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…
ID
Source
Brief title
Condition
- Cardiac and vascular disorders congenital
- Vascular therapeutic procedures
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The difference in VO2 max as parameter for exercise capacity between the
interventional and control group.
Secondary outcome
• Technical success
• Complications during the intervention
• Complications after the intervention
• Parameters for exercise capacity
o Peak workload (W and % predicted)
o O2 pulse (ml and % predicted)
o VE/VCO2 slope
• Parameters for RV systolic function
o RVEF (%), measured via CMR
o RV strain (%), measured via speckle tracking echocardiography and CMR
feature tracking
o RV fractional area change (FAC) (%)
o RV pressure on echocardiography (TI gradient)
• Parameters for RV contractility
o RV end systolic elastance (Ees) measured via pressure volume loops
o RV ESV (ml/m2) measured via dobutamine stress CMR
o RVEF (%) measured via dobutamine stress CMR
• Parameters for RV remodeling
• Parameters for RV-PA coupling (invasive in intervention group)
• Lung perfusion (%) measured via MRI
o Left lung perfusion
o Right lung perfusion
• Quality of life
Background summary
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.
Study 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.
Intervention
During this trial, the intervention group will undergo a percutaneous
intervention for branch PA stenosis. This is a standard treatment for branch PA
stenosis according to international guidelines. The research group will have no
influence on the execution of the intervention as it will be performed
according to local practice by experienced interventional cardiologists.
Study burden and risks
The research will be conducted in both children and adults because previous
studies have shown that first reinterventions for residual lesions such as
branch PA stenosis already occur at a median age of 2 years after primary
surgical repair. In addition, previous literature has shown that the majority
of percutaneous branch PA interventions is performed in children which makes
branch PA stenosis mainly a pediatric health care problem. This substantiates
the use of children in this research and shows that our study aims will be of
great importance for all age groups. The risks associated with participation in
the study are negligible for both children and adults because the two
treatments used in this trial (percutaneous intervention for branch PA stenosis
and conservative management) are currently both used in clinical practice for
patients with a class IIa indication for a branch PA intervention. There is no
consensus about the optimal timing for a percutaneous intervention for branch
PA stenosis in international guidelines. Therefore, we will assess both options
in a randomized controlled fashion without any extra risk for the patient. In
addition, the examinations during this study are predominantly non-invasive.
Existing burdens from non-invasive examinations will be minimalized using a
steep RAMP procedure for cardiopulmonary exercise testing and a low dose
dobutamine stress MRI, which has been proven clinically relevant, safe and
effective in patients with congenital heart disease (CHD). Taken together, this
justifies the use of it in this study.
Lundlaan 6
Utrecht 3584 EA
NL
Lundlaan 6
Utrecht 3584 EA
NL
Listed location countries
Age
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
And one or more of the following inclusion criteria (Baumgartner et al. Eur
Heart J 2021; Feltes et al. Circulation 2011; Tatewaki et al. Gen Thorac
Cardiovasc Surg 2018):
• All class IIa indications for a branch PA intervention:
• Persistent decreased RV function (based on gold standard CMR)
o <18 years RVEF <=55% (Van der Ven et al. EHJ Cardiovasc Imaging 2020)
o >=18 years RVEF<50% (Maceira et al. Eur Heart J 2006)
• Progressive tricuspid regurgitation (TR) (>=moderate)
• Bifurcation stenosis
o Significant unilateral stenosis (>=50%)
o 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)
o <18 years (Takken et al. Ann Am Thorac Soc 2017) VO2 peak <35 mL·kg-
1·min-1 (boys)
VO2 peak <30 mL·kg-1·min-1 (girls)
o >=18 years (Kaminsky et al. Mayo Clin Proc 2015) VO2 peak <27 mL·kg-
1·min-1 (men) VO2 peak <19 mL·kg-1·min-1 (women)
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
• All class I indications for a branch PA stenosis intervention:
o Doppler peak gradient >64 mmHg
o Symptoms related to branch PA stenosis
o R-L shunt via ASD or VSD
o Recently developed decreased RV function
• Physical or mental contraindications for at least one of the examinations
(e.g. exercise test, MRI, QoL questionnaire)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL81160.041.22 |