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

Paroxysmal Atrial Fibrillation Clinical Trial

— ASAF  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02115100
• Other study ID #: 9206
• Status: Completed
• Phase: N/A
• Start date: March 18, 2014
• Est. completion date: January 19, 2022

Study information

• Verified date: July 2022
• Source: Diagram B.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 145
• Est. completion date: January 19, 2022
• Est. primary completion date: January 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Atrial Fibrillation
• Hypertension
• Out of Range Hypertension
• Paroxysmal Atrial Fibrillation
• Persistent Atrial Fibrillation
• Signs of Sympathetic Overdrive

Intervention

Procedure:
• procedure
Renal ablation+pulmonary vein isolation OR pulmonary vein isolation only

Locations

Country	Name	City	State
Netherlands	MUMC	Maastricht
Netherlands	Radboudumc	Nijmegen
Netherlands	Isala hospital	Zwolle	Overijssel
Spain	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

Sponsors (1)

Lead Sponsor	Collaborator
Diagram B.V.

Countries where clinical trial is conducted

Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to first detection of atrial fibrillation > 30 seconds, with the monitoring period starting 3 months after the intervention.		3 months
Secondary	A-fib burden during follow-up, expressed in % of the monitoring period, in patients with continuous rhythm monitoring.	The monitoring starts after 3 months	12 months
Secondary	Blood pressure after intervention, and change in blood pressure compared to measurement before the intervention		3/6/12 months
Secondary	Blood pressure and heart rate response changes induced by exercise testing		12 months
Secondary	Changes in cardiac sympathetic innervation post-intervention compared to measurement before intervention by MIBG in a subset of patients		12 months
Secondary	Changes in heart rate variability measures tested by Holter monitoring compared to measurements before the intervention		12 months
Secondary	Changes in biomarkers post intervention representing sympathetic tone compared to before the intervention		12 months
Secondary	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		12 months