day

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Placebo

Matching placebo taken once a day

Intervention Type DRUG

Ramipril

Taken orally, once a day

Intervention Type DRUG

Spironolactone

Taken orally, once a day

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Placebo tablet Angiotensin-converting enzyme inhibitor Mineralocorticoid Receptor Antagonist

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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

Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No