Cardiac Resynchronization in Atrial Fibrillation Trial - a Pilot Study (Pilot-CRAfT)

This study is not yet open for participant recruitment.
Verified May 2013 by Institute of Cardiology, Warsaw, Poland
Sponsor:
Information provided by (Responsible Party):
Institute of Cardiology, Warsaw, Poland
ClinicalTrials.gov Identifier:
NCT01850277
First received: April 22, 2013
Last updated: May 6, 2013
Last verified: May 2013
  Purpose

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.


Condition Intervention Phase
Atrial Fibrillation
Heart Failure
Drug: Amiodarone
Procedure: External electrical cardioversion (EEC)
Drug: Pharmacotherapy to slow and control ventricular rate
Procedure: Atrioventricular junction ablation (AVJA)
Phase 4

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

Resource links provided by NLM:


Further study details as provided by Institute of Cardiology, Warsaw, Poland:

Primary Outcome Measures:
  • BiVp% [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Percentage of effective biventricular paced beats during 1st year (mean percentage from baseline to the control visit in 12th month) .


Secondary Outcome Measures:
  • 6MWT distance [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    6 minute walk test distance (in meters)measured at 1 year from baseline

  • peak VO2 [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Peak oxygen uptake (peak VO2) measured by means of cardiopulmonary exercise test at 1 year from baseline

  • NYHA class [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Heart failure (HF) symptoms escalation measured in New York Heart Association (NYHA) classes at 1 year from baseline

  • Ejection fraction [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Ejection fraction (EF) [%] assessed in ECHO at 1 year from baseline

  • LVEDD reduction from baseline at 1 year [ Time Frame: baseline and 1 year ] [ Designated as safety issue: No ]
    Change from baseline in left ventricle end-diastolic diameter (LVEDD) in ECHO at 1 year

  • LVEDV reduction from baseline at 1 year [ Time Frame: baseline and 1 year ] [ Designated as safety issue: No ]
    Change from baseline in left ventricle end-diastolic volume (LVEDV) in ECHO at 1 year

  • LVESD reduction from baseline at 1 year [ Time Frame: baseline and 1 year ] [ Designated as safety issue: No ]
    Change from baseline in left ventricle end-systolic diameter (LVESD) in ECHO at 1 year

  • LVESV reduction froma baseline at 1 year [ Time Frame: baseline and 1 year ] [ Designated as safety issue: No ]
    Change from baseline in left ventricle end-systolic volume (LVESV) in ECHO at 1 year

  • Reduction of LA diameter at 1 year [ Time Frame: baseline and 1 year ] [ Designated as safety issue: No ]
    Change from baseline in left atrium diameter assessed in ECHO at 1 year

  • Reduction of mitral regurgitation at 1 year [ Time Frame: baseline and 1 year ] [ Designated as safety issue: No ]
    Change from baseline in mitral regurgitation measured in ECHO at 1 year

  • Heart failure exacerbations [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]
    Number of heart failure exacerbations in the treatment arm in 1 year time from baseline

  • Mortality [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]
    Numer of deaths assesed in 1 year follow-up

  • Stroke/TIA [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]
    Stroke or transient ischemic attack (TIA) during a year follow-up

  • CV mortality [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]
    Death due to cardiovascular (CV) causes during a year follow-up

  • Cardiovascular hospitalizations [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]
    Number of hospitalizations due to cardiovascular causes during a year follow-up

  • Quality of Life [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    The quality of life measured with the Minnesota Living with Heart Failure Questionaire (MLHFQ) at 1 year from baseline

  • AF prevalence [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Measurement of the prevalence of atrial fibrillation (precentage of participants with AF) at 1 year from baseline

  • Ventricular arrhythmia [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]
    Number of ventricular arrhythmias (VF/"Torsade de Pointes" VT/sVT/nsVT) during the first year from basline

  • Electrotherapy [ Time Frame: up to 1 year ] [ Designated as safety issue: Yes ]
    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

  • Side effects [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    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.

  • 6MWT distance [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    6 minute walk test distance (in meters) at 3 months from baseline

  • peak VO2 [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Peak oxygen uptake (peak VO2) measured by means of cardiopulmonary exercise test at 3 months from baseline

  • NYHA class [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Heart failure (HF) symptoms escalation measured in New York Heart Association (NYHA) classes at 3 months from baseline

  • Ejection fraction [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Ejection fraction (EF) [%] assessed in ECHO at 3 months from baseline

  • LVEDD reduction [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
    Change from baseline in left ventricle end-diastolic diameter (LVEDD) reduction in ECHO at 3 months

  • LVEDV reduction [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
    Change from baseline in left ventricle end-diastolic volume (LVEDV) reduction in ECHO at 3 months

  • Reduction of LA area [ Time Frame: baseline and 1 year ] [ Designated as safety issue: No ]
    Change from baseline in left atrium area assessed in ECHO at 1 year

  • Reduction of LA diameter [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
    Change from baseline in left atrium diameter assessed in ECHO at 3 months

  • Reduction of mitral regurgitation [ Time Frame: baseline and 3 months ] [ Designated as safety issue: No ]
    Change from baseline in mitral regurgitation measured in ECHO at 3 months

  • Stroke/TIA [ Time Frame: up to 3 months ] [ Designated as safety issue: Yes ]
    Stroke or transient ischemic attack (TIA) during the first 3 months from baseline

  • Quality of Life [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    The quality of life measured with the Minnesota Living with Heart Failure Questionaire (MLHFQ) at 3 months from baseline

  • BiVp% [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Percentage of effective biventricular paced beats during first 3 months from baseline.

