Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12613000461796
Ethics application status
Approved
Date submitted
16/04/2013
Date registered
23/04/2013
Date last updated
24/04/2013
Type of registration
Prospectively registered

Titles & IDs
Public title
Impact of pacemaker on cardiac function
Scientific title
The effect of permanent pacemaker implantation with lead in right ventricular apex (RVA) versus right ventricular outflow tract (RVOT) on cardiac function in patients requiring pacemakers due to heart block
Secondary ID [1] 282353 0
Nil
Universal Trial Number (UTN)
Trial acronym
“SELECT SITE” STUDY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Block 288917 0
Pacemaker lead implantation 288918 0
Cardiac Function 288919 0
Condition category
Condition code
Cardiovascular 289263 289263 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Consecutive patients with AV block, scheduled to undergo dual chamber pacemaker implantation will be recruited into the study. Patients will be randomised to RVOT (Intervention arm) or RVA (Control arm) pacing groups according to a computer generated randomisation schedule.
Patients who are randomised to intervention arm will have the pacemaker lead implanted in the right ventricular outflow tract (RVOT). These patients will be followed up 6 monthly for the period of study i.e 36 months and will have investigations as per schedule .
The total duration of the procedure will be 60-90 minutes.
Intervention code [1] 286976 0
Treatment: Devices
Intervention code [2] 286977 0
Treatment: Surgery
Comparator / control treatment
Patients in the control arm will have pacemaker right ventricular lead implanted in Right ventricular apex (RVA). Rest of the procedure will be same in both arms. These patients will be followed up 6 monthly in the pacemaker clinic and will have investigations as per schedule for the period of study i.e 36 months.
The total duration of the procedure will be 60-90 minutes.
Control group
Active

Outcomes
Primary outcome [1] 289368 0
Investigate the effect of apical and septal right ventricular site pacing on left ventricular structural change and ejection fraction using cardiac MRI in RVA group.
Timepoint [1] 289368 0
At 12 months, 24 months and 36 months.
Secondary outcome [1] 302334 0
Quality of life( QOL) Assessed by
*New York Heart Association Functional class
*subjective validated patient scoring algorithm (SF36/ MLWHF)
* 6 min walk test.
Timepoint [1] 302334 0
12,24,36 MONTHS
Secondary outcome [2] 302335 0
Effect on cardiac Biomarkers assessed by :
N-terminal pro-hormone brain natriuretic peptide (NT pro-BNP), High sensitivity C reactive Protein (HsCRP)
Timepoint [2] 302335 0
12,24,36 MONTHS
Secondary outcome [3] 302336 0
New-onset atrial tachyarrhythmia assessed by pacemaker check
Timepoint [3] 302336 0
AT 12,24,36 MONTHS
Secondary outcome [4] 302337 0
The Effect of cardiac remodeling on its hemodynamics assessed by 6 min walk test,cardiopulmonary VO2 Max test and Echo parameters.
Timepoint [4] 302337 0
12,24,36 MONTHS
Secondary outcome [5] 302338 0
Lead-related complications such as lead dislodgement, myocardial perforation, lead integrity failure
Timepoint [5] 302338 0
12,24,36 MONTHS
Secondary outcome [6] 302339 0
The impact of ventricular pacing site to right ventricular and atrial remodelling by cardiac MRI and Echocardiogram
Timepoint [6] 302339 0
12,24,36 MONTHS
Secondary outcome [7] 302375 0
Biomarkers of myocardial fibrosis e.g. MMP-9, TIMP-1.
Timepoint [7] 302375 0
12,24,36 months
Secondary outcome [8] 302376 0
New onset heart failure, heart failure related hospitalizations. CRT-P, CRT-D or AICD upgrade from History
Timepoint [8] 302376 0
At 12,24,36 Months

Eligibility
Key inclusion criteria
Age >18 years old
Patients with high grade AV block
Able and willing to comply with all pre-, post- and follow-up testing, and requirements
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients indicated for an Implantable Cardioverter Defibrillator or Cardiac Resynchronization Therapy.
Myocardial Infarction, Bypass surgery or Valve replacement within 3 months prior to enrollment.
Patients where a right ventricular lead cannot be placed i.e. complex congenital heart disease.
Patients with hypertrophic obstructive cardiomyopathy.
Patients with acute coronary syndrome, unstable angina, severe mitral regurgitation and/or hemodynamically significant aortic stenosis.
Known permanent atrial fibrillation prior to enrollment.
Terminal conditions with a life expectancy of less than two years.
Participation in any other study that would confound the results of this study.
Psychological or emotional problems that may interfere.
Pregnant patients.
Musculo- skeletal disease hampering the realization of a 6-minute walk-test.
Previous non MRI compatible device
Renal Dysfunction with eGFR < 60ml/min
Any contraindication for MRI

