Effects Branch PA Stenting d-TGA, ToF and TA

Study Overview
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Brief Summary
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The goal of this randomized controlled trial is to identify the effects of percutaneous interventions for branch PA stenosis on exercise capacity in patients with d-TGA, ToF and TA. The main question[s] it aims to answer are: The primary study objective is to identify the effects of percutaneous interventions for branch PA stenosis on exercise capacity in patients with d-TGA, ToF and TA. The secondary objectives are 1) to assess the effects of percutaneous interventions for branch PA stenosis on RV function and 2) to define early markers for RV function and adaptation to improve timing of these interventions. Participants will undergo the same series of examinations at baseline and approximately 6 months follow-up (within 6 week time-range) as part of standard care: conventional transthoracic echocardiogram (TTE), cardiopulmonary exercise testing (CPET) and conventional Cardiac Magnetic Resonance (CMR) including a low dose dobutamine stress MRI to assess RV functional reserve. The low dose dobutamine stress MRI will be performed in the interventional group from the UMC Utrecht/WKZ and Erasmus MC because the LUMC and AUMC do not have a suitable infrastructure for the low dose dobutamine stress MRI and this cannot be achieved throughout the duration of this study. The baseline CMR in the interventional group will be performed as close as possible prior to the intervention but maximal 4 weeks prior to the intervention. In addition, the intervention group will undergo standard RV pressure measurements during the intervention. Quality of life (QoL) questionnaires will be obtained at baseline and 2 weeks post intervention (intervention group) or a similar time range in the control group, which is based on experts opinion. TTE, CPET and conventional CMR will be performed within 2-4 years follow-up to assess the long-term effects of percutaneous PA interventions. Researchers will compare the difference in VO2 max (% predicted) between the interventional group (TGA, ToF or TA patients with a class II indication for a PA intervention who will undergo a percutaneous intervention for a PA stenosis) and the control group (TGA, ToF or TA patients with a class II indication for a PA intervention who will undergo conservative management)

Detailed Description
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Rationale: Postoperative survival of patients with dextro transposition of the great arteries (d-TGA), Tetralogy of Fallot (ToF) and Truncus Arteriosus (TA) has increased over the last decades due to advances in operative techniques and perioperative care. Despite postoperative survival has increased, morbidity of these patients increases during long-term follow-up with a high need for reinterventions. Right ventricular outflow tract (RVOT) obstructions are the most common indication for a reintervention and percutaneous branch pulmonary artery (PA) interventions account for a significant number of these reinterventions. However, the effects of percutaneous branch PA interventions on exercise capacity, RV function and RV adaptation of patients with d-TGA, ToF and TA remains largely unknown. In addition, there is no consensus about the optimal timing for percutaneous interventions for branch PA stenosis in international guidelines. Objective: The primary study objective is to identify the effects of percutaneous interventions for branch PA stenosis on exercise capacity in patients with d-TGA, ToF and TA. The secondary objectives are 1) to assess the effects of percutaneous interventions for branch PA stenosis on RV function and 2) to define early markers for RV function and adaptation to improve timing of these interventions. Study design: This is a multicenter randomized controlled trial. Patients will be included from the following Dutch interventional centers for congenital heart disease: UMC Utrecht/WKZ (sponsor), LUMC/AUMC and Erasmus MC. During this trial there will be two groups: 1. a group of patients with d-TGA, ToF and TA who will undergo a percutaneous intervention for a branch PA stenosis according to standard care (intervention group) and 2. a group of patients with d-TGA, ToF and TA with a similar degree of pulmonary stenosis as group 1 (class IIa indication) who will undergo conservative management for a branch PA stenosis according to standard care (control group). If necessary, the control group will be able to undergo a percutaneous intervention for branch PA stenosis after the examinations at approximately 6 months follow-up, or sooner in case of symptoms. Patients from both groups will undergo the same series of examinations at baseline and approximately 6 months follow-up (within 6 week time-range) as part of standard care: conventional transthoracic echocardiogram (TTE), cardiopulmonary exercise testing (CPET) and conventional Cardiac Magnetic Resonance (CMR) including a low dose dobutamine stress MRI to assess RV functional reserve. The low dose dobutamine stress MRI will be performed in the interventional group from the UMC Utrecht/WKZ and Erasmus MC because the LUMC and AUMC do not have a suitable infrastructure for the low dose dobutamine stress MRI and this cannot be achieved throughout the duration of this study. The baseline CMR in the interventional group will be performed as close as possible prior to the intervention but maximal 4 weeks prior to the intervention. In addition, the intervention group will undergo standard RV pressure measurements during the intervention. Quality of life (QoL) questionnaires will be obtained at baseline and 2 weeks post intervention (intervention group) or a similar time range in the control group, which is based on experts opinion. TTE, CPET and conventional CMR will be performed within 2-4 years follow-up to assess the long-term effects of percutaneous PA interventions. Study population: d-TGA post ASO, ToF or TA patients ≥8 years old will be included if they have a class IIa indication for a percutaneous intervention for branch PA stenosis according to the international guidelines. Patients will be excluded if they contraindications for one of the examinations. Main study parameters/endpoints: the difference in VO2 max (% predicted) as parameter for exercise capacity between the interventional and control group.