  • AF prevalence [ Time Frame: 3 months ] [ Designated as safety issue: No ]
    Measurement of the prevalence of atrial fibrillation (precentage of participants with AF) at 3 month from baseline

  • Electrotherapy [ Time Frame: up to 3 months ] [ Designated as safety issue: Yes ]
    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

  • Ventricular arrhythmia [ Time Frame: up to 3 months ] [ Designated as safety issue: Yes ]
    Number of ventricular arrhythmias (VF/"Torsade de Pointes" VT/sVT/nsVT) during the first 3 months from basline

  • Side effects [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    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.

  • Reduction of LA area [ Time Frame: baseline and 3 month ] [ Designated as safety issue: No ]
    Change from baseline in left atrium area assessed in ECHO at 3 months


Other Outcome Measures:
  • Identification of the factors predicting the response to the rhythm control strategy [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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).


Estimated Enrollment: 60
Study Start Date: May 2013
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rhythm control

In this group a strategy to restore and maintain SR, including amiodarone and an external electrical cardioversion (EEC), is implemented. A procedure of AF ablation is possible but not obligatory.

At baseline, patients assigned to the group undergo a standard 12-lead ECG, a 6-minute walk test (6MWT), a cardiopulmonary exercise test(CPX), an echocardiography(ECHO), a standard device control; a serum thyroid -stimulating hormone (TSH) level is assessed and patients fill the Minnesota Living With Heart Failure Questionnaire (MLHFQ). Control visits are performed every 3 months including a 12-lead ECG measurement and a device control. On the visits in the 3rd and 12th month an ECHO, a CPX, a 6MWT are performed and a MLHFQ is filled; control TSH levels are assessed every 6 months.

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.
Other Names:
  • Cordarone
  • Amiodaron
  • Pacerone
  • Aratac
  • Cardinorm
  • Rithmik
  • Arycor
  • Atlansil
  • Tachyra
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.

Active Comparator: Rate control

In the latter group a pharmacotherapy to slow and control ventricular rate by means of pharmacotherapy and an atrio-ventricular junction ablation (AVJA) is implemented.

At baseline, each patient assigned to the rate control group undergoes a standard 12-lead ECG, a 6MWT, a CPX, an ECHO, a standard device control and a serum TSH level assessed. Moreover, the patient fills the Minnesota Living With Heart Failure Questionaire (MLHFQ). The control visits are performed for one year, every 3 months including a standard 12-lead ECG measurement and standard control of the device. On the visits in the 3rd and 12th month additionally an ECHO, a CPX, a 6MWT are performed and a MLHFQ is filled. The control TSH levels are assessed every 6 months.

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%
Other Names:
  • beta-blockers
  • digitalis
  • amiodarone
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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01850277

Contacts
Contact: Jan B Ciszewski, MD 223434050 ext +48 jciszewski@ikard.pl

Locations
Poland
Institute of Cardiology, II Dept. of Coronary Heart Disease Not yet recruiting
Warsaw, Poland, 02-637
Contact: Jan B Ciszewski, MD    223434050 ext +48    jciszewski@ikard.pl   
Principal Investigator: Jan B Ciszewski, MD         
Sponsors and Collaborators
Institute of Cardiology, Warsaw, Poland
Investigators
Principal Investigator: Jan B Ciszewski, MD Institute of Cardiology, Warsaw, Poland
Study Chair: Maciej Sterlinski, MD, PhD Institute of Cardiology, Warsaw, Poland
  More Information

No publications provided

Responsible Party: Institute of Cardiology, Warsaw, Poland
ClinicalTrials.gov Identifier: NCT01850277     History of Changes
Other Study ID Numbers: IK-NP-0021-47/1378/13
Study First Received: April 22, 2013
Last Updated: May 6, 2013
Health Authority: Poland: The Central Register of Clinical Trials

Keywords provided by Institute of Cardiology, Warsaw, Poland:
Atrial fibrillation
Cardiac resynchronization therapy
Heart failure
Rhythm control strategy

Additional relevant MeSH terms:
Atrial Fibrillation
Heart Failure
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Adrenergic beta-Antagonists
Amiodarone
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Enzyme Inhibitors
Vasodilator Agents

ClinicalTrials.gov processed this record on April 22, 2014