Hypertension, Renal
Conditions
Keywords
Renal Sympathetic Denervation
Brief summary
This is a prospective, multi-center, non-randomized, feasibility study to assess the safety and effectiveness of renal artery sympathetic denervation using the investigational devices in subjects with resistant hypertension.
Interventions
DEVICECelsius® ThermoCool® Renal Denervation
The investigational device is indicated for the treatment of resistant hypertension by renal denervation.
Sponsors
Biosense Webster, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
1. Subject has a systolic blood pressure ≥ 140 mmHg based on an average of 3 office blood pressure readings measured according to the BP guidelines. 2. Subject is adhering to a stable drug regimen of at least 3 different classes of anti-hypertensive medications, including a diuretic (with no changes for a minimum of 2 weeks prior to enrollment) at optimal dose and is expected to be maintained for at least 6 months. 3. Subject is \> 18 and \< 85 years of age. 4. Subject agrees to have all study procedures performed, and is competent and willing to provide written, informed consent to participate in this study. Key
Exclusion criteria
1. A secondary cause of hypertension, e.g. white coat hypertension (assessed by 24 h ABPM at physician's discretion), primary aldosteronism, pheochromocytoma, renal artery stenosis, drug induced-hypertension, Adult Polycystic kidney Disease, renal cell carcinoma, pyelonephritis, glomerulonephritis, coarctation of the aorta, acromegaly, Cushing's Syndrome, Conn's (primary hyperaldosteronism), polyarteritis nodosum, systemic sclerosis, parenchymal kidney disease, obstructive sleep apnoea based on a workup performed within the 12 months preceding enrollment. 2. Subject has aorto-ilio-femoral artery anatomy not suitable for treatment with the investigational device(s). 3. Subject has main renal arteries that are \< 20 mm in length or \< 4 mm in diameter. 4. Subject has a prior history of any renal artery intervention including but not limited to balloon angioplasty, stenting, renal denervation or surgery. 5. Subject has an estimated glomerular filtration rate (eGFR) of \< 45mL/min/1.73m2, using the MDRD formula. 6. Subject has type 1 diabetes mellitus. 7. Subject has history of Myocardial Infarction, unstable angina pectoris, or a cerebrovascular accident in the 6 months period prior to enrolment, or documented widespread atherosclerosis, intravascular thrombosis or unstable plaques. 8. Subject has hemodynamically significant valvular heart disease for which reduction of blood pressure would be considered hazardous.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Major Adverse Events That Occurred Within 30 Days Post-procedure. | 30 days post-procedure | Major adverse events include Acute myocardial infarction; Death from progressive heart failure, death from aortic or peripheral artery disease, from renal failure and sudden cardiac death; New-onset heart failure; Stroke; Aortic or lower limb revascularization procedure; Lower limb amputation; Beginning dialysis; Hospital admission for hypertensive emergency unrelated to non-adherence or non-persistence with drugs at each follow up visit; Hospitalization for atrial fibrillation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Adverse Cardiovascular and Renal Events Within the 12 Month Follow-up Visit | 12 months post-procedure | These adverse events include renal artery stenosis (≥60% diameter reduction confirmed by MRI or renal angiography); peri-procedural renal artery dissection or perforation requiring intervention, serious arterial access site related complications requiring intervention or prolonging hospitalization; ≥25% reduction between baseline and 12 months in renal function measured by the estimated Glomerular Filtration Rate (eGFR), as well as composite of major adverse cardiovascular and/or renal events. |
| Mean Change in Office Systolic Blood Pressure and Diastolic Blood Pressure From Baseline to 1 ,3, 6 and 12 Months Post Procedure | 12 months post-procedure | Office systolic blood pressure (SBP) and diastolic blood pressure (DBP) measures were summarized to assess the reduction in blood pressure from baseline visit to post baseline at 1, 3, 6, and 12 months. Negative values for change represent reductions. |
| Incidence of Subjects Achieving Target Systolic Blood Pressure (SBP) at 1, 3, 6 and 12 Months Post Procedure | 12 months post-procedure | The pre-specified target SBP is defined as SBP \<130 mmHg. This endpoint is defined at each of 1, 3, 6 and 12 months post procedure. |
| Incidence of Subjects Achieving a ≥ 10 mmHg Reduction in Systolic Blood Pressure (SBP) at 1, 3, 6 and 12 Months Post Procedure | 12 months post-procedure | Incidence of subjects achieving a 10 mmHg or more reduction in Systolic Blood Pressure (SBP) at 1, 3, 6 and 12 months post procedure. |
Participant flow
Recruitment details
The study enrollment took approximately 3 months, began on October 21, 2013 and completed on December 17, 2013. A total of 37 subjects were consented and 19 underwent treatment with the study catheter in 4 investigation sites in New Zealand, Czech Republic, and Italy.
