Clinical trial NCT05809310: Effects Branch PA Stenting d-TGA, ToF and TA
Official title: The Effects of Branch Pulmonary Artery Stenting in d-TGA, ToF and TA: a Randomized Control Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Transposition of Great Vessels
Tetralogy of Fallot
Truncus Arteriosus
Pulmonary Artery Stenosis Supravalvular Congenital
Stent Stenosis
Right Ventricular Dysfunction
Congenital Heart Disease
Keywords: Exercise capacity
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Dutch Heart Foundation
name: Hartekind
name: Erasmus Medical Center
name: Leiden University Medical Center
name: Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC)
First posted: 2023-04-12
Enrollment: 56
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Change from baseline VO2max as percentage of predicted at 6 months as indication of exercise capacity
timeFrame: change between baseline and 6 months follow-up
Secondary outcomes:
measure: Technical success using invasive right ventricular and pulmonary artery pressures and gradients
timeFrame: after the intervention, an average of 1 month after baseline
measure: Peak workload (W)
timeFrame: at baseline, 6 months follow-up and 2-4 years follow-up
measure: Peak workload (% predicted)
timeFrame: at baseline, 6 months follow-up and 2-4 years follow-up
measure: O2 pulse (ml)
timeFrame: at baseline, 6 months follow-up and 2-4 years follow-up
measure: O2 pulse (% predicted)
timeFrame: at baseline, 6 months follow-up and 2-4 years follow-up
measure: VE/VCO2 slope
timeFrame: at baseline, 6 months follow-up and 2-4 years follow-up
measure: Right ventricular ejection fraction (%)
timeFrame: at baseline, 6 months follow-up and 2-4 years follow-up
measure: RV strain (%)
timeFrame: at baseline, 6 months follow-up and 2-4 years follow-up
measure: RV fractional area change (%)
timeFrame: at baseline, 6 months follow-up and 2-4 years follow-up
measure: RV pressure (mmHg)
timeFrame: at baseline, 6 months follow-up and 2-4 years follow-up
measure: RV end-systolic elastance
timeFrame: before and after the intervention, an average of 1 month after baseline
measure: RV end systolic volume (ml and ml/m2)
timeFrame: at baseline, 6 months follow-up and 2-4 years follow-up
measure: RV end diastolic volume (ml and ml/m2)
timeFrame: at baseline, 6 months follow-up and 2-4 years follow-up
measure: RV functional reserve
timeFrame: at baseline and 6 months follow-up in the interventional group from UMC Utrecht and Erasmus MC
measure: RV mass (g and g/m2)
timeFrame: at baseline, 6 months follow-up and 2-4 years follow-up
measure: Right ventricular pulmonary arterial (RV-PA) coupling
timeFrame: before and after the intervention, an average of 1 month after baseline
measure: Lung perfusion (%)
timeFrame: at baseline, 6 months follow-up and 2-4 years follow-up
measure: Quality of Life (QoL) in 4 domains: health and related activities, emotional, social and school/work
timeFrame: at baseline and 2 weeks follow-up
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam University Medical Center location AMC
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Utrecht
country: Netherlands
facility: UMC Utrecht/WKZ
Study officials:
References: