Cardiac Resynchronisation Therapy and AV Nodal Ablation Trial in Atrial Fibrillation Patients (CAAN-AF)

This study is currently recruiting participants.
Verified February 2014 by University of Adelaide
Sponsor:
Collaborators:
Medtronic
St. Jude Medical
Boston Scientific Corporation
Information provided by (Responsible Party):
Prashanthan Sanders, University of Adelaide
ClinicalTrials.gov Identifier:
NCT01522898
First received: January 25, 2012
Last updated: February 20, 2014
Last verified: February 2014
  Purpose

Cardiac resynchronization therapy (CRT) is a treatment for heart failure in patients who also suffer from ventricular dyssynchrony, a form of uncoordinated contraction of the ventricle (lower pumping chamber of the heart). In the past decade, CRT has become an established treatment for heart failure patients who are in normal rhythm, called sinus rhythm. An important subset of heart failure patients are those with atrial fibrillation (AF), who make up around 1 in 4 HF patients, and are over-represented amongst HF patients with more advanced symptoms. In heart failure patients with AF, CRT has proven not to be as effective as in sinus rhythm, due to competition between beats generated by the CRT device and beats conducted from the heart's own electrical conduction system. In the current study, we aim to test the hypothesis that ablating the AV node, which controls electrical conduction from the heart's atria (top chamber) to its ventricles (lower chambers), will improve survival and heart failure symptoms in CRT patients with co-existent AF. The results are important, because they will provide a way of passing on the benefits of CRT, such as improved survival, less heart failure symptoms, and better quality of life, to heart failure patients who also suffer from AF.


Condition Intervention
Heart Failure
Atrial Fibrillation
Procedure: AV nodal ablation
Drug: Medical Ventricular Rate Control

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Cardiac Resynchronisation Therapy and AV Nodal Ablation Trial in Atrial Fibrillation

Resource links provided by NLM:


Further study details as provided by University of Adelaide:

Primary Outcome Measures:
  • All-cause mortality and non-fatal heart failure events [ Time Frame: Final-analysis at completion of recruitment and follow-up period (minimum 2 year follow-up) ] [ Designated as safety issue: Yes ]

    This is a composite of all-cause mortality and non-fatal heart failure events. All-cause mortality will be determined by a designated clinical events committee.

    Heart Failure events will be documented by clinical data from the hospital In CAAN-AF, a subject will be described as having a "Heart Failure Event" when the subject has symptoms and/or signs consistent with congestive heart failure and:

    • responsive to parenteral diuretic or inotropic support as an outpatient
    • responsive to oral or parenteral diuretic or inotropic support during an inpatient stay


Secondary Outcome Measures:
  • All-cause mortality [ Time Frame: Final-analysis at completion of recruitment and follow-up period (minimum 2 year follow-up)f recruitment ] [ Designated as safety issue: Yes ]
    All-cause mortality will be determined after adjudication committee review of clinical records, and death certificate data.

  • Cardiovascular mortality [ Time Frame: Final-analysis at completion of recruitment and follow-up period (minimum 2 year follow-up) ] [ Designated as safety issue: Yes ]
    Cardiovascular deaths will be classified in terms of suddenness and arrhythmic mechanism according to the Hinkle-Thaler criteria.

  • Non-Fatal Heart Failure Events [ Time Frame: Final-analysis at completion of recruitment and follow-up period (minimum 2 year follow-up) ] [ Designated as safety issue: No ]

    Heart Failure events will be documented by clinical data from the hospital In CAAN-AF, a subject will be described as having a "Heart Failure Event" when the subject has symptoms and/or signs consistent with congestive heart failure and:

    • responsive to parenteral diuretic or inotropic support as an outpatient
    • responsive to oral or parenteral diuretic or inotropic support during an inpatient stay

  • 6-minute walking distance [ Time Frame: Final-analysis at completion of recruitment and follow-up period (minimum 2 year follow-up) ] [ Designated as safety issue: No ]
    6-minute walking distance will be measured according to standard criteria.

