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Atrial FibrillationPhase 3SOARNCT01182376

SOAR: Study Observing Antiarrhythmic Remodelling Using LGE-MRI

A Phase 3 study testing dronedarone in people with Atrial Fibrillation, run by University of Utah.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The primary objective of this study is to demonstrate how dronedarone (Multaq®) may aid in the slowing of progression of left atrial and ventricular fibrosis in patients with atrial fibrillation as assessed by late gadolinium enhanced magnetic resonance imaging. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Atrial Fibrillation
What is being tested?
dronedarone
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
33 participants
Where
No sites listed yet
Study dates
Nov 2010to Dec 2012
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients age 18 and older
  • Must carry a diagnosis of Paroxysmal Atrial Fibrillation for 1 months or longer prior to being enrolled.
  • AAD: Multaq® (dronedarone) candidate
  • Patients have given informed consent

Who cannot join

  • Patients who are unavailable to continue follow-up at the University of Utah outpatient clinic.
  • Patients weighing >200 lbs (MR image efficacy decreases due to density)
  • Prior RF Ablation treatment for atrial fibrillation
  • Severe renal failure manifested by a chronic GFR of < 30 mL/min, or acute renal failure regardless of the GFR, until the renal function has stabilized. (Gadolinium contraindication)
  • Enrollment in any other investigational trial for anti-arrhythmic therapy
  • Any health related Gadolinium/MRI contraindications: Pacemaker devices, etc.
Show all 18Show fewer
  • Pregnant women
  • Individuals with cognitive impairments who are unable to give informed consent
  • Multaq® (dronedarone) contraindications:
  • NYHA Class IV heart failure or NYHA Class II - III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic
  • Second- or third-degree atrioventricular (AV) block or sick sinus syndrome
  • Bradycardia < 50 bpm
  • Concomitant use of strong CYP 3A inhibitors, such as ketoconazole, itraconazole, voriconazole, cyclosporine, telithromycin, clarithromycin, nefazodone, and ritonavir
  • Concomitant use of drugs or herbal products that prolong the QT interval and might increase the risk of Torsade de Pointes, such as phenothiazine anti-psychotics, tricyclic antidepressants, certain oral macrolide antibiotics, and Class I and III antiarrhythmics
  • QTc Bazett interval ≥ 500 ms or PR interval > 280 ms
  • Severe hepatic impairment
  • Pregnant women
  • Nursing mothers

About this study

The primary objective of this study is to demonstrate how dronedarone (Multaq®) may aid in the slowing of progression of left atrial and ventricular fibrosis in patients with atrial fibrillation as assessed by late gadolinium enhanced magnetic resonance imaging.

Read the detailed description

BACKGROUND AND INTRODUCTION:

Atrial fibrillation (AF) arises as a result of a complex interaction between triggers, perpetuators and substrate. As early as 1995, Morillo et al have demonstrated that AF is associated with ultrastructural changes in myocytes. In animal models, alterations in myocytes after sustained AF resemble those of myocardial hybernation with a phenotypical adaptation towards a more fetal stage. Ultimately, these structural changes would lead to Calcium overload and metabolic stress, similar changes have been observed in humans. However, in humans, atrial dilatation and degenerative changes have been observed. Interstitial fibrosis (caused by deposits of collagen and fibronectin) is the prime cause of structural remodeling in left atrium (Boldt et al., 2004). It has been well established that fibrosis is a confounding clinical factor in causing AF (Kostin et al., 2002). But AF itself promotes fibrosis, which in turn leads to increased conduction heterogeneity within the atrial substrate resulting in further progression of AF (Everett,and Olgin, 2007).

The recent introduction of Late Gadolinium enhancement magnetic resonance imaging (LGE-MRI) sequence now allows for non-invasive assessment of the location and extent of arrhythmia related fibrosis.

Contrast enhancement occurs as a result of altered washout kinetics of gadolinium relative to normal surrounding tissue, which may reflect increased fibrosis or tissue remodeling of the myocardium. Our group has demonstrated the feasibility of a new LGE-MRI acquisition and processing protocol to detect fibrosis in the LA.

To date, no controlled trials evaluating the effect of antiarrhythmic drugs (AAD) and regression of left atrial fibrosis as assessed by LGE-MRI has been performed. We propose to use LGE-MRI to evaluate the effects of dronedarone vs. placebo on atrial and ventricular fibrosis. It has been shown that the success of catheter ablation procedure (which has been shown to be superior in terms of maintaining sinus rhythm in AF patients when compared to anti-arrhythmic drugs) is dependent upon the extent of fibrosis (Akoum et al., in prep). In AF patients with greater than 35% enhancement (percent left atrial fibrosis), the success of catheter ablation in reducing AF recurrence is greatly reduced. Hence for these patients, a drug that can control the progression of fibrosis and simultaneously provide respite from AF recurrence would be an extremely desirable prescription.

Multaq® is the chosen drug in this study because clinical trials (Hohnloser et al., 2009) have shown that it has the potential to reduce incidence of hospitalizations due to cardiovascular events by 25.5% and death in AF patients by 45%. We acknowledge the information that Dronedarone may be more prone to AF recurrence, however, it has a better safety profile with regards to thyroid and neurologic events and does not interfere with oral anticoagulants (Le Heuzey et al., 2010), which make dronedarone a more preferred antiarrhythmic drug to be used for this study. Furthermore, in patients who took dronedarone post cardioversion procedure to revert arrhythmia back to normal sinus rhythm (NSR), dronedarone has been shown to decrease AF recurrences (Le Heuzey et al., 2010).

OBJECTIVES:

Primary:

The primary objective of this study is to demonstrate how dronedarone may aid in the regression or slowing of progression of left atrial and ventricular fibrosis in patients with atrial fibrillation as assessed by LGE-MRI, using longitudinal data from a double-blinded, prospective study of patients diagnosed with atrial fibrillation over a twelve month follow up period.

Secondary:

  • To study the effects of dronedarone in global parameters of myocardial remodeling such as right and left atrial volumes and right and left ventricular volumes.
  • To study correlation between AF burden expressed as percentage of AF measured by an 8-day Holter Monitoring at three, six and twelve months post initiation.
Being tested
dronedarone, Placebo
Keywords
Multaq, dronedarone, Atrial Fibrillation
Medical subject headings
Atrial Fibrillation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • dronedaroneDrug

    Also called Multaq®

    Dronedarone will be prescribed by the patient's team according to established guidelines.

  • PlaceboDrug

    Placebo will be administered by the patient's team according to established guidelines.

Study groups in NCT01182376
Study groupRoleWhat they receive
PlaceboPlacebo comparatorHalf of the patients will be assigned placebo.
Receives: Drug: Placebo
Multaq® (dronedarone)ExperimentalHalf of the patients will be prescribed dronedarone.
Receives: Drug: dronedarone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. LA Fibrosis

    The change in left atrial fibrosis percentage, as measured on a scale, using MRI imaging, from baseline to the end of treatment.

    Measured: baseline, 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Aug 2010 (estimated)
  2. Study startNov 2010
  3. Primary completionDec 2012
  4. Study completionDec 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01182376
Sponsor's protocol ID
IRB_00040931
Acronym
SOAR
Status last verified
Jan 2016
First submitted
11 Aug 2010
Last updated
19 Feb 2016
Data monitoring committee
Yes

Publications

  • Swynghedauw B. Molecular mechanisms of myocardial remodeling. Physiol Rev. 1999 Jan;79(1):215-62. doi: 10.1152/physrev.1999.79.1.215.

    PubMed 9922372
  • Oral H, Pappone C, Chugh A, Good E, Bogun F, Pelosi F Jr, Bates ER, Lehmann MH, Vicedomini G, Augello G, Agricola E, Sala S, Santinelli V, Morady F. Circumferential pulmonary-vein ablation for chronic atrial fibrillation. N Engl J Med. 2006 Mar 2;354(9):934-41. doi: 10.1056/NEJMoa050955.

    PubMed 16510747
  • Lee SH, Tai CT, Hsieh MH, Tsai CF, Lin YK, Tsao HM, Yu WC, Huang JL, Ueng KC, Cheng JJ, Ding YA, Chen SA. Predictors of early and late recurrence of atrial fibrillation after catheter ablation of paroxysmal atrial fibrillation. J Interv Card Electrophysiol. 2004 Jun;10(3):221-6. doi: 10.1023/B:JICE.0000026915.02503.92.

    PubMed 15133358
  • Oral H, Knight BP, Ozaydin M, Tada H, Chugh A, Hassan S, Scharf C, Lai SW, Greenstein R, Pelosi F Jr, Strickberger SA, Morady F. Clinical significance of early recurrences of atrial fibrillation after pulmonary vein isolation. J Am Coll Cardiol. 2002 Jul 3;40(1):100-4. doi: 10.1016/s0735-1097(02)01939-3.

    PubMed 12103262
  • O'Donnell D, Furniss SS, Dunuwille A, Bourke JP. Delayed cure despite early recurrence after pulmonary vein isolation for atrial fibrillation. Am J Cardiol. 2003 Jan 1;91(1):83-5. doi: 10.1016/s0002-9149(02)03005-9. No abstract available.

