Cardiac Resynchronization in Atrial Fibrillation Trial - a Pilot Study

Heart Failure Clinical Trial

— Pilot-CRAfT  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01850277
• Other study ID #: IK-NP-0021-47/1378/13
• Status: Recruiting
• Phase: Phase 4
• First received: April 22, 2013
• Last updated: March 9, 2015
• Start date: October 2013
• Est. completion date: March 2017

Study information

• Verified date: March 2015
• Source: Institute of Cardiology, Warsaw, Poland
• Contact: Jan B Ciszewski, MD
• Phone: 223434050
• Email: jciszewski[@]ikard.pl
• Is FDA regulated: No
• Health authority: Poland: The Central Register of Clinical Trials
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: March 2017
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Atrial Fibrillation
• Heart Failure

Intervention

Drug:
• Amiodarone
The pharmacological treatment in the rhythm control strategy consist of amiodarone given orally including the loading dose up to 600mg daily - for the first 4 weeks. Then, a maintenance dose of 200mg/daily is prescribed. The use of other anti-arrhythmic agents is possible unless they are contraindicated. The introduction of amiodarone must not be performed unless the patient is treated effectively with oral anticoagulants for 3 weeks at least. Discontinuation of amiodarone results neither in withdrawal from the study nor in change of the treatment arm.

Procedure:
• External electrical cardioversion (EEC)
The first EEC is performed after the loading dose of amiodarone has been administered. A maximal number of shocks during one cardioversion is 3. The amount of the energy delivered during shocks is left at discretion of a physician performing the EEC. The EEC must be performed in accordance with the present guidelines on EEC and post-procedural care and the state of art. If atrial fibrillation reoccur, the patient should undergo a next EEC as soon as possible but preserving the safety time margins (i.e. effective anticoagulation period). The maximal no. of EEC procedures is 3. If sinus rhythm resumption or its maintenance is impossible or AF reoccur after the 3rd EEC, a strategy of rhythm control is discontinued and a rate control strategy is implemented.

Drug:
• Pharmacotherapy to slow and control ventricular rate
The pharmacotherapy should be consistent with current guidelines. It should include negative chronotropic and negative dromotropic agents such as beta-blockers, digitalis and amiodarone (the use of other, less popular agents, is also possible). The choice of the agents as well as their dosages are left at discretion of the treating physician. The goal of the therapy is to obtain BiVp% >95%

Procedure:
• Atrioventricular junction ablation (AVJA)
The procedure of atrioventricular junction ablation is dedicated to the patients in the rate control group in who the rate control is unsatisfactory. An AVJA procedure is not obligatory. The decision to perform an AVJA should be discussed with the patient and should be made collectively by the therapeutic team.

Locations

Country	Name	City	State
Poland	Institute of Cardiology, II Dept. of Coronary Heart Disease	Warsaw

Sponsors (1)