  • Quality of Life [ Time Frame: Final-analysis at completion of recruitment and follow-up period (minimum 2 year follow-up) ] [ Designated as safety issue: No ]
    Quality of life as assessed by the Short Form 36 (SF-36) questionnaire and Minnesota Living with Heart Failure Questionnaire

  • Unplanned Hospitalization [ Time Frame: Final-analysis at completion of recruitment and follow-up period (minimum 2 year follow-up) ] [ Designated as safety issue: Yes ]
    Unplanned hospital admissions will be assessed by a combination of patient self-report, hospital record and/or treating physician interrogation. The reason, date and duration of hospitalization will be recorded Planned hospitalizations (hospital visits for elective or planned medical interventions) will excluded from this outcome

  • Ventricular arrhythmias requiring device therapy [ Time Frame: Final-analysis at completion of recruitment and follow-up period (minimum 2 year follow-up) ] [ Designated as safety issue: No ]
    Ventricular arrhythmias requiring device therapy will be determined by implantable Cardioverter Defibrillator (ICD) interrogation records and clinical records. At each site, the number, duration and type (VT/VF) of device recorded arrhythmias will be recorded, as well as the need for device therapy (anti-tachycardia pacing and/or ICD shocks).


Other Outcome Measures:
  • Inappropriate shocks [ Time Frame: Final-analysis at completion of recruitment and follow-up period (minimum 2 year follow-up) ] [ Designated as safety issue: Yes ]
    The clinical events committee will review clinical records to ascertain if device therapies are appropriate or inappropriate.

  • Cardiovascular MRI prediction of response [ Time Frame: Final-analysis at completion of recruitment and follow-up period (minimum 2 year follow-up) ] [ Designated as safety issue: No ]
    Cardiovascular MRI will be performed in subjects eligible for this procedure prior to implantation of CRT device, when available. Cardiovascular MRI data will be evaluated for the ability to predict clinical CRT response.

  • Depression [ Time Frame: Final-analysis at completion of recruitment and follow-up period (minimum 2 year follow-up) ] [ Designated as safety issue: No ]
    Depression will be evaluated in all patients at specified clinical follow-up visits with the Center for Epidemiologic Studies Depression Scale (CES-D questionnaire).

  • Ventricular reverse remodelling [ Time Frame: Final-analysis at completion of recruitment and follow-up period (minimum 2 year follow-up) ] [ Designated as safety issue: No ]
    Left ventricular reverse remodeling will be assessed by echocardiographic parameters including left ventricular end systolic volume, left ventricular ejection fraction. An echocardiography core laboratory has been established to process images from individual trial sites for this purpose.


Estimated Enrollment: 590
Study Start Date: March 2013
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Medical Rate Control
Medical Rate Control aimed at ventricular rate target of 90 beats per minute. Specific medical therapy to be determined for each patient by individual clinician.
Drug: Medical Ventricular Rate Control
Ventricular Rate Control with target ventricular rate of 90 beats per minute.
Experimental: AV nodal ablation
AV node ablation performed by percutaneous catheter ablation, with endpoint of complete heart block.
Procedure: AV nodal ablation
Percutaneous catheter ablation of the AV node.
Other Name: His Bundle Ablation, AV junctional ablation

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years old
  • Persistent (≥ 1 month) or permanent atrial fibrillation. Persistent AF will be where obtaining and maintaining sinus rhythm is deemed either not worthwhile, or to be ineffective in the long term, or where both the patient and physician accept the presence of AF, where rhythm control intervention is, by definition no longer pursued. Permanent AF is defined as atrial fibrillation where sinus rhythm cannot be restored.
  • NYHA class II , III or ambulatory class IV heart failure
  • Left Ventricular Ejection Fraction (LVEF) ≤ 35% by objective criteria such as echocardiography, or cardiac MRI
  • QRS duration on 12-lead ECG ≥ 120ms
  • Able and willing to comply with all pre-, post- and follow-up testing and requirements.

Exclusion Criteria:

  • age < 18 years
  • pregnancy
  • previous AV nodal ablation
  • Second or third degree AV block
  • Inability to provide informed consent
  • life expectancy less than 24 months due to co-morbid illness other than heart failure erg cancer, end-stage renal disease, liver failure
  • Paroxysmal Atrial Fibrillation that self terminates within 7 days
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01522898

Contacts
Contact: Prashanthan Sanders, MBBS PhD +61-8-8222-2723 prash.sanders@adelaide.edu.au
Contact: Anand N Ganesan, MBBS PhD +61-8-8222-2723 anand.ganesan@adelaide.edu.au

Locations
Australia, New South Wales
John Hunter Hospital Recruiting
New Lambton, New South Wales, Australia, 2305
Contact: Anne Gordon, MD    (02) 4921 4720      
Principal Investigator: Malcolm Barlow, MD         
Sub-Investigator: Bradley Wilsmore, MBBS         
Sub-Investigator: James Leitch, MBBS         
Royal Prince Alfred Hospital Recruiting
Sydney, New South Wales, Australia
Principal Investigator: Raymond Sy, MBBS PhD         
Australia, Queensland
Prince Charles Hospital Recruiting
Chermside, Queensland, Australia, 4032
Contact: Bernice Enever    (07) 3139 5906      
Principal Investigator: Haris Haqqani, MBBS PhD         
Australia, South Australia
Royal Adelaide Hospital Recruiting
Adelaide, South Australia, Australia, 5000
Contact: Vanessa Maxwell    +61-8-8222-2723    vanessa.maxwell@adelaide.edu.au   
Principal Investigator: Prashanthan Sanders, MBBS PhD         
Sub-Investigator: Anand N Ganesan, MBBS PhD         
Sub-Investigator: Glenn D Young, MBBS         
Sub-Investigator: Kurt C Roberts-Thomson, MBBS PhD         
Sub-Investigator: Dennis H Lau, MBBS PhD         
Sub-Investigator: Richard Hillock, MBBS         
Flinders Medical Centre Recruiting
Bedford Park, South Australia, Australia, 5042
Contact: Deirdre Murphy    08-8820 4440      
Principal Investigator: Andrew McGavigan, MBChB, MD         
Sub-Investigator: William Heddle, MBBS         
Sub-Investigator: Cameron Singleton, MBBS PhD         
Australia, Victoria
The Alfred Hospital Recruiting
Melbourne, Victoria, Australia
Contact: Peter Kistler, MBBS PhD         
Royal Melbourne Hospital Recruiting
Parkville, Victoria, Australia, 3050
Contact: Karen L Halloran    +61393495400    Karen.Halloran@mh.org.au   
Principal Investigator: Jonathan M Kalman, MBBS PhD         
Australia, Western Australia
Royal Perth Hospital Recruiting
Perth, Western Australia, Australia
Contact: Mary Vorster    (08) 9224 8069      
Contact: Michelle Bonner         
Principal Investigator: Vince Paul, MBBS PhD         
Sub-Investigator: Timothy Gattorna, MBBS         
New Zealand
Waikato Hospital Recruiting
Hamilton, New Zealand, 3240
Contact: Liz Low    7839 7136      
Principal Investigator: Martin Stiles, MBChB PhD         
Sponsors and Collaborators
University of Adelaide
Medtronic
St. Jude Medical
Boston Scientific Corporation
Investigators
Principal Investigator: Prashanthan Sanders, MBBS PhD University of Adelaide
  More Information

No publications provided

Responsible Party: Prashanthan Sanders, Director, Centre for Heart Rhythm Disorders, University of Adelaide and Royal Adelaide Hospital, University of Adelaide
ClinicalTrials.gov Identifier: NCT01522898     History of Changes
Other Study ID Numbers: RAH-HREC-Protocol-#111234
Study First Received: January 25, 2012
Last Updated: February 20, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Australia: Human Research Ethics Committee
Australia: National Health and Medical Research Council

Keywords provided by University of Adelaide:
Heart Failure
Atrial Fibrillation

Additional relevant MeSH terms:
Atrial Fibrillation
Heart Failure
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on April 16, 2014