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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02115100
Recruitment Status : Recruiting
First Posted : April 15, 2014
Last Update Posted : January 10, 2018
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Paroxysmal Atrial Fibrillation Persistent Atrial Fibrillation Out of Range Hypertension Signs of Sympathetic Overdrive Procedure: procedure Not Applicable

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).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 138 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 18, 2014
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: pulmonary vein+renal artery denervation
Procedure: pulmonary vein and renal artery denervation
Procedure: procedure
Renal ablation+pulmonary vein isolation OR pulmonary vein isolation only
Other Name: Renal ablation+pulmonary vein isolation OR pulmonary vein isolation only
Active Comparator: Pulmonary vein isolation
Procedure: Pulmonary vein isolation
Procedure: procedure
Renal ablation+pulmonary vein isolation OR pulmonary vein isolation only
Other Name: Renal ablation+pulmonary vein isolation OR pulmonary vein isolation only

Primary Outcome Measures :
  1. Time to first detection of atrial fibrillation > 30 seconds, with the monitoring period starting 3 months after the intervention. [ Time Frame: 3 months ]

Secondary Outcome Measures :
  1. A-fib burden during follow-up, expressed in % of the monitoring period, in patients with continuous rhythm monitoring. [ Time Frame: 12 months ]
    The monitoring starts after 3 months

  2. Blood pressure after intervention, and change in blood pressure compared to measurement before the intervention [ Time Frame: 3/6/12 months ]
  3. Blood pressure and heart rate response changes induced by exercise testing [ Time Frame: 12 months ]
  4. Changes in cardiac sympathetic innervation post-intervention compared to measurement before intervention by MIBG in a subset of patients [ Time Frame: 12 months ]
  5. Changes in heart rate variability measures tested by Holter monitoring compared to measurements before the intervention [ Time Frame: 12 months ]
  6. Changes in biomarkers post intervention representing sympathetic tone compared to before the intervention [ Time Frame: 12 months ]
  7. 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 [ Time Frame: 12 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02115100

Contact: Arif Evan, MD,PhD 031384244273
Contact: Mark de Jong, MD 031384244273

Isala hospital Recruiting
Zwolle, Overijssel, Netherlands, 8313AB
Contact: Arif Elvan, MD, PhD         
Contact: Mark De Jong, MD         
Hospital Clinic de Barcelona Recruiting
Barcelona, Spain
Contact: Prof. Lluis Mont, MD, PhD         
Contact: Prof. Josep Brugada, MD, PhD         
Hospital Fundación Jimenez Díaz Recruiting
Madrid, Spain
Contact: Borja Ibanez, MD, PhD         
Hospital Puerta de Hierro Recruiting
Madrid, Spain
Contact: Ignacio Fernández Lozano, MD, PhD         
Hospital Universitario 12 de Octubre Recruiting
Madrid, Spain
Contact: F. Arribas, MD, PhD         
Hospital Universitario Virgen de la Victoria Recruiting
Malaga, Spain
Contact: J. Alzueta, MD, PhD         
Hospital Donostia Recruiting
San Sebastián, Spain
Contact: José Manuel Porres, MD, PhD         
Sponsors and Collaborators
Diagram B.V.
Principal Investigator: Arif Elvan, MD, PhD Maatschap Cardiologie Isala

Responsible Party: Diagram B.V. Identifier: NCT02115100     History of Changes
Other Study ID Numbers: 9206
First Posted: April 15, 2014    Key Record Dates
Last Update Posted: January 10, 2018
Last Verified: January 2018

Keywords provided by Diagram B.V.:
Paroxysmal atrial fibrillation
Persistent atrial fibrillation
Out of range hypertension
Signs of sympathetic overdrive

Additional relevant MeSH terms:
Atrial Fibrillation
Vascular Diseases
Cardiovascular Diseases
Arrhythmias, Cardiac
Heart Diseases
Pathologic Processes