Participants by arm
| Arm | Count |
|---|---|
| Renal Artery Sympathetic Denervation Subjects enrolled in this study underwent the renal artery sympathetic denervation procedure for treating moderate resistant hypertension. The procedure was conducted with the investigational Celsius® ThermoCool® Renal Denervation catheter. | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | Renal Artery Sympathetic Denervation |
|---|---|
| Age, Continuous | 57.5 years STANDARD_DEVIATION 10.4 |
| Race/Ethnicity, Customized African Descent | 1 participants |
| Race/Ethnicity, Customized Not African Descent | 18 participants |
| Region of Enrollment Czech Republic | 9 participants |
| Region of Enrollment Italy | 4 participants |
| Region of Enrollment New Zealand | 6 participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 8 / 19 |
| serious Total, serious adverse events | 0 / 19 |
Outcome results
Primary
Incidence of Major Adverse Events That Occurred Within 30 Days Post-procedure.
Major adverse events include Acute myocardial infarction; Death from progressive heart failure, death from aortic or peripheral artery disease, from renal failure and sudden cardiac death; New-onset heart failure; Stroke; Aortic or lower limb revascularization procedure; Lower limb amputation; Beginning dialysis; Hospital admission for hypertensive emergency unrelated to non-adherence or non-persistence with drugs at each follow up visit; Hospitalization for atrial fibrillation.
Time frame: 30 days post-procedure
Population: The Safety Analysis population which consists of all enrolled subjects who have undergone insertion of the study ablation catheter.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Renal Artery Sympathetic Denervation | Incidence of Major Adverse Events That Occurred Within 30 Days Post-procedure. | 0.0 percentage of participants |
Secondary
Incidence of Adverse Cardiovascular and Renal Events Within the 12 Month Follow-up Visit
These adverse events include renal artery stenosis (≥60% diameter reduction confirmed by MRI or renal angiography); peri-procedural renal artery dissection or perforation requiring intervention, serious arterial access site related complications requiring intervention or prolonging hospitalization; ≥25% reduction between baseline and 12 months in renal function measured by the estimated Glomerular Filtration Rate (eGFR), as well as composite of major adverse cardiovascular and/or renal events.
Time frame: 12 months post-procedure
Population: The safety analysis population consists of all enrolled subjects who have undergone insertion of the study ablation catheter.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Renal Artery Sympathetic Denervation | Incidence of Adverse Cardiovascular and Renal Events Within the 12 Month Follow-up Visit | 42.1 percentage of participants |
Secondary
Incidence of Subjects Achieving a ≥ 10 mmHg Reduction in Systolic Blood Pressure (SBP) at 1, 3, 6 and 12 Months Post Procedure
Incidence of subjects achieving a 10 mmHg or more reduction in Systolic Blood Pressure (SBP) at 1, 3, 6 and 12 months post procedure.
Time frame: 12 months post-procedure
Population: Effectiveness analysis population, which consists of enrolled subjects without enrollment deviation and experiencing technical success. Technical success is defined as the investigational catheter being successfully inserted into the femoral artery with radiofrequency energy successfully applied in at least one artery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Renal Artery Sympathetic Denervation | Incidence of Subjects Achieving a ≥ 10 mmHg Reduction in Systolic Blood Pressure (SBP) at 1, 3, 6 and 12 Months Post Procedure | 71.4 percentage of participants |
| Change in Blood Pressure at 3 Months Follow Up | Incidence of Subjects Achieving a ≥ 10 mmHg Reduction in Systolic Blood Pressure (SBP) at 1, 3, 6 and 12 Months Post Procedure | 50 percentage of participants |
| Change in Blood Pressure at 6 Months Follow Up | Incidence of Subjects Achieving a ≥ 10 mmHg Reduction in Systolic Blood Pressure (SBP) at 1, 3, 6 and 12 Months Post Procedure | 50 percentage of participants |
| Change in Blood Pressure at 12 Month Follow Up | Incidence of Subjects Achieving a ≥ 10 mmHg Reduction in Systolic Blood Pressure (SBP) at 1, 3, 6 and 12 Months Post Procedure | 53.8 percentage of participants |
Secondary
Incidence of Subjects Achieving Target Systolic Blood Pressure (SBP) at 1, 3, 6 and 12 Months Post Procedure
The pre-specified target SBP is defined as SBP \<130 mmHg. This endpoint is defined at each of 1, 3, 6 and 12 months post procedure.
