Atrial Fibrillation, Uncontrolled Hypertension
Conditions
Keywords
renal sympathetic denervation, renal catheter ablation, hypertension
Brief summary
The objective of the H-FIB trial is to determine the role of renal sympathetic denervation in the prevention of Atrial Fibrillation (AF) recurrence in patients with hypertension for whom a catheter-based AF ablation procedure is planned. Patients will be randomized to either AF catheter ablation (usual therapy) or AF catheter ablation plus renal sympathetic denervation.
Detailed description
The purpose of this study is to examine the potential additional benefit of performing renal sympathetic denervation at the same time as an AF ablation procedure, in order to improve the long-term success of the AF procedure. To take part in this study, you must meet all study requirements. Screening visit tests and procedures such as a physical exam, blood pressure, review of medical history, blood sample, and a Transthoracic Echocardiogram (TTE) are done to see if you are eligible to be in the study. Patients who qualify for the study and provide consent will undergo catheter ablation for AF. Very thin electrode catheters, similar to long wires, will be inserted into blood vessels in the groin. Using the ablation catheter, we will ablate or damage the tissue adjacent to your pulmonary veins that is not behaving normally. Immediately following the catheter ablation, patients will undergo a renal angiogram in order to assess suitability for catheter-based renal sympathetic denervation. A renal angiogram is an x-ray study of the blood vessels in the kidney to evaluate for blockage, and abnormalities that could be affecting the blood supply to the kidney. It is performed by injecting contrast dye through a catheter (a tiny tube) into the blood vessels of the kidney.
Interventions
Renal sympathetic denervation is modulation of the nerves which run along the renal arteries (the renal sympathetic nerves) with radiofrequency energy. This is the same energy source used to perform your heart ablation. Boston Scientific Vessix Renal Denervation System, Boston Scientific, Inc., Quincy, Massachusetts
Sponsors
Vivek Reddy
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Inclusion Criteria * Age ≥ 18 years of age * History of AF (paroxysmal or persistent) and planned for a guideline-supported catheter ablation procedure * History of significant hypertension (defined as SBP ≥160 mm Hg and/or DBP ≥100 mmHg) and receiving treatment with at least one anti-hypertensive medication OR Clinical History of hypertension and receiving treatment with at least two anti-hypertensive medications (specifically for blood pressure reduction). * Renal vasculature is accessible as determined by intra-procedural renal angiography. * Ability to understand the requirements of the study * Willingness to adhere to study restrictions, comply with all post-procedural follow-up requirements and to sign informed consent
Exclusion criteria
* Inability to undergo AF catheter ablation (e.g., presence of a left atrial thrombus, contraindication to all anticoagulation) * Prior left atrial ablation for an atrial arrhythmia (before this index procedure) * Patients with NYHA class IV congestive heart failure * Individual has known secondary hypertension * Individual has renal artery anatomy that is ineligible for treatment including: 1. Inability to access renal vasculature 2. Main renal arteries \< 3 mm in diameter or \< 20 mm in length. 3. Hemodynamically or anatomically significant renal artery abnormality or stenosis in either renal artery which, in the eyes of the operator, would interfere with safe cannulation of the renal artery or meets standards for surgical repair or interventional dilation. 4. A history of prior renal artery intervention including balloon angioplasty or stenting that precludes a possibility of ablation treatment. * Individual has an estimated glomerular filtration rate (eGFR) of less than 45mL/min/1.73m2, using the MDRD calculation. * Individual has a single functioning kidney (either congenitally or iatrogenically). * Individual is pregnant or nursing. * Life expectancy \<1 year for any medical condition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Anti-arrhythmic Drug (AAD)-Free Single-procedure Freedom From Atrial Fibrillation Recurrence | up to 12 months | The primary endpoint of this study is anti-arrhythmic drug (AAD)-free single-procedure freedom from AF recurrence through 12 months (not including a 90 day blanking period). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Freedom From AF Recurrence Despite Taking AADs | up to 24 months | Freedom from AF recurrence through 24 months (not-including the pre-defined 90 day blanking period) despite taking AADs |
| Blood Pressure Control as Compared to Baseline | baseline, 6 months, 12 months, and 24 months | Blood pressure control between the two groups as compared to baseline at 6 months, 12 months and 24 months. |
| Number of Participants With Major Adverse Cardiac Events (MACE) | within 12 months of randomization | Number of Participants with Major adverse cardiac events (MACE) defined as a non-weighted composite score of: death, stroke, CHF hospitalization, and clinically diagnosed thromboembolic events other than stroke and hemorrhage requiring transfusion within 12 months of randomization |
| Number of Participants With Serious Adverse Events (SAE) | up to 24 months | SAE-any experience that results in a fatality or is life threatening; results in significant or persistent disability; requires or prolongs hospitalization; results in congenital anomaly/birth defect; or represents other significant hazards or potentially serious harm to research subjects or others, in the opinion of the investigators. Important medical events that may not result in above may be considered a SAE when, based upon appropriate medical judgment, they may jeopardize the patient and may require medical or surgical intervention to prevent one of the outcomes listed in this definition |
| AAD-free Single-procedure Freedom From AF Recurrence | up to 24 months | AAD-free single-procedure freedom from AF recurrence through 24 months (not-including recurrences within the first 90 days of the initial ablation procedure) |
| Ejection Fraction (EF) | at baseline and at 12 months | Ejection fraction (EF) is a measurement, expressed as a percentage, of how much blood the left ventricle pumps out with each contraction. A normal heart's ejection fraction may be between 50 and 70 percent. |
| Number of Participants With Procedure Adverse Events | up to 24 months | Causality will be defined as adverse events that, after careful medical evaluation, are considered with a high degree of certainty to be related to the intervention (AF ablation ± renal sympathetic denervation). |
| Number of Anti-hypertensive Medications | baseline and 24 months | Total number of anti-hypertensive medications at study end, compared between the two treatment arms |
| Atrial Fibrillation Effect on QualiTy-of-life Questionnaire (AFEQT) | baseline, 12 months and 24 months | The change in quality of life (QoL) from baseline to 12 months as measured by AFEQT, a 20- item instrument. Full range from 0 to 100, with higher score indicates higher level of QoL. |
| Left Atrial (LA) Size | at baseline and at 12 months | LA size by TTE at baseline and at 12 months |
Countries
Czechia, Russia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Renal Sympathetic Denervation PLUS Catheter Ablation Routine catheter ablation of atrial fibrillation PLUS renal sympathetic denervation with the Boston Scientific Vessix Renal Denervation System.
Boston Scientific Vessix Renal Denervation System: Renal sympathetic denervation is modulation of the nerves which run along the renal arteries (the renal sympathetic nerves) with radiofrequency energy. This is the same energy source used to perform your heart ablation. | 28 |
| Routine Catheter Abation Routine catheter ablation of atrial fibrillation only. | 22 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 1 |
| Overall Study | Lost to Follow-up | 2 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 5 |
Baseline characteristics
| Characteristic | Renal Sympathetic Denervation PLUS Catheter Ablation | Routine Catheter Abation | Total |
|---|---|---|---|
| Age, Continuous | 64.4 years STANDARD_DEVIATION 6.9 | 65.3 years STANDARD_DEVIATION 8.2 | 65.17 years STANDARD_DEVIATION 7.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 22 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 28 Participants | 22 Participants | 50 Participants |
| Sex: Female, Male Female | 12 Participants | 8 Participants | 20 Participants |
| Sex: Female, Male Male | 16 Participants | 14 Participants | 30 Participants |
| Type of Atrial Fibrillation (AF) Paroxysmal AF | 20 Participants | 15 Participants | 35 Participants |
| Type of Atrial Fibrillation (AF) Persistent AF | 8 Participants | 7 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 28 | 1 / 22 |
| other Total, other adverse events | 6 / 28 | 5 / 22 |
| serious Total, serious adverse events | 12 / 28 | 4 / 22 |
Outcome results
Primary
Anti-arrhythmic Drug (AAD)-Free Single-procedure Freedom From Atrial Fibrillation Recurrence
The primary endpoint of this study is anti-arrhythmic drug (AAD)-free single-procedure freedom from AF recurrence through 12 months (not including a 90 day blanking period).
Time frame: up to 12 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Renal Sympathetic Denervation PLUS Catheter Ablation | Anti-arrhythmic Drug (AAD)-Free Single-procedure Freedom From Atrial Fibrillation Recurrence | 6 recurrences |
| Routine Catheter Abation | Anti-arrhythmic Drug (AAD)-Free Single-procedure Freedom From Atrial Fibrillation Recurrence | 2 recurrences |
Secondary
AAD-free Single-procedure Freedom From AF Recurrence
AAD-free single-procedure freedom from AF recurrence through 24 months (not-including recurrences within the first 90 days of the initial ablation procedure)
Time frame: up to 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Renal Sympathetic Denervation PLUS Catheter Ablation | AAD-free Single-procedure Freedom From AF Recurrence | 7 recurrences |
| Routine Catheter Abation | AAD-free Single-procedure Freedom From AF Recurrence | 6 recurrences |
Secondary
Atrial Fibrillation Effect on QualiTy-of-life Questionnaire (AFEQT)
The change in quality of life (QoL) from baseline to 12 months as measured by AFEQT, a 20- item instrument. Full range from 0 to 100, with higher score indicates higher level of QoL.
Time frame: baseline, 12 months and 24 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Renal Sympathetic Denervation PLUS Catheter Ablation | Atrial Fibrillation Effect on QualiTy-of-life Questionnaire (AFEQT) | Baseline | 72.75 score on a scale | Standard Deviation 22.85 |
| Renal Sympathetic Denervation PLUS Catheter Ablation | Atrial Fibrillation Effect on QualiTy-of-life Questionnaire (AFEQT) | 12 months | 37.95 score on a scale | Standard Deviation 16.13 |
| Renal Sympathetic Denervation PLUS Catheter Ablation | Atrial Fibrillation Effect on QualiTy-of-life Questionnaire (AFEQT) | 24 months | 39.8 score on a scale | Standard Deviation 20.32 |
| Routine Catheter Abation | Atrial Fibrillation Effect on QualiTy-of-life Questionnaire (AFEQT) | Baseline | 75.4 score on a scale | Standard Deviation 26.54 |
| Routine Catheter Abation | Atrial Fibrillation Effect on QualiTy-of-life Questionnaire (AFEQT) | 12 months | 30 score on a scale | Standard Deviation 11.58 |
| Routine Catheter Abation | Atrial Fibrillation Effect on QualiTy-of-life Questionnaire (AFEQT) | 24 months | 36.57 score on a scale | Standard Deviation 21.1 |
Secondary
Blood Pressure Control as Compared to Baseline
Blood pressure control between the two groups as compared to baseline at 6 months, 12 months and 24 months.
Time frame: baseline, 6 months, 12 months, and 24 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Renal Sympathetic Denervation PLUS Catheter Ablation | Blood Pressure Control as Compared to Baseline | Systolic Baseline | 146.6 mmHg | Standard Deviation 20.6 |
| Renal Sympathetic Denervation PLUS Catheter Ablation | Blood Pressure Control as Compared to Baseline | Diastolic Baseline | 81.46 mmHg | Standard Deviation 13.4 |
| Renal Sympathetic Denervation PLUS Catheter Ablation | Blood Pressure Control as Compared to Baseline | Systolic 12 months | 137.88 mmHg | Standard Deviation 17.55 |
| Renal Sympathetic Denervation PLUS Catheter Ablation | Blood Pressure Control as Compared to Baseline | Diastolic 6 months | 80.88 mmHg | Standard Deviation 10.08 |
| Renal Sympathetic Denervation PLUS Catheter Ablation | Blood Pressure Control as Compared to Baseline | Diastolic 12 months | 82.36 mmHg | Standard Deviation 9.19 |
| Renal Sympathetic Denervation PLUS Catheter Ablation | Blood Pressure Control as Compared to Baseline | Systolic 6 months | 136.88 mmHg | Standard Deviation 17.36 |
| Renal Sympathetic Denervation PLUS Catheter Ablation | Blood Pressure Control as Compared to Baseline | Diastolic 24 months | 79.8 mmHg | Standard Deviation 7.48 |
| Renal Sympathetic Denervation PLUS Catheter Ablation | Blood Pressure Control as Compared to Baseline | Systolic 24 months | 133.88 mmHg | Standard Deviation 14.4 |
| Routine Catheter Abation | Blood Pressure Control as Compared to Baseline | Diastolic 24 months | 78.87 mmHg | Standard Deviation 9.75 |
| Routine Catheter Abation | Blood Pressure Control as Compared to Baseline | Systolic Baseline | 143.45 mmHg | Standard Deviation 18.47 |
| Routine Catheter Abation | Blood Pressure Control as Compared to Baseline | Systolic 6 months | 142.06 mmHg | Standard Deviation 78.94 |
| Routine Catheter Abation | Blood Pressure Control as Compared to Baseline | Systolic 12 months | 144.53 mmHg | Standard Deviation 21.6 |
| Routine Catheter Abation | Blood Pressure Control as Compared to Baseline | Systolic 24 months | 138.7 mmHg | Standard Deviation 19.9 |
| Routine Catheter Abation | Blood Pressure Control as Compared to Baseline | Diastolic Baseline | 79.18 mmHg | Standard Deviation 12.45 |
| Routine Catheter Abation | Blood Pressure Control as Compared to Baseline | Diastolic 12 months | 82.03 mmHg | Standard Deviation 6.6 |
| Routine Catheter Abation | Blood Pressure Control as Compared to Baseline | Diastolic 6 months | 78.94 mmHg | Standard Deviation 7.8 |
Secondary
Ejection Fraction (EF)
Ejection fraction (EF) is a measurement, expressed as a percentage, of how much blood the left ventricle pumps out with each contraction. A normal heart's ejection fraction may be between 50 and 70 percent.
