Atorvastatin Therapy for the Prevention of Atrial Fibrillation (SToP-AF)

NCT00252967

Last updated date
Study Location
Veteran Administration Medical Center/Emory University
Atlanta, Georgia, 30033, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Atrial Fibrillation, Inflammation
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

- > or = 18 years of age

- Clinical diagnosis-abnormal heart beat known as atrial fibrillation/flutter (ECG documentation)

- Able to swallow pill form of drug

Exclusion Criteria
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


- < 18 years of age


- enrollment in another ongoing trial


- paroxysmal atrial fibrillation


- hemodynamic instability


- atrial fibrillation ablation within 6 months of enrollment


- a contraindication for anticoagulation


- severe valvular heart disease


- presence of single lead implantable cardioverter defibrillator


- unstable angina


- New York Heart Association (NYHA) Class IV heart failure


- hyperthyroidism


- uncontrolled hypertension (blood pressure > 180/100 at rest) on medications


- an illness that would limit life expectancy to less than 1 year


- use of statins within the previous 30 days


- significant coronary artery disease or lipid abnormalities necessitating statin
therapy


- implanted devices for active management of arrhythmias by pacing or defibrillation


- lack of access to a telephone


- illicit drug use


- alcohol abuse


- hypersensitivity to atorvastatin by history


- pregnancy


- sexually active female subjects not on contraception or surgically sterilized


- nursing mothers


- chronic liver disease or abnormal liver function (elevated transaminases 1.5 times the
upper limit of normal [ULN] of laboratory reference range)


- severe renal disease (creatinine > 200 mmol/L)


- inflammatory muscle disease or creatine kinase (CK) > 3 times ULN


- concurrent treatment with cyclosporine, fibrates, or high-dose niacin

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Atrial Fibrillation, InflammationAtorvastatin Therapy for the Prevention of Atrial Fibrillation (SToP-AF)
NCT00252967
  1. Atlanta, Georgia
  2. Atlanta, Georgia
  3. Atlanta, Georgia
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Atorvastatin Therapy for the Prevention of Atrial Fibrillation (SToP-AF)
Official Title  ICMJE Atorvastatin Therapy for the Prevention of Atrial Fibrillation (SToP-AF)
Brief Summary The purpose of this study is to test whether the drug, atorvastatin, will be able to reduce the rate of return of the abnormal beats after using cardioversion. Atorvastatin is a drug approved by the Food and Drug Administration (FDA) for the treatment of high cholesterol but is not approved for preventing abnormal heartbeats. In addition to lowering cholesterol, the drug reduces inflammation. Inflammation seems to help cause atrial fibrillation, a certain type of abnormal heartbeat. In animals, atorvastatin reduces the risk of this type of abnormal beats, and preliminary data in humans supports an effect of atorvastatin and other similar drugs that have the same action on reducing the risk of this type of abnormal beats. We, the researchers at Emory University, would like to learn if this drug could prevent the return of these abnormal heartbeats.
Detailed Description

Atrial fibrillation (AF) and its related disorder, atrial flutter (AFlut), are common abnormal heartbeats. Because they are similar and AFlut is rare compared to AF, they are usually treated similarly and discussed as one disorder. AF is an extremely common arrhythmia affecting more that 5% of the population over 65 years of age. It is an independent risk factor for death. AF is considered a progressive disease increasing in prevalence with age and converting from paroxysmal to permanent within a single individual. The projected lifetime risk of AF is 1 in 4 for men. AF occurs when there is an electrical short circuit in the top parts of the heart (atria). This causes the atria to beat at >300 times per min in an irregular and ineffective manor. This has two consequences. The blood tends to pool in the atria allowing for clotting. Second, the bottom parts of the heart (ventricles) beat too rapidly in response to impulses arising in the atria. The rapid ventricular contraction without adequate filling time results in a reduced ejection of blood. This can cause heart failure symptoms such as shortness of breath and reduced blood flow to organs resulting in lightheadedness or collapse.

One logical therapy to correct the defects arising from AF is return the abnormal heartbeats back to the normal rhythm. This can be done with electrical shock therapy (cardioversion) or by drugs called antiarrhythmic agents. Often, they are used together. While its stands to reason that using these techniques to restore rhythm to normal would be beneficial, clinical trials show that leaving patients in AF and thinning the blood to prevent blood clots is equally efficacious to trying to restore normal beating (sinus rhythm). The common explanations for this are that AF returns rapidly despite antiarrhythmic drugs and that antiarrhythmic drugs can make worse abnormal heart beats, a phenomenon known as proarrhythmia.

Based on the lack of efficacy of current therapies and similarities between risk factors for atherosclerosis (hardening of the arteries) and AF, we began to investigate whether oxidative stress, a mechanism similar to inflammation thought to be responsible for atherosclerosis, might be playing a role in causing AF. We studied this in pigs first and found that when we put pigs into AF, they had a large increase in oxidative stress markers. Then, we made a mouse that had too much oxidative stress in the heart, and this mouse developed AF. Based on this and other data in humans, we hypothesized that oxidative stress can cause AF.

Atorvastatin is a cholesterol lowering medication that works by blocking production of cholesterol at an early stage. This has the effect of preventing the synthesis of molecules required to assemble the most common enzymatic source of oxidative stress, the NADPH oxidase. Therefore, atorvastatin decreases oxidative stress in addition to reducing cholesterol, and if our hypothesis is correct, atorvastatin should reduce the incidence of AF.

In this study we chose to look at patients undergoing cardioversion. This is because this group has a high likelihood of recurrence of AF and would benefit most by an effective drug. Once the decision is made to have the patient undergo cardioversion, we will approach the patient about enrolling in this trial. The only change in their medical therapy will be the addition of the study drug. The study requires no other alterations to the standard of care. If patients agree to participate, then they will be started on the study drug and followed for recurrence of AF by a variety of surface electrocardiogram techniques. All of which are noninvasive. To insure the medicine is not causing side effects, examinations and blood tests will be done, and to study whether the drug actually affects oxidative stress, blood will be analyzed. The subjects participation ends when AF recurs or after 1 year. This will be a double blind, placebo controlled trial and will be analyzed on an intention to treat basis.

The risks of this study to the patient are likely to be small compared to the potential benefit of reduced AF burden. Based on a previous trial using the same dose of study medication, the risks of all study drug related adverse events is likely to be <3%. All of these are expected to be reversible with discontinuation of the drug.

The significance of this research is that currently treatments to address AF are less than optimal. Antiarrhythmic drugs are variably effective and are associated with potentially lethal proarrhythmic side effects. The common treatment to prevent strokes in subjects with AF is chronic warfarin administration, but warfarin therapy requires frequent monitoring and adjustment of dose and is associated with bleeding complications. This research may provide the first new therapeutic strategy in many years for AF and the most serious consequence of AF, stroke.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Prevention
Condition  ICMJE
  • Atrial Fibrillation
  • Inflammation
Intervention  ICMJE
  • Drug: Atorvastatin
    80 mg of Atorvastatin
  • Drug: Placebo
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo taken daily
    Intervention: Drug: Placebo
  • Experimental: Atorvastatin
    Atorvastatin at a dose of 80 mg daily
    Intervention: Drug: Atorvastatin
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: August 21, 2014)
64
Original Enrollment  ICMJE
 (submitted: November 14, 2005)
258
Actual Study Completion Date  ICMJE October 2009
Actual Primary Completion Date November 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • > or = 18 years of age
  • Clinical diagnosis-abnormal heart beat known as atrial fibrillation/flutter (ECG documentation)
  • Able to swallow pill form of drug

Exclusion Criteria:

  • < 18 years of age
  • enrollment in another ongoing trial
  • paroxysmal atrial fibrillation
  • hemodynamic instability
  • atrial fibrillation ablation within 6 months of enrollment
  • a contraindication for anticoagulation
  • severe valvular heart disease
  • presence of single lead implantable cardioverter defibrillator
  • unstable angina
  • New York Heart Association (NYHA) Class IV heart failure
  • hyperthyroidism
  • uncontrolled hypertension (blood pressure > 180/100 at rest) on medications
  • an illness that would limit life expectancy to less than 1 year
  • use of statins within the previous 30 days
  • significant coronary artery disease or lipid abnormalities necessitating statin therapy
  • implanted devices for active management of arrhythmias by pacing or defibrillation
  • lack of access to a telephone
  • illicit drug use
  • alcohol abuse
  • hypersensitivity to atorvastatin by history
  • pregnancy
  • sexually active female subjects not on contraception or surgically sterilized
  • nursing mothers
  • chronic liver disease or abnormal liver function (elevated transaminases 1.5 times the upper limit of normal [ULN] of laboratory reference range)
  • severe renal disease (creatinine > 200 mmol/L)
  • inflammatory muscle disease or creatine kinase (CK) > 3 times ULN
  • concurrent treatment with cyclosporine, fibrates, or high-dose niacin
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00252967
Other Study ID Numbers  ICMJE IRB00024771
1137-2004 ( Other Identifier: Other )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Samuel C. Dudley, Jr., Emory University
Study Sponsor  ICMJE Emory University
Collaborators  ICMJE Pfizer
Investigators  ICMJE
Principal Investigator:Samuel D. Dudley, Jr., MD, PhDUS Department of Veterans Affairs
PRS Account Emory University
Verification Date August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP