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Treatment of Atrial Fibrillation in Patients by Pulmonary Vein Isolation in Combination With Renal Denervation or Pulmonary Vein Isolation Only

Not Applicable
Completed
Conditions
Persistent Atrial Fibrillation
Signs of Sympathetic Overdrive
Paroxysmal Atrial Fibrillation
Out of Range Hypertension
Registration Number
NCT02115100
Lead Sponsor
Diagram B.V.
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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
145
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Primary Outcome Measures
NameTimeMethod
Time to first detection of atrial fibrillation > 30 seconds, with the monitoring period starting 3 months after the intervention.3 months
Secondary Outcome Measures
NameTimeMethod
A-fib burden during follow-up, expressed in % of the monitoring period, in patients with continuous rhythm monitoring.12 months

The monitoring starts after 3 months

Blood pressure after intervention, and change in blood pressure compared to measurement before the intervention3/6/12 months
Changes in heart rate variability measures tested by Holter monitoring compared to measurements before the intervention12 months
Blood pressure and heart rate response changes induced by exercise testing12 months
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 intervention12 months
Changes in cardiac sympathetic innervation post-intervention compared to measurement before intervention by MIBG in a subset of patients12 months
Changes in biomarkers post intervention representing sympathetic tone compared to before the intervention12 months

Trial Locations

Locations (8)

Isala hospital

🇳🇱

Zwolle, Overijssel, Netherlands

MUMC

🇳🇱

Maastricht, Netherlands

Radboudumc

🇳🇱

Nijmegen, Netherlands

Hospital Clinic de Barcelona

🇪🇸

Barcelona, Spain

Hospital Fundación Jimenez Díaz

🇪🇸

Madrid, Spain

Hospital Puerta de Hierro

🇪🇸

Madrid, Spain

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Hospital Universitario Virgen de la Victoria

🇪🇸

Malaga, Spain

Isala hospital
🇳🇱Zwolle, Overijssel, Netherlands

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