Cardiac Resynchronization Therapy in Adult Congenital Heart Disease With Systemic Right Ventricle: RIGHT-CRT

Study Overview
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Brief Summary
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The main objective of RIGHT-CRT is to assess the impact/efficacy of CRT on functional capacity in ACHD patients with SRV.

Detailed Description
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This study will be the first to bring evidence on CRT efficacy in ACHD patients with heart failure and SRV. If results are positives, CRT may improve functional capacities and quality of life of patients and will become an option of choice in this population. If results are negatives, futile CRT implantation may be avoided in this population in particular considering potential adverse effects and CRT-related complications. Double blind randomized cross-over trial. 40 patients will be enroled. Their follow-up will be 6 months.

Official Title
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Cardiac Resynchronization Therapy in Adult Congenital Heart Disease With Systemic Right Ventricle: A Cross-Over Trial

Conditions
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Congenital Heart Disease, Systemic Right Ventricle, Congenitally Corrected Transposition of the Great Arteries, Transposition of Great Vessels, Heart Failure Congenital

Intervention / Treatment
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* Device: CRT ON (biventricular pacing) / CRT OFF (inactive or univentricular pacing)
* Device: CRT OFF (inactive or univentricular pacing) / CRT ON (biventricular pacing)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: systemic right ventricle (SRV), CRT-P or CRT-D device implanted for at least 1 month, Age ≥18 years old, One of the two following CRT indications: NYHA II-IV, right ventricular ejection fraction ≤ 35% and spontaneous QRS duration ≥ 150 ms Or NYHAI-IV, atrioventricular conduction disorders with ventricular pacing > 40% (regardless right ventricular ejection fraction). Affiliation to a french social security system (beneficiary or legal) Informed and signed consent Exclusion Criteria: Pregnancy or breastfeeding Women of childbearing potential who do not have a negative pregnancy test and do not use one of the following methods of birth control: hormonal contraception or intrauterine device or bilateral tubal occlusion Patient benefiting from a measure of legal protection (guardianship, curatorship, under judicial safeguard, activated future protection mandate and family authorization), Cardiac surgery during the last 3 months or planned during the next 6 months, Percutaneous structural cardiac intervention planned during the next 6 months, Persistent atrial arrhythmia with catheter ablation planned during the next 6 months, Acute congestive heart failure, Dysfunction of at least one CRT device lead that compromise biventricular pacing, Patient on AME Current participation in another interventional clinical study or being in the exclusion period at the end of a previous study.

Ages Eligible for Study
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Minimum Age: 18 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Double blind randomized cross-over trial. Two cross-over periods of 3 months comparing biventricular pacing (CRT ON) vs. inactive pacing (ventricular back-up pacing or left ventricular pacing alone in patients requiring pacing, CRT OFF), each period in random order.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: CRT ON (biventricular pacing) / CRT OFF (inactive or univentricular pacing)<br>Patients with heart failure and SRV and who have a dispositif CRT will be screened for eligibility. If they are eligible and accept to participate (signed informed consent), the order of activation or inactivation of the CRT will be assigned by randomization.Patients randomized into this arm will start the study in CRT ON then CRT OFF mode. | Device: CRT ON (biventricular pacing) / CRT OFF (inactive or univentricular pacing)<br>* Patients randomized to the CRT ON / CRT OFF arm will undergo a first intervention to activate their device and then a second intervention for 3 months to inactivate their device.<br>|
| Other: CRT OFF (inactive or univentricular pacing) / CRT ON (biventricular pacing)<br>Patients with heart failure and SRV and who have a dispositif CRT will be screened for eligibility. If they are eligible and accept to participate (signed informed consent), the order of activation or inactivation of the CRT will be assigned by randomization.Patients randomized into this arm will start the study in CRT OFF then CRT ON mode. | Device: CRT OFF (inactive or univentricular pacing) / CRT ON (biventricular pacing)<br>* Patients randomized to the CRT OFF / CRT ON arm will undergo a first intervention to inactivate their device and then a second intervention for 3 months to activate their device.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-minute walk test | The 6-minute walk test will be performed by a trained technician, indoors, along a long, flat, straight, enclosed corridor with a hard surface and a minimal length of 30 meters. The length of the corridor will be marked every 3 meters and the turnaround points will be marked with a cone. The starting line will be marked on the floor using brightly colored tape. Specific and standardized instructions will be transmitted to the patient. | Change from the end of the first cross over period (3 months) to the end of the second cross over period (6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak oxygen uptake | VO2 max (ml/kg/min) during exercise test with standardized protocol, | Change from the end of the first cross over period (3 months) to the end of the second cross over period (6 months) | 
| NYHA classification | NYHA classification (class I to IV) | Change from the end of the first cross over period (3 months) to the end of the second cross over period (6 months) | 
| Right ventricular ejection fraction | Right ventricular ejection fraction assessed by echocardiography (%) | Change from the end of the first cross over period (3 months) to the end of the second cross over period (6 months) | 
| Tricuspid valve regurgitation | Tricuspid valve regurgitation grade (I to IV) assessed by echocardiography | Change from the end of the first cross over period (3 months) to the end of the second cross over period (6 months) | 
| QRS duration | QRS duration measured on electrocardiogram | Change from the end of the first cross over period (3 months) to the end of the second cross over period (6 months) | 
| Quality of life of patients | Minnesota living with heart failure and SF36v2 questionnaires | Change from the end of the first cross over period (3 months) to the end of the second cross over period (6 months) | 
| BNP | BNP level | Change from the end of the first cross over period (3 months) to the end of the second cross over period (6 months) | 
| Heart failure | Number of hospitalizations for heart failure | Change from the end of the first cross over period (3 months) to the end of the second cross over period (6 months) | 
| Diuretics | Dose of diuretics prescribed | Change from the end of the first cross over period (3 months) to the end of the second cross over period (6 months) | 
| Premature cross-over phase termination | Number of patients with need for premature cross-over phase termination to restore previous pacing settings | Change from the end of the first cross over period (3 months) to the end of the second cross over period (6 months) | 
| Ventricular arrhythmias | Number of non-sustained and sustained ventricular arrhythmias | Change from the end of the first cross over period (3 months) to the end of the second cross over period (6 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cardiac resynchronization therapy, congenital heart disease, systemic right ventricle, heart failure