Clinical trial NCT02115100: Treatment of Atrial Fibrillation in Patients by Pulmonary Vein Isolation in Combination With Renal Denervation or Pulmonary Vein Isolation Only
Official title: Treatment of Atrial Fibrillation in Patients With High Sympathetic Activity by Pulmonary Vein Isolation in Combination With Renal Denervation or Pulmonary Vein Isolation Only; an International Randomized, Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Paroxysmal Atrial Fibrillation
Persistent Atrial Fibrillation
Out of Range Hypertension
Signs of Sympathetic Overdrive
Keywords: Paroxysmal atrial fibrillation
Persistent atrial fibrillation
Out of range hypertension
Signs of sympathetic overdrive
Lead sponsor: Diagram B.V.
Sponsor class: OTHER
First posted: 2014-04-15
Enrollment: 145
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Prospective, randomized, controlled, multicenter, international clinical trial. The study population consist of patients with paroxysmal or persistent atrial fibrillation with out range hypertension or signs of sympathetic overdrive. Patient will be randomized into one of the following two groups.

group 1 : patients will undergo pulmonary vein isolation, group 2: Patients will undergo pulmonary vein isolation and renal artery denervation.

Detailed description: The target group of patients are subjects ages \<65 years, with paroxysmal or persistent atrial fibrillation, who have out of range hypertension (systolic \>140 mmHg or \>130/80 mmHg in diabetics and patients with chronic renal disease) or signs of sympathetic overdrive. Patients should use at least 2 anti-hypertensive's or should be intolerant for antihypertensive medication.

Atrial fibrillation terminology: If atrial fibrillation recurs more than once but terminates spontaneously within seven days, the term paroxysmal AF is used. This is also used when the episode is less than 48 hours in duration and is terminated with electrical or pharmacological cardioversion. Persistent AF is defined as recurrent AF that is sustained for more than seven days. A patient that is electrically or pharmacologically cardioverted after more than two days is also diagnosed with persistent AF.

After the exclusion of apparent secondary causes of hypertension, patients will be randomized to one of the following interventional treatments:

First arm: PVI (69 patients) Second arm: PVI + RDN (69 patients)

The patient will be treated under conscious sedation or general anesthesia. The control group will consist of patients who undergo PVI alone. The study will be a randomized, controlled trial. The follow up period will be up to one year after the interventional therapy. Patients will be treated clinically and will have regular follow-up at the outpatient clinic of the hospital at which they were treated. If patients receive continuous loop recorders for cardiac rhythm monitoring, this data will be used for the study. The other patients will undergo Holter ECG monitoring at regular intervals during follow-up (at 3, 6 and 12 months after the interventional treatment). During follow-up, the first 3 months after the interventional treatment will be a blanking period, as is common in the ablative therapy of AF (ablations points need to heal, and paroxysms of AF in this period are not associated with therapy failure).

Eligibility criteria: Inclusion Criteria:

1. The patient is willing and able to comply with the protocol and has provided written informed consent.
2. The patient falls within the target group resistant hypertension or sympathetic overdrive
3. Patient is an acceptable candidate for renal denervation treatment
4. Patient is \< 65 year of age

Exclusion Criteria:

1. Documented left atrial diameter on trans thoracic echocardiography (PLAX \> 4.5 cm).
2. Contraindication to chronic anticoagulation therapy or heparin.
3. Previous left heart ablation procedure for AF (atrial fibrillation).
4. Acute coronary syndrome, cardiac surgery, PCI (percutaneous coronary intervention)or stroke within 3 months prior to enrollment.
5. Untreated hypothyroidism or hyperthyroidism.
6. More than grade 1/3 valvular regurgitation and/or significant valve stenosis (modest or severe).
7. LVEF (Left ventricular function) \<45% and/or grade 3/4 diastolic dysfunction.
8. Enrollment in another investigational drug or device study.
9. Woman currently pregnant or breastfeeding or not using reliable contraceptive measures during fertile age.
10. Mental or physical inability to participate in the study.
11. Planned cardiovascular intervention.
12. Life expectancy ≤ 12 months.
13. Renal artery stenosis \>50% of the arterial lumen, or renal artery lumen

    ≤3 mm.
14. Dual or triple ipsilateral renal artery ostia.
15. Obvious secondary cause of hypertension.

Primary outcomes:
measure: Time to first detection of atrial fibrillation > 30 seconds, with the monitoring period starting 3 months after the intervention.
timeFrame: 3 months
Secondary outcomes:
measure: A-fib burden during follow-up, expressed in % of the monitoring period, in patients with continuous rhythm monitoring.
timeFrame: 12 months
measure: Blood pressure after intervention, and change in blood pressure compared to measurement before the intervention
timeFrame: 3/6/12 months
measure: Blood pressure and heart rate response changes induced by exercise testing
timeFrame: 12 months
measure: Changes in cardiac sympathetic innervation post-intervention compared to measurement before intervention by MIBG in a subset of patients
timeFrame: 12 months
measure: Changes in heart rate variability measures tested by Holter monitoring compared to measurements before the intervention
timeFrame: 12 months
measure: Changes in biomarkers post intervention representing sympathetic tone compared to before the intervention
timeFrame: 12 months
measure: Changes in arterial stiffness measures post intervention ambulatory arterial stiffness index by ambulatory blood pressure monitoring, pulse wave velocity and augmentation index compared to measurement before the intervention
timeFrame: 12 months
Other outcomes:
Locations:
city: Zwolle
country: Netherlands
facility: Isala hospital
state: Overijssel
city: Maastricht
country: Netherlands
facility: MUMC
city: Nijmegen
country: Netherlands
facility: Radboudumc
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Madrid
country: Spain
facility: Hospital Fundación Jimenez Díaz
city: Madrid
country: Spain
facility: Hospital Puerta de Hierro
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
Study officials:
affiliation: Maatschap Cardiologie Isala
name: Arif Elvan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Younis A, Steinberg JS. Renal Denervation for Patients With Atrial Fibrillation. Curr Cardiol Rep. 2021 Jul 16;23(9):126. doi: 10.1007/s11886-021-01558-4.