Lead Sponsor	Collaborator
Institute of Cardiology, Warsaw, Poland

Country where clinical trial is conducted

Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Identification of the factors predicting the response to the rhythm control strategy	Identification of the patients which benefit the most from the rhythm control strategy and comparison of their baseline characteristics with the whole group. Identification of non-responders to the rhythm control strategy and comparison of their baseline characteristics with the whole group. (multiple regression analysis).	1 year	No
Primary	BiVp%	Percentage of effective biventricular paced beats during 1st year (mean percentage from baseline to the control visit in 12th month) .	1 year	No
Secondary	6MWT distance	6 minute walk test distance (in meters)measured at 1 year from baseline	1 year	No
Secondary	peak VO2	Peak oxygen uptake (peak VO2) measured by means of cardiopulmonary exercise test at 1 year from baseline	1 year	No
Secondary	NYHA class	Heart failure (HF) symptoms escalation measured in New York Heart Association (NYHA) classes at 1 year from baseline	1 year	No
Secondary	Ejection fraction	Ejection fraction (EF) [%] assessed in ECHO at 1 year from baseline	1 year	No
Secondary	LVEDD reduction from baseline at 1 year	Change from baseline in left ventricle end-diastolic diameter (LVEDD) in ECHO at 1 year	baseline and 1 year	No
Secondary	LVEDV reduction from baseline at 1 year	Change from baseline in left ventricle end-diastolic volume (LVEDV) in ECHO at 1 year	baseline and 1 year	No
Secondary	LVESD reduction from baseline at 1 year	Change from baseline in left ventricle end-systolic diameter (LVESD) in ECHO at 1 year	baseline and 1 year	No
Secondary	LVESV reduction froma baseline at 1 year	Change from baseline in left ventricle end-systolic volume (LVESV) in ECHO at 1 year	baseline and 1 year	No
Secondary	Reduction of LA diameter at 1 year	Change from baseline in left atrium diameter assessed in ECHO at 1 year	baseline and 1 year	No
Secondary	Reduction of mitral regurgitation at 1 year	Change from baseline in mitral regurgitation measured in ECHO at 1 year	baseline and 1 year	No
Secondary	Heart failure exacerbations	Number of heart failure exacerbations in the treatment arm in 1 year time from baseline	up to 1 year	Yes
Secondary	Mortality	Numer of deaths assesed in 1 year follow-up	up to 1 year	Yes
Secondary	Stroke/TIA	Stroke or transient ischemic attack (TIA) during a year follow-up	up to 1 year	Yes
Secondary	CV mortality	Death due to cardiovascular (CV) causes during a year follow-up	up to 1 year	Yes
Secondary	Cardiovascular hospitalizations	Number of hospitalizations due to cardiovascular causes during a year follow-up	up to 1 year	Yes
Secondary	Quality of Life	The quality of life measured with the Minnesota Living with Heart Failure Questionaire (MLHFQ) at 1 year from baseline	1 year	No
Secondary	AF prevalence	Measurement of the prevalence of atrial fibrillation (precentage of participants with AF) at 1 year from baseline	1 year	No
Secondary	Ventricular arrhythmia	Number of ventricular arrhythmias (VF/"Torsade de Pointes" VT/sVT/nsVT) during the first year from basline	up to 1 year	Yes
Secondary	Electrotherapy	The number of high-energy interventions ("shocks") including separately: adequate shocks, inadequate shocks, electrical storm applies only to the patients with CRT-D device during the first year from baseline	up to 1 year	Yes
Secondary	Side effects	Overall number of side effects cases and complications cases of the treatment strategies related to: the device, the pharmacotherapy, the electrotherapy during the first year from baseline.	1 year	Yes
Secondary	6MWT distance	6 minute walk test distance (in meters) at 3 months from baseline	3 months	No
Secondary	peak VO2	Peak oxygen uptake (peak VO2) measured by means of cardiopulmonary exercise test at 3 months from baseline	3 months	No
Secondary	NYHA class	Heart failure (HF) symptoms escalation measured in New York Heart Association (NYHA) classes at 3 months from baseline	3 months	No
Secondary	Ejection fraction	Ejection fraction (EF) [%] assessed in ECHO at 3 months from baseline	3 months	No
Secondary	LVEDD reduction	Change from baseline in left ventricle end-diastolic diameter (LVEDD) reduction in ECHO at 3 months	baseline and 3 months	No
Secondary	LVEDV reduction	Change from baseline in left ventricle end-diastolic volume (LVEDV) reduction in ECHO at 3 months	baseline and 3 months	No
Secondary	Reduction of LA area	Change from baseline in left atrium area assessed in ECHO at 1 year	baseline and 1 year	No
Secondary	Reduction of LA diameter	Change from baseline in left atrium diameter assessed in ECHO at 3 months	baseline and 3 months	No
Secondary	Reduction of mitral regurgitation	Change from baseline in mitral regurgitation measured in ECHO at 3 months	baseline and 3 months	No
Secondary	Stroke/TIA	Stroke or transient ischemic attack (TIA) during the first 3 months from baseline	up to 3 months	Yes
Secondary	Quality of Life	The quality of life measured with the Minnesota Living with Heart Failure Questionaire (MLHFQ) at 3 months from baseline	3 months	No
Secondary	BiVp%	Percentage of effective biventricular paced beats during first 3 months from baseline.	3 months	No
Secondary	AF prevalence	Measurement of the prevalence of atrial fibrillation (precentage of participants with AF) at 3 month from baseline	3 months	No
Secondary	Electrotherapy	The number of high-energy interventions ("shocks") including separately: adequate shocks, inadequate shocks, electrical storm applies only to the patients with CRT-D device during first 3 months from baseline	up to 3 months	Yes
Secondary	Ventricular arrhythmia	Number of ventricular arrhythmias (VF/"Torsade de Pointes" VT/sVT/nsVT) during the first 3 months from basline	up to 3 months	Yes
Secondary	Side effects	Overall number of cases of side effects and complications of the treatment strategies related to: device, pharmacotherapy, electrotherapy during the first 3 months from baseline.	3 months	Yes
Secondary	Reduction of LA area	Change from baseline in left atrium area assessed in ECHO at 3 months	baseline and 3 month	No