Comparison of Devices for Atrial Septal Defects Closure: A Pilot Study

Study Overview
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Brief Summary
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This is a proposal, for the first time in Canada, to examine the comparative effectiveness of three commercially available devices (ASO, FSO, and GAO/GSO) for transcatheter closure of atrial septal defects (ASD) in adults using a pilot randomized controlled trial.

Detailed Description
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The most widely used transcatheter device for ASD closure is the the Amplatzer Septal Occluder (ASO). Two other devices that entered the Canadian market are the Gore Cardioform ASD occluder (GAO) and the Figulla Flexible II Occlutech (FSO) device. There exists a paucity of data on the comparative efficacy and safety of these devices. This is a proposal, for the first time in Canada, to examine the comparative effectiveness of three commercially available ASD devices in an internal pilot randomized trial. Approximately 60 patients referred for transcatheter ASD closure will be recruited in this study over a period of 15 months from 4 participating centers across Canada. This will be a registry-based randomized controlled trial (RRCT) where patients will be enrolled into one of three arms (ASO, FSO, and GAO/GSO) to compare the effectiveness and safety outcomes of three different ASD closure devices.

Official Title
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Comparative Effectiveness of Three Devices for Transcatheter Closure of Atrial Septal Defects for Adults: A Pilot Study (Trio-ASD)

Conditions
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Atrial Septal Defect

Intervention / Treatment
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* Device: AMPLATZER™ Septal Occluder.
* Device: Occlutech Figulla Flex II®
* Device: GORE® CARDIOFORM ASD Occluder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years old referred for percutaneous (secundum) ASD closure with right atrial and ventricular enlargement; and clinically significant left-to-tight shunt (Qp:Qs≥1.5:1), or evidence of paradoxical embolism (with a TEE defect >10mm), written informed consent Exclusion Criteria: TEE/CCT/CMR defect diameter >30mm, rim sizes of < 5 mm to the coronary sinus, inferior vena cava rim, an atrioventricular valve, or the right upper pulmonary vein, multiple defects, complex congenital heart disease requiring surgical repair within 3 years of device placement, Eisenmenger-syndrome, recent myocardial infarction PCI/CABG < 6 weeks, demonstrated intra cardiac thrombi on echocardiography (especially LA or LAA thrombi), or atrial tumor known occluded bilateral femoral veins/IVC, pulmonary artery systolic pressure more than half the systemic systolic arterial pressure recent pelvic venous thrombosis serious comorbidity with life expectancy <3 years (e.g., non-skin cancers not in remission, advanced renal failure serum creatinine >160 umol/L) patients whose size or condition would cause the patient to be a poor candidate choice for cardiac catheterization (e.g., too small for echocardiographic imaging probe, catheter size, vascular size, active infection, body weight < 8 kg) serious infection in < 6 weeks producing bacteremia (e.g. sepsis), active endocarditis, or any other infection that cannot be treated successfully prior to device implantation (patient must have negative blood cultures off antibiotics for 1 week prior to procedure), active GI bleed < 6 weeks, bleeding disorder, untreated ulcer, or any other contraindications to aspirin therapy, unless another antiplatelet agent can be administered for 6 months previous stroke in the past 12 months, documented chronic atrial fibrillation or >2 episodes of documented paroxysmal atrial fibrillation in the last 12 months, pregnancy or breastfeeding, plan to become pregnant within the next 6 months, not using an effective method of birth control in premenopausal women, documented nickel/titanium allergy, or intolerance to contrast agents.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 110 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomly assigned to one of three arms for the duration of the study. The arms include: ASO, FSO, GAO/GSO which indicate the type of intervention they will be receiving.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Device: ASO<br>Participants implanted with the AMPLATZER™ Septal Occluder (ASO) | Device: AMPLATZER™ Septal Occluder.<br>* Implantation of the AMPLATZER™ Septal Occluder in the ASD.<br>|
| Active Comparator: Device: FSO<br>Participants implanted with the Occlutech Figulla Flex II® (FSO). | Device: Occlutech Figulla Flex II®<br>* Implantation of the Occlutech Figulla Flex II® in the ASD.<br>|
| Active Comparator: Device: GSO/GAO<br>Participants implanted with the GORE® CARDIOFORM ASD Occluder (GSO/GAO) | Device: GORE® CARDIOFORM ASD Occluder<br>* Implantation of the GORE® CARDIOFORM ASD Occluder or GORE® CARDIOFORM Septal Occluder in the ASD.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite outcome of 'Clinical atrial fibrillation (AF)' or 'Major adverse cerebro-cardiovascular events (MACCE) | At 24 weeks where clinical (AF) includes AF-related, ECG-documented, ED visit/hospitalization/physician visit, cardioversion, ablation or pacemaker implantation or new antiarrhythmic or AF anticoagulant prescription'; MACCE includes 'new onset heart failure (HF), HF-related ED admission, myocardial infarction, stroke, re-intervention, or death. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subclinical AF (SCAF) burden (days): | Days with >6 min of AF detected on CardioSTAT monitor during 14 days | 14 days | 
| Subclinical AF (SCAF) burden (number of episodes): | Number of episodes with >6 min of AF detected on CardioSTAT monitor during 14 days | 14 days | 
| Subclinical AF (SCAF) burden (total time): | Total time in AF during 14 days | 14 days | 
| Subclinical AF (SCAF) burden (percent time): | Percent time in AF during 14 days | 14 days | 
| Procedural effectiveness outcomes (acute technical success rate at discharge) | Successful deployment and retention without major device related complications, stroke, myocardial infarction (MI) or arrhythmia requiring antiarrhythmic drug or cardioversion | Discharge, 24 weeks | 
| Procedural effectiveness outcomes (successful closure rate at discharge): | Negative bubble study or residual shunt <2mm | Discharge, 24 weeks | 
| Patient-reported outcomes (QoL): | Quality of life (QoL) using the EuroQoL (EQ-5D-5L™) at baseline, 6 weeks, 24 weeks | Baseline, 6 weeks, 24 weeks | 
| Patient-reported outcomes (healthcare utilization): | Healthcare utilization (ED admission, physician visit, etc) at 6 and 24 weeks | Baseline, 6 weeks, 24 weeks | 
| Patient-reported outcomes (SF-12): | Quality of life (QoL) using the SF-12 questionnaire at baseline, 6 weeks, 24 weeks | Baseline, 6 weeks, 24 weeks | 
| Patient-reported outcomes (HeartQOL): | Quality of life (QoL) using the HeartQOL questionnaire at baseline, 6 weeks, 24 weeks | Baseline, 6 weeks, 24 weeks | 
| Patient-reported outcomes (satisfaction with device): | Satisfaction with the use of CardioSTAT and KardiaMobile devices using a Likert scale at 24 weeks | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Closure, Transcatheter, Percutaneous, Atrial Septal Defect