Time frame: at baseline and at 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Renal Sympathetic Denervation PLUS Catheter Ablation | Ejection Fraction (EF) | Baseline | 62.52 percent of blood | Standard Deviation 6.88 |
| Renal Sympathetic Denervation PLUS Catheter Ablation | Ejection Fraction (EF) | 12 months | 62.9 percent of blood | Standard Deviation 7.21 |
| Routine Catheter Abation | Ejection Fraction (EF) | Baseline | 63.84 percent of blood | Standard Deviation 6.25 |
| Routine Catheter Abation | Ejection Fraction (EF) | 12 months | 64.5 percent of blood | Standard Deviation 4.53 |
Secondary
Freedom From AF Recurrence Despite Taking AADs
Freedom from AF recurrence through 24 months (not-including the pre-defined 90 day blanking period) despite taking AADs
Time frame: up to 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Renal Sympathetic Denervation PLUS Catheter Ablation | Freedom From AF Recurrence Despite Taking AADs | 6 recurrences |
| Routine Catheter Abation | Freedom From AF Recurrence Despite Taking AADs | 5 recurrences |
Secondary
Left Atrial (LA) Size
LA size by TTE at baseline and at 12 months
Time frame: at baseline and at 12 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Renal Sympathetic Denervation PLUS Catheter Ablation | Left Atrial (LA) Size | Baseline | 5.4 cm | Standard Deviation 0.8 |
| Renal Sympathetic Denervation PLUS Catheter Ablation | Left Atrial (LA) Size | 12 months | 5.19 cm | Standard Deviation 0.9 |
| Routine Catheter Abation | Left Atrial (LA) Size | Baseline | 4.7 cm | Standard Deviation 1.3 |
| Routine Catheter Abation | Left Atrial (LA) Size | 12 months | 4.68 cm | Standard Deviation 1.4 |
Secondary
Number of Anti-hypertensive Medications
Total number of anti-hypertensive medications at study end, compared between the two treatment arms
Time frame: baseline and 24 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Renal Sympathetic Denervation PLUS Catheter Ablation | Number of Anti-hypertensive Medications | Baseline | 2.8 medications | Standard Deviation 0.95 |
| Renal Sympathetic Denervation PLUS Catheter Ablation | Number of Anti-hypertensive Medications | 24 months | 2.8 medications | Standard Deviation 1 |
| Routine Catheter Abation | Number of Anti-hypertensive Medications | Baseline | 2.5 medications | Standard Deviation 1 |
| Routine Catheter Abation | Number of Anti-hypertensive Medications | 24 months | 2.35 medications | Standard Deviation 1 |
Secondary
Number of Participants With Major Adverse Cardiac Events (MACE)
Number of Participants with Major adverse cardiac events (MACE) defined as a non-weighted composite score of: death, stroke, CHF hospitalization, and clinically diagnosed thromboembolic events other than stroke and hemorrhage requiring transfusion within 12 months of randomization
Time frame: within 12 months of randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Sympathetic Denervation PLUS Catheter Ablation | Number of Participants With Major Adverse Cardiac Events (MACE) | 0 Participants |
| Routine Catheter Abation | Number of Participants With Major Adverse Cardiac Events (MACE) | 1 Participants |
Secondary
Number of Participants With Procedure Adverse Events
Causality will be defined as adverse events that, after careful medical evaluation, are considered with a high degree of certainty to be related to the intervention (AF ablation ± renal sympathetic denervation).
Time frame: up to 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Sympathetic Denervation PLUS Catheter Ablation | Number of Participants With Procedure Adverse Events | 6 Participants |
| Routine Catheter Abation | Number of Participants With Procedure Adverse Events | 1 Participants |
Secondary
Number of Participants With Serious Adverse Events (SAE)
SAE-any experience that results in a fatality or is life threatening; results in significant or persistent disability; requires or prolongs hospitalization; results in congenital anomaly/birth defect; or represents other significant hazards or potentially serious harm to research subjects or others, in the opinion of the investigators. Important medical events that may not result in above may be considered a SAE when, based upon appropriate medical judgment, they may jeopardize the patient and may require medical or surgical intervention to prevent one of the outcomes listed in this definition
Time frame: up to 24 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Renal Sympathetic Denervation PLUS Catheter Ablation | Number of Participants With Serious Adverse Events (SAE) | 5 Participants |
| Routine Catheter Abation | Number of Participants With Serious Adverse Events (SAE) | 1 Participants |