    PubMed 12505579
  • Vasamreddy CR, Lickfett L, Jayam VK, Nasir K, Bradley DJ, Eldadah Z, Dickfeld T, Berger R, Calkins H. Predictors of recurrence following catheter ablation of atrial fibrillation using an irrigated-tip ablation catheter. J Cardiovasc Electrophysiol. 2004 Jun;15(6):692-7. doi: 10.1046/j.1540-8167.2004.03538.x.

    PubMed 15175066
  • Lo LW, Tai CT, Lin YJ, Chang SL, Wongcharoen W, Hsieh MH, Tuan TC, Udyavar AR, Hu YF, Chen YJ, Tsao HM, Chen SA. Mechanisms of recurrent atrial fibrillation: comparisons between segmental ostial versus circumferential pulmonary vein isolation. J Cardiovasc Electrophysiol. 2007 Aug;18(8):803-7. doi: 10.1111/j.1540-8167.2007.00848.x. Epub 2007 May 14.

    PubMed 17504254
  • Pappone C, Oreto G, Rosanio S, Vicedomini G, Tocchi M, Gugliotta F, Salvati A, Dicandia C, Calabro MP, Mazzone P, Ficarra E, Di Gioia C, Gulletta S, Nardi S, Santinelli V, Benussi S, Alfieri O. Atrial electroanatomic remodeling after circumferential radiofrequency pulmonary vein ablation: efficacy of an anatomic approach in a large cohort of patients with atrial fibrillation. Circulation. 2001 Nov 20;104(21):2539-44. doi: 10.1161/hc4601.098517.

    PubMed 11714647
  • Riley MJ, Marrouche NF. Ablation of atrial fibrillation. Curr Probl Cardiol. 2006 May;31(5):361-90. doi: 10.1016/j.cpcardiol.2006.01.002.

    PubMed 16690376
  • Wazni OM, Marrouche NF, Martin DO, Verma A, Bhargava M, Saliba W, Bash D, Schweikert R, Brachmann J, Gunther J, Gutleben K, Pisano E, Potenza D, Fanelli R, Raviele A, Themistoclakis S, Rossillo A, Bonso A, Natale A. Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial. JAMA. 2005 Jun 1;293(21):2634-40. doi: 10.1001/jama.293.21.2634.

    PubMed 15928285
  • Oakes RS, Badger TJ, Kholmovski EG, Akoum N, Burgon NS, Fish EN, Blauer JJ, Rao SN, DiBella EV, Segerson NM, Daccarett M, Windfelder J, McGann CJ, Parker D, MacLeod RS, Marrouche NF. Detection and quantification of left atrial structural remodeling with delayed-enhancement magnetic resonance imaging in patients with atrial fibrillation. Circulation. 2009 Apr 7;119(13):1758-67. doi: 10.1161/CIRCULATIONAHA.108.811877. Epub 2009 Mar 23.

    PubMed 19307477
  • Badger TJ, Oakes RS, Daccarett M, Burgon NS, Akoum N, Fish EN, Blauer JJ, Rao SN, Adjei-Poku Y, Kholmovski EG, Vijayakumar S, Di Bella EV, MacLeod RS, Marrouche NF. Temporal left atrial lesion formation after ablation of atrial fibrillation. Heart Rhythm. 2009 Feb;6(2):161-8. doi: 10.1016/j.hrthm.2008.10.042. Epub 2008 Nov 6.

    PubMed 19187904
  • Sinha AM, Schmidt M, Marschang H, Gutleben K, Ritscher G, Brachmann J, Marrouche NF. Role of left ventricular scar and Purkinje-like potentials during mapping and ablation of ventricular fibrillation in dilated cardiomyopathy. Pacing Clin Electrophysiol. 2009 Mar;32(3):286-90. doi: 10.1111/j.1540-8159.2008.02233.x.

    PubMed 19272055
  • Badger TJ, Adjei-Poku YA, Marrouche NF. MRI in cardiac electrophysiology: the emerging role of delayed-enhancement MRI in atrial fibrillation ablation. Future Cardiol. 2009 Jan;5(1):63-70. doi: 10.2217/14796678.5.1.63.

    PubMed 19371204
  • Weber KT, Weglicki WB, Simpson RU. Macro- and micronutrient dyshomeostasis in the adverse structural remodelling of myocardium. Cardiovasc Res. 2009 Feb 15;81(3):500-8. doi: 10.1093/cvr/cvn261. Epub 2008 Oct 3.

    PubMed 18835843

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing dronedarone in people with Atrial Fibrillation, run by University of Utah.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Feb 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

LA Fibrosis (time frame: baseline, 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01182376, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Feb 2016.

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SOAR Clinical Trial NCT01182376 | AzTrials