Official Title
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The Effects of Branch Pulmonary Artery Stenting in d-TGA, ToF and TA: a Randomized Control Trial

Conditions
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Transposition of Great Vessels, Tetralogy of Fallot, Truncus Arteriosus, Pulmonary Artery Stenosis Supravalvular Congenital, Stent Stenosis, Right Ventricular Dysfunction, Congenital Heart Disease

Intervention / Treatment
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* Procedure: Percutaneous intervention (stent) for PA stenosis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria: Patients with d-TGA post ASO, ToF or TA ≥8 years Exclusion Criteria: One or more of the following inclusion criteria: All class IIa indications for a branch PA intervention: Persistent decreased RV function (based on gold standard CMR) <18 years RVEF ≤55% (28) ≥18 years RVEF<50% (29) Progressive tricuspid regurgitation (TR) (≥moderate) Isolated bifurcation stenosis: Significant unilateral stenosis (≥50%) Borderline bilateral PA stenosis (40-70%) Unbalanced perfusion (≤35/65%) RV/LV pressure ratio > 2/3 based on echocardiography Reduced lung perfusion or decreased objective exercise capacity (based of gold standard VO2 max during CPET) <18 years VO2 peak <35 mL∙kg-1∙min-1 (boys) VO2 peak <30 mL∙kg-1∙min-1 (girls) (30) ≥18 years VO2 peak <27 mL∙kg-1∙min-1 (men) VO2 peak <19 mL∙kg-1∙min-1 (women) (31)

Ages Eligible for Study
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Minimum Age: 8 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Interventional group<br>Percutaneous intervention for PA stenosis | Procedure: Percutaneous intervention (stent) for PA stenosis<br>* Percutaneous intervention (stent placement) in one or both of the branch pulmonary arteries<br>|
| No Intervention: Control group<br>Conservative management (percutaneous intervention for PA stenosis 6 months postponed) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline VO2max as percentage of predicted at 6 months as indication of exercise capacity | using cardiopulmonary exercise test on a treadmill | change between baseline and 6 months follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Technical success using invasive right ventricular and pulmonary artery pressures and gradients | Technical success of the intervention using invasive right ventricular and pulmonary artery pressures and gradients | after the intervention, an average of 1 month after baseline | 
| Peak workload (W) | using cardiopulmonary exercise test on a treadmill | at baseline, 6 months follow-up and 2-4 years follow-up | 
| Peak workload (% predicted) | using cardiopulmonary exercise test on a treadmill | at baseline, 6 months follow-up and 2-4 years follow-up | 
| O2 pulse (ml) | using cardiopulmonary exercise test on a treadmill | at baseline, 6 months follow-up and 2-4 years follow-up | 
| O2 pulse (% predicted) | using cardiopulmonary exercise test on a treadmill | at baseline, 6 months follow-up and 2-4 years follow-up | 
| VE/VCO2 slope | using cardiopulmonary exercise test on a treadmill | at baseline, 6 months follow-up and 2-4 years follow-up | 
| Right ventricular ejection fraction (%) | using CMR | at baseline, 6 months follow-up and 2-4 years follow-up | 
| RV strain (%) | using speckle tracking echocardiography and CMR feature tracking | at baseline, 6 months follow-up and 2-4 years follow-up | 
| RV fractional area change (%) | using echocardiography | at baseline, 6 months follow-up and 2-4 years follow-up | 
| RV pressure (mmHg) | using echocardiography (TI gradient) | at baseline, 6 months follow-up and 2-4 years follow-up | 
| RV end-systolic elastance | using pressure-volume analysis | before and after the intervention, an average of 1 month after baseline | 
| RV end systolic volume (ml and ml/m2) | using CMR | at baseline, 6 months follow-up and 2-4 years follow-up | 
| RV end diastolic volume (ml and ml/m2) | using CMR | at baseline, 6 months follow-up and 2-4 years follow-up | 
| RV functional reserve | RVEF dobutamine - RVEF rest using a low dose dobutamine stress MRI | at baseline and 6 months follow-up in the interventional group from UMC Utrecht and Erasmus MC | 
| RV mass (g and g/m2) | using CMR | at baseline, 6 months follow-up and 2-4 years follow-up | 
| Right ventricular pulmonary arterial (RV-PA) coupling | using pressure-volume analysis | before and after the intervention, an average of 1 month after baseline | 
| Lung perfusion (%) | using CMR | at baseline, 6 months follow-up and 2-4 years follow-up | 
| Quality of Life (QoL) in 4 domains: health and related activities, emotional, social and school/work | using PedsQL questionnaire | at baseline and 2 weeks follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exercise capacity