Effects Branch PA Stenting d-TGA, ToF and TA

Congenital Heart Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05809310
• Other study ID #: NL81160
• Status: Recruiting
• Phase: N/A
• Start date: April 18, 2023
• Est. completion date: September 30, 2025

Study information

• Verified date: May 2023
• Source: UMC Utrecht
• Contact: Hans Breur, MD, PhD
• Phone: +31 88 75 754 59
• Email: h.breur[@]umcutrecht.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 56
• Est. completion date: September 30, 2025
• Est. primary completion date: September 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Congenital Heart Disease
• Constriction, Pathologic
• Heart Defects, Congenital
• Right Ventricular Dysfunction
• Stent Stenosis
• Tetralogy of Fallot
• Transposition of Great Vessels
• Truncus Arteriosus
• Truncus Arteriosus, Persistent
• Ventricular Dysfunction
• Ventricular Dysfunction, Right

Intervention

Procedure:
• Percutaneous intervention (stent) for PA stenosis
Percutaneous intervention (stent placement) in one or both of the branch pulmonary arteries

Locations

Country	Name	City	State
Netherlands	Amsterdam University Medical Center location AMC	Amsterdam
Netherlands	Leiden University Medical Center	Leiden
Netherlands	Erasmus Medical Center	Rotterdam
Netherlands	UMC Utrecht/WKZ	Utrecht

Sponsors (6)

Lead Sponsor	Collaborator
UMC Utrecht	Amsterdam University Medical Centers (UMC), Location Academic Medical Center (AMC), Dutch Heart Foundation, Erasmus Medical Center, Hartekind, Leiden University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Peak workload (W)	using cardiopulmonary exercise test on a treadmill	at baseline, 6 months follow-up and 2-4 years follow-up
Secondary	Peak workload (% predicted)	using cardiopulmonary exercise test on a treadmill	at baseline, 6 months follow-up and 2-4 years follow-up
Secondary	O2 pulse (ml)	using cardiopulmonary exercise test on a treadmill	at baseline, 6 months follow-up and 2-4 years follow-up
Secondary	O2 pulse (% predicted)	using cardiopulmonary exercise test on a treadmill	at baseline, 6 months follow-up and 2-4 years follow-up
Secondary	VE/VCO2 slope	using cardiopulmonary exercise test on a treadmill	at baseline, 6 months follow-up and 2-4 years follow-up
Secondary	Right ventricular ejection fraction (%)	using CMR	at baseline, 6 months follow-up and 2-4 years follow-up
Secondary	RV strain (%)	using speckle tracking echocardiography and CMR feature tracking	at baseline, 6 months follow-up and 2-4 years follow-up
Secondary	RV fractional area change (%)	using echocardiography	at baseline, 6 months follow-up and 2-4 years follow-up
Secondary	RV pressure (mmHg)	using echocardiography (TI gradient)	at baseline, 6 months follow-up and 2-4 years follow-up
Secondary	RV end-systolic elastance	using pressure-volume analysis	before and after the intervention, an average of 1 month after baseline
Secondary	RV end systolic volume (ml and ml/m2)	using CMR	at baseline, 6 months follow-up and 2-4 years follow-up
Secondary	RV end diastolic volume (ml and ml/m2)	using CMR	at baseline, 6 months follow-up and 2-4 years follow-up
Secondary	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
Secondary	RV mass (g and g/m2)	using CMR	at baseline, 6 months follow-up and 2-4 years follow-up
Secondary	Right ventricular pulmonary arterial (RV-PA) coupling	using pressure-volume analysis	before and after the intervention, an average of 1 month after baseline
Secondary	Lung perfusion (%)	using CMR	at baseline, 6 months follow-up and 2-4 years follow-up
Secondary	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