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Consecutive patients with AV block, scheduled to undergo dual chamber pacemaker implantation will be recruited into the study.Enrolment into the study will be made by independent research nurse if the patient meets the inclusion and exclusion criteria. This nurse will not be involved in randomisation of the patient and will be done by investigators. Patients will be randomised to RVOTS or RVA pacing groups according to a computer generated randomisation schedule. The total number of patients screened to obtain the sample, and reasons for their exclusion, will be recorded.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated randomisation will be used
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The statistical methodology for the study has been determined in consultation with the Data Management and Analysis Centre, University of Adelaide. The primary endpoint of the study is time to development of LV systolic dysfunction in RVA group.
All analyses will be based on the intention to treat principle. The primary outcome of time to development of LV systolic dysfunction in RVA group will be compared between randomised groups using a Cox proportional hazards model. Differences between the groups will be expressed using a hazard ratio and 95% confidence interval. Key secondary outcomes such as rates of atrial or ventricular arrhythmia episodes will be analysed using either Cox proportional hazards models or Fine and Gray competing risks regression as appropriate. Continuous secondary outcomes such as the 6-minute walking distance, SF36 scores, MLWHF score will be compared between randomised groups over time using linear mixed effects models.
All continuous variables will be reported as mean +/- standard deviation where normally distributed. Mixed effects modelling will be employed to evaluate the difference in LV ejection fraction as a primary endpoint between the two groups. Statistical significance will be two-sided and will be established at p<0.05.
Echocardiographic, haemodynamic, and CMR outcomes for patients will be evaluated as described above. Symptomatic outcomes will be evaluated by NYHA classification and by SF36 and MLWHF score. Objective change in functional capacity will be measured by 6-minute walk distance and by VO2 PEAK .
The outcomes of the study groups will be compared by mixed effects modelling to determine the effect of pacing modality on the primary endpoint.

Power Calculation : The patient numbers have been selected based on previous published literature evaluating the change in LV ejection fraction using RVA pacing versus RVOTS pacing. Ninety patients are required in each group to find a 5% difference in follow-up LV ejection fraction with a power of 90% and a significance level set at 0.05 assuming a common baseline LVEF of 60% with standard deviation of 10%.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/05/2013
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
180
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,QLD,SA,WA,VIC
Recruitment hospital [1] 899 0
The Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 6764 0
5000 - Adelaide
Recruitment postcode(s) [2] 6765 0
5001 - Adelaide
Recruitment postcode(s) [3] 6766 0
5086 - Manningham

Funding & Sponsors
Funding source category [1] 287121 0
University
Name [1] 287121 0
University of Adelaide
Country [1] 287121 0
Australia
Primary sponsor type
University
Name
University of Adelaide, Centre for Heart Rhythm Disorder
Address
Royal Adelaide Hospital
North Terrace
Adelaide
South Australia
5000
Country
Australia
Secondary sponsor category [1] 285891 0
Commercial sector/Industry
Name [1] 285891 0
Medtronic
Cardiac Rhythm Disease Management External Research Program
Address [1] 285891 0
Clinical Research Manager, CRDM
Medtronic Australasia Pty Ltd.
97 Waterloo Road ; North Ryde, NSW 2113 Australia
Country [1] 285891 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289124 0
Royal Adelaide Human Ethics Committee
Ethics committee address [1] 289124 0
Ethics committee country [1] 289124 0
Australia
Date submitted for ethics approval [1] 289124 0
Approval date [1] 289124 0
22/01/2013
Ethics approval number [1] 289124 0
HREC/12/RAH/174

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 39358 0
Prof Prashanthan Sanders
Address 39358 0
Centre For Heart Rhythm Disorder
Royal Adelaide Hospital
North Terrace
Adelaide
SA
5000
Country 39358 0
Australia
Phone 39358 0
+61 8 8222 2723
Fax 39358 0
Email 39358 0
[email protected]
Contact person for public queries
Name 39359 0
Prashanthan Sanders
Address 39359 0
Centre For Heart Rhythm Disorder
Royal Adelaide Hospital
North Terrace
Adelaide
SA
5000
Country 39359 0
Australia
Phone 39359 0
+61 8 8222 2723
Fax 39359 0
Email 39359 0
[email protected]
Contact person for scientific queries
Name 39360 0
Prashanthan Sanders
Address 39360 0
Centre For Heart Rhythm Disorder
Royal Adelaide Hospital
North Terrace
Adelaide
SA
5000
Country 39360 0
Australia
Phone 39360 0
+61 8 8222 2723
Fax 39360 0
Email 39360 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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