Time frame: 12 months post-procedure
Population: Effectiveness analysis population, which consists of enrolled subjects without enrollment deviation and experiencing technical success. Technical success is defined as the investigational catheter being successfully inserted into the femoral artery with radiofrequency energy successfully applied in at least one artery.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Renal Artery Sympathetic Denervation | Incidence of Subjects Achieving Target Systolic Blood Pressure (SBP) at 1, 3, 6 and 12 Months Post Procedure | 28.6 percentage of participants |
| Change in Blood Pressure at 3 Months Follow Up | Incidence of Subjects Achieving Target Systolic Blood Pressure (SBP) at 1, 3, 6 and 12 Months Post Procedure | 7.1 percentage of participants |
| Change in Blood Pressure at 6 Months Follow Up | Incidence of Subjects Achieving Target Systolic Blood Pressure (SBP) at 1, 3, 6 and 12 Months Post Procedure | 7.1 percentage of participants |
| Change in Blood Pressure at 12 Month Follow Up | Incidence of Subjects Achieving Target Systolic Blood Pressure (SBP) at 1, 3, 6 and 12 Months Post Procedure | 7.1 percentage of participants |
Secondary
Mean Change in Office Systolic Blood Pressure and Diastolic Blood Pressure From Baseline to 1 ,3, 6 and 12 Months Post Procedure
Office systolic blood pressure (SBP) and diastolic blood pressure (DBP) measures were summarized to assess the reduction in blood pressure from baseline visit to post baseline at 1, 3, 6, and 12 months. Negative values for change represent reductions.
Time frame: 12 months post-procedure
Population: Effectiveness analysis population, which consists of enrolled subjects without enrollment deviation and experiencing technical success. Technical success is defined as the investigational catheter being successfully inserted into the femoral artery with radiofrequency energy successfully applied in at least one artery.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Renal Artery Sympathetic Denervation | Mean Change in Office Systolic Blood Pressure and Diastolic Blood Pressure From Baseline to 1 ,3, 6 and 12 Months Post Procedure | Mean Reduction in SBP | -16.4 mmHg | Standard Deviation 18.3 |
| Renal Artery Sympathetic Denervation | Mean Change in Office Systolic Blood Pressure and Diastolic Blood Pressure From Baseline to 1 ,3, 6 and 12 Months Post Procedure | Mean Reduction in DBP | -10.1 mmHg | Standard Deviation 12.1 |
| Change in Blood Pressure at 3 Months Follow Up | Mean Change in Office Systolic Blood Pressure and Diastolic Blood Pressure From Baseline to 1 ,3, 6 and 12 Months Post Procedure | Mean Reduction in DBP | -5.2 mmHg | Standard Deviation 11.7 |
| Change in Blood Pressure at 3 Months Follow Up | Mean Change in Office Systolic Blood Pressure and Diastolic Blood Pressure From Baseline to 1 ,3, 6 and 12 Months Post Procedure | Mean Reduction in SBP | -14.5 mmHg | Standard Deviation 25.1 |
| Change in Blood Pressure at 6 Months Follow Up | Mean Change in Office Systolic Blood Pressure and Diastolic Blood Pressure From Baseline to 1 ,3, 6 and 12 Months Post Procedure | Mean Reduction in DBP | -1.3 mmHg | Standard Deviation 10.2 |
| Change in Blood Pressure at 6 Months Follow Up | Mean Change in Office Systolic Blood Pressure and Diastolic Blood Pressure From Baseline to 1 ,3, 6 and 12 Months Post Procedure | Mean Reduction in SBP | -11.3 mmHg | Standard Deviation 24.4 |
| Change in Blood Pressure at 12 Month Follow Up | Mean Change in Office Systolic Blood Pressure and Diastolic Blood Pressure From Baseline to 1 ,3, 6 and 12 Months Post Procedure | Mean Reduction in DBP | -4.9 mmHg | Standard Deviation 10.3 |
| Change in Blood Pressure at 12 Month Follow Up | Mean Change in Office Systolic Blood Pressure and Diastolic Blood Pressure From Baseline to 1 ,3, 6 and 12 Months Post Procedure | Mean Reduction in SBP | -13.8 mmHg | Standard Deviation 23.9 |