Global Clinical Study of Renal Denervation with the Symplicity Spyral* multi-electrode renal denervation system in Patients with Uncontrolled Hypertension on Standard Medical Therapy

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 24

Inclusion Criteria

1. Individual is * 20 and * 80 years old at time of randomization.
2. Individual has an office systolic blood pressure (SBP) * 150 mm Hg and < 180 mm Hg and an office diastolic blood pressure (DBP) * 90 mm Hg (according to guidelines in Appendix L.7 of the protocol) at Screening Visit 1 and Screening Visit 2 when receiving a medication regimen of three antihypertensive medications on at least 50% of the maximum manufacturer*s dosage; the three anti-hypertensive medications must include a thiazide-type diuretic, a dihydropyridine calcium channel blocker, and an ACE-I/ARB and the subject must be on a stable dose of each medication for at least six weeks prior to Screening Visit 1 and up to Screening Visit 2. Note: In Japan, patients may be prescribed less than 50% of maximum manufacturer*s recommended dosage of a thiazide-type diuretic per standard of care.
3. Individual has a 24-hour ABPM average of SBP * 140 and < 170 mm Hg measured at Screening Visit 2 according to guidelines in Appendix L.7 of the protocol after witnessed antihypertensive drug ingestion prior to applying the ABPM device.
4. Individual agrees to have all study procedures performed, and is competent and willing to provide written, informed consent to participate in this clinical study.

Exclusion Criteria

1. Individual has undergone prior renal denervation.
2. Individual has renal artery anatomy that is ineligible for treatment including:
a. Lacks at least one renal arterial vessel for each kidney greater than 3 mm and less than 8 mm in diameter (including accessory, branch, and main renal arteries)
b. Main renal artery which contains renal artery stenosis (> 50%), renal artery aneurysm, fibromuscular dysplasia (FMD), presence of a renal artery stent or calcification which does not allow at least four radio frequency ablations to be delivered in areas free of these abnormalities. FMD is defined as visible beading of the artery on angiography.
c. Unilateral kidney.
3. Individual has an estimated glomerular filtration rate (eGFR) of < 45 mL/min/1.73m2, using the MDRD calculation. (Note: an eGFR calculation specific to Japanese patients will be used for subjects enrolled in Japan)
4. Individual has documented type 1 diabetes mellitus or poorly-controlled type 2 diabetes mellitus with glycosylated hemoglobin greater than 8.0%.
5. Individual has had * 1 episode(s) of orthostatic hypotension not related to medication changes within the past year or has a reduction of SBP of * 20 mm Hg or DBP of *10 mm Hg within 3 minutes of standing coupled with symptoms during the screening process.
6. Individual requires chronic oxygen support or mechanical ventilation other than nocturnal respiratory support for sleep apnea (e.g. CPAP, BiPAP).
7. Individual is being treated chronically (e.g. daily use) with non-steroidal anti-inflammatory drugs (NSAIDs). Aspirin therapy is allowed.
8. Individual has documented primary pulmonary hypertension.
9. Individual has known pheochromocytoma, Cushing*s Disease (adrenal insufficiency), primary hyperaldosteronism, coarctation of the aorta, untreated hyperthyroidism, untreated hypothyroidism, or primary hyperparathyroidism. (Note: treated hyperthyroidism and treated hypothyroidism are permissible).
10. Individual has experienced a myocardial infarction, unstable angina pectoris, syncope, or a cerebrovascular accident within three months of the screening period, or has widespread atherosclerosis, with documented intravascular thrombosis or unstable plaques.
11. Individual has a scheduled or planned surgery that, in the opinion of the Investigator, may affect study endpoints.
12. Individual has a documented condition that would prohibit or interfere with ability to obtain an accurate blood pressure measurement using the protocol-specified automatic blood pressure monitor (e.g., upper arm circumference outside cuff size ranges available by geography or arrhythmia that interferes with automatic monitor*s pulse sensing and prohibits an accurate measurement).
13. Individual works night shifts.
14. Individual has severe cardiac valve stenosis for which, in the opinion of the investigator, a significant reduction of blood pressure is contraindicated.
15. Individual has a documented confounding medical condition, which in the opinion of the investigator, may adversely affect the safety of the participant (e.g. patients with clinically significant peripheral vascular disease, aortic aneurysm, bleeding disorders such as thrombocytopenia, hemophilia, or significant anemia).
16. Individual is pregnant, nursing or planning to become pregnant during the course of the study follow-up. (Note: Pre-menopausal female participants must have a negative serum or urine