Please select the eligibility criteria that correspond to the clinical trial below.
Title: Global Clinical Study of Renal Denervation With the Symplicity Spyral™ Multi-electrode Renal Denervation System in Patients With Uncontrolled Hypertension in the Absence of Antihypertensive Medications (SPYRAL PIVOTAL - SPYRAL HTN-OFF MED)
Brief Summary: The purpose of this study is to test the hypothesis that renal denervation decreases blood pressure and is safe when studied in the absence of antihypertensive medications.


Options:
A: Inclusion Criteria:

* Male or female aged 18 to 75 years (females of child bearing potential must be using adequate contraceptive precautions)
* Females of childbearing potential or within two years of the menopause must have a negative urine pregnancy test at enrolment visit
* Patients with mild to moderate uncomplicated essential hypertension with a trough mean sitting DBP ≥ 90 mmHg and/or SBP ≥ 140 mmHg or pretreated arterial hypertension
* Written informed consent
* Agreement to attend all study visits as planned in the protocol
* Agreement to perform routinely self home blood pressure measurements as well as keep a blood pressure diary throughout the study and to inform the investigator if BP exceeds cutt off criteria given in the ICF

Exclusion Criteria:

* In the investigator's opinion the patient can not be withdrawn from their current antihypertensive medication
* Secondary hypertension (e.g. patients with hyperaldosteronism, pheochromocytoma, renal artery stenosis, renal parenchymal disease, coarctation of the aorta, Cushing's disease syndrome)
* Severe essential hypertension (systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 110 mmHg) or treatment resistant hypertension (3 antihypertensive drugs and still SBP ≥ 140mmHg and/or DBP ≥ 90mmHg)
* History of hypertensive encephalopathy or intracerebral hemorrhage
* Diabetes mellitus Type 1 or Type 2
* History of epilepsia (no retinal exam possible)
* Eye cataract (no retinal exam possible)
* History of the following within the last six months: myocardial infarction, unstable angina pectoris, percutaneous coronary intervention, heart failure
* Presence of significant renal, respiratory, hepatic, gastrointestinal, endocrine or metabolic, immunological, haematological or oncological, neurological and psychiatric diseases or dysfunction
* Impaired renal function as shown by estimated GFR (abbreviated MDRD formula) \< 45 ml/min/1.73 m2
* Impaired hepatic function as shown by transaminases higher than three times the upper normal limit
* Known allergy or a known intolerance to any ARB or Aliskiren
* Females who are pregnant or lactating or who are not on an adequate contraception (Pearl-Index ≥ 1 %)
* Use of any investigational drug within 28 days before study entry
* Patients previously enrolled into the study
* History of drug, medication abuse.
* Serious disorders which may limit the ability to evaluate the efficacy or safety of the test drug(s), including cerebrovascular, cardiovascular, renal, respiratory, hepatic, gastrointestinal, endocrine or metabolic, immunological, haematological or oncological, neurological and psychiatric diseases
* Subject is the investigator or any subinvestigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the protocol
* Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
* Subject unlikely to comply with protocol, e.g. uncooperative attitude, inability to return for follow-up visits and unlikelihood of completing the study
* Subject who do not give written consent, that pseudonymous data will be transferred in line with the duty of documentation and the duty of notification according to § 12 and § 13 GCP-V
B: Inclusion Criteria:

* Individual is ≥ 20 and ≤ 80 years old at time of randomization.
* Individual is receiving a stable medication regimen including full tolerated doses of 3 or more anti-hypertensive medications of different classes, of which one must be a diuretic (with no changes for a minimum of 6 weeks prior to screening) that is expected to be maintained without changes for at least 6 months.
* Individual has an office systolic blood pressure (SBP) of ≥ 160 mmHg based on an average of 3 blood pressure readings measured at both an initial screening visit and a confirmatory screening visit
* 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 highlights:

* Individual has an estimated glomerular filtration rate (eGFR) of \< 45 mL/min/1.73 m2
* Individual has an Ambulatory Blood Pressure Monitoring (ABPM) 24 hour average SBP \< 135 mmHg
* Individual has type 1 diabetes mellitus
* Individual requires chronic oxygen support or mechanical ventilation (e.g., tracheostomy, CPAP, BiPAP) other than nocturnal respiratory support for sleep apnea.
* Individual has primary pulmonary hypertension.
* Individual is pregnant, nursing or planning to be pregnant.
C: Inclusion Criteria:

* Individual has office systolic blood pressure (SBP) ≥ 150 mmHg and \<180 mmHg and a diastolic blood pressure (DBP) ≥ 90 mmHg after being off medications.
* Individual has 24-hour Ambulatory Blood Pressure Monitoring (ABPM) average SBP ≥ 140 mmHg and \< 170 mmHg.
* Individual is willing to discontinue current antihypertensive medications.

Exclusion Criteria:

* Individual lacks appropriate renal artery anatomy.
* Individual has estimated glomerular filtration rate (eGFR) of \<45.
* Individual has type 1 diabetes mellitus or poorly-controlled type 2 diabetes mellitus.
* Individual has one or more episodes of orthostatic hypotension.
* Individual requires chronic oxygen support or mechanical ventilation other than nocturnal respiratory support for sleep apnea.
* Individual has primary pulmonary hypertension.
* Individual is pregnant, nursing or planning to become pregnant.
* Individual has frequent intermittent or chronic pain that results in treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) for two or more days per week over the month prior to enrollment.
* Individual has stable or unstable angina within 3 months of enrollment, myocardial infarction within 3 months of enrollment; heart failure, cerebrovascular accident or transient ischemic attack, or atrial fibrillation at any time.
* Individual works night shifts.
D: Inclusion Criteria:

* Systolic daytime ambulatory BP at least 145 mmHg and compliance to a minimum of 3 antihypertensive drugs, including a diuretic, or in case of diuretic intolerance at least 3 nondiuretic antihypertensive drugs.

Exclusion Criteria:

* Pregnancy
* Non compliance
* Heart Failure (NYHA 3-4)
* LV ejection fraction \< 50 %
* Renal insufficiency (eGFR\<30)
* Unstable coronary heart disease
* Coronary intervention within 6 months
* Myocardial infarction within 6 months
* Claudication
* Orthostatic syncope within 6 months
* Secondary Hypertension
* Permanent atrial fibrillation
* Significant Heart Valve Disease
* Clinically Significant abnormal electrolytes, haemoglobin, Liver enzymes, TSH
* Second and third degree heart block
* Macroscopic haematuria
* Proximal significant coronary stenosis
* Renal artery anatomy not suitable for renal artery ablation (Stenosis, small diameter \< 4 mm, length \< 2 cm, multiple renal arteries, severe calcifications)

Answer: C