Clinical trial NCT01850277: Cardiac Resynchronization in Atrial Fibrillation Trial - a Pilot Study
Official title: Comparison of a Rhythm Control Treatment Strategy Versus a Rate Control Strategy in Patients With Permanent or Long-term Persistent Atrial Fibrillation and Heart Failure Treated With Cardiac Resynchronization Therapy - a Pilot Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Atrial Fibrillation
Heart Failure
Keywords: Atrial fibrillation
Cardiac resynchronization therapy
Heart failure
Rhythm control strategy
Lead sponsor: National Institute of Cardiology, Warsaw, Poland
Sponsor class: OTHER
First posted: 2013-05-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this prospective randomized study is to determine whether patients on cardiac resynchronization therapy with concomitant long-standing persistent or permanent atrial fibrillation would benefit from a strategy to restore and maintain sinus rhythm (rhythm control strategy) in comparison to a rate control strategy in terms of higher biventricular paced beats percentage.

Detailed description: Due to a lack of sufficient data the present guidelines on treatment of patients with atrial fibrillation (AF) and cardiac resynchronization therapy (CRT) devices are of low scientific evidence. The efficacy of CRT in AF patients is limited by the percentage of the effective biventricular paced beats (BiVp%), which should exceed 95%-98% - a goal which is seldom obtained by means of pharmacological rate control strategy. The only treatment strategy which effect is scientifically established is an atrioventricular junction ablation (AVJA) but the use of this method is limited.

On the other hand, about 10% of patients with persistent forms of AF experience a spontaneous sinus rhythm (SR) resumption after CRT implantation. Moreover, SR resumption and it's maintenance by means of single external electrical cardioversion in AF patients has been proven feasible. A strategy of rhythm control in AF patients on CRT could provide high BiVp% and improve the efficacy of CRT in this group of patients.

To show superiority of the rhythm control strategy over the rate control strategy a sample size of 60 patients was calculated based on following assumptions: two-tailed test, a type I error of 0.05, a power of 80%, efficacy (mean BiVp%) of rate control strategy 90%, efficacy (mean BiVp%)of rhythm control strategy 98% and 8% drop-out rate to fulfill the criteria of intention-to-treat analysis. Due to presumed lack of statistical power the secondary end points and safety endpoints will be considered exploratory.

Eligibility criteria: Inclusion Criteria:

* Permanent or long-standing persistent atrial fibrillation (definitions according to the latest European Society of Cardiology guidelines on AF)
* At least 3 months after a procedure of a CRT device implantation
* A CRT device with a presence of a right atrial electrode
* Age: ≥18 years old
* Effectively biventricular paced captured beats \<95%
* Effective therapy with oral anticoagulants for at least 3 months
* Written informed consent

Exclusion Criteria:

* Reversible causes of AF
* Significant valve disease
* Advanced A-V block (including: AVJA)
* Contraindications to amiodarone (hyperthyroidism, not compensated hypothyroidism, drug intolerance, QT\>460ms for men, QT\>450 for women)
* Long-QT syndrome
* Decompensation of the heart failure within 48 hours before the qualification
* Cardiac transplantation in 6 months
* Life expectancy less than 1 year
* Chronic dialysis
* LA diameter \>6cm
* Alcohol abuse
* Pregnancy/lack of effective contraceptive therapy (in case of females in the reproductive age)
* Participation in other clinical trial

Primary outcomes:
measure: BiVp%
timeFrame: 1 year
Secondary outcomes:
measure: 6MWT distance
timeFrame: 1 year
measure: peak VO2
timeFrame: 1 year
measure: NYHA class
timeFrame: 1 year
measure: Ejection fraction
timeFrame: 1 year
measure: LVEDD reduction from baseline at 1 year
timeFrame: baseline and 1 year
measure: LVEDV reduction from baseline at 1 year
timeFrame: baseline and 1 year
measure: LVESD reduction from baseline at 1 year
timeFrame: baseline and 1 year
measure: LVESV reduction froma baseline at 1 year
timeFrame: baseline and 1 year
measure: Reduction of LA diameter at 1 year
timeFrame: baseline and 1 year
measure: Reduction of mitral regurgitation at 1 year
timeFrame: baseline and 1 year
measure: Heart failure exacerbations
timeFrame: up to 1 year
measure: Mortality
timeFrame: up to 1 year
measure: Stroke/TIA
timeFrame: up to 1 year
measure: CV mortality
timeFrame: up to 1 year
measure: Cardiovascular hospitalizations
timeFrame: up to 1 year
measure: Quality of Life
timeFrame: 1 year
measure: AF prevalence
timeFrame: 1 year
measure: Ventricular arrhythmia
timeFrame: up to 1 year
measure: Electrotherapy
timeFrame: up to 1 year
measure: Side effects
timeFrame: 1 year
measure: 6MWT distance
timeFrame: 3 months
measure: peak VO2
timeFrame: 3 months
measure: NYHA class
timeFrame: 3 months
measure: Ejection fraction
timeFrame: 3 months
measure: LVEDD reduction
timeFrame: baseline and 3 months
measure: LVEDV reduction
timeFrame: baseline and 3 months
measure: Reduction of LA area
timeFrame: baseline and 1 year
measure: Reduction of LA diameter
timeFrame: baseline and 3 months
measure: Reduction of mitral regurgitation
timeFrame: baseline and 3 months
measure: Stroke/TIA
timeFrame: up to 3 months
measure: Quality of Life
timeFrame: 3 months
measure: BiVp%
timeFrame: 3 months
measure: AF prevalence
timeFrame: 3 months
measure: Electrotherapy
timeFrame: up to 3 months
measure: Ventricular arrhythmia
timeFrame: up to 3 months
measure: Side effects
timeFrame: 3 months
measure: Reduction of LA area
timeFrame: baseline and 3 month
Other outcomes:
measure: Identification of the factors predicting the response to the rhythm control strategy
timeFrame: 1 year
Locations:
city: Warsaw
country: Poland
facility: Institute of Cardiology, II Dept. of Coronary Heart Disease
Study officials:
affiliation: National Institute of Cardiology, Warsaw, Poland
name: Jan B Ciszewski, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Institute of Cardiology, Warsaw, Poland
name: Maciej Sterlinski, MD, PhD
role: STUDY_CHAIR
References:
citation: Ciszewski J, Maciag A, Kowalik I, Syska P, Lewandowski M, Farkowski MM, Borowiec A, Chwyczko T, Pytkowski M, Szwed H, Sterlinski M. Comparison of the rhythm control treatment strategy versus the rate control strategy in patients with permanent or long-standing persistent atrial fibrillation and heart failure treated with cardiac resynchronization therapy - a pilot study of Cardiac Resynchronization in Atrial Fibrillation Trial (Pilot-CRAfT): study protocol for a randomized controlled trial. Trials. 2014 Oct 4;15:386. doi: 10.1186/1745-6215-15-386.