Please select the eligibility criteria that correspond to the clinical trial below.
Title: The "RADIANCE-HTN" Study. A Study of the ReCor Medical Paradise System in Clinical Hypertension
Brief Summary: RADIANCE-HTN is a randomized, double-blind, sham controlled, 2-cohort study (TRIO and SOLO) designed to demonstrate efficacy and document the safety of the Paradise Renal Denervation System in two distinct populations of hypertensive subjects.


Options:
A: Inclusion Criteria:

* Individual is ≥ 18 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 2 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

Exclusion Criteria:

* 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.
B: 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* In the investigator's opinion the patient can not be withdrawn from their current antihypertensive medication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
C: Inclusion Criteria:

* Symptomatic drug-refractory AF (with history of failure of ≥2 class I or III antiarrhythmic drugs) in patients referred for catheter ablation of AF
* PAF with ≥1 monthly episodes or PersAF in patients who had already undergone ≥3 electrical cardioversions. PAF was defined as episodes lasting less than 7 days with spontaneous termination. PersAF was defined as lasting more than 7 days before being terminated pharmacologically or by electrical cardioversion.
* Office-based systolic blood pressure of ≥160 mm Hg, despite treatment with ≥3 antihypertensive drugs (including 1 diuretic)
* A glomerular filtration rate ≥45 mL/min/1⋅73 m2, with modification of diet using a renal disease formula

Exclusion Criteria:

* Previous atrial fibrillation ablation
* Type 1 of diabetes mellitus
* Structural heart disease
* Secondary cause of atrial hypertension
* Severe renal artery stenosis or renal arteries abnormalities
* Previous operations on renal arteries
* Pregnancy
* Previous heart, kidney, liver, or lung transplantation
* Unwillingness of participant
D: TRIO and SOLO Inclusion Criteria:

* Appropriately signed and dated informed consent
* Age ≥18 and ≤75 years at time of consent
* Documented history of essential hypertension
* SOLO Cohort only: Either an average seated office BP \< 180/110 mmHg at screening visit while on a stable regimen of 1 or 2 antihypertensive medications for at least 4 weeks prior to consent or an average seated office BP ≥ 140/90 mmHg \<180/110 mmHg despite lifestyle measures on no antihypertensive medications
* TRIO Cohort only: Average seated office BP ≥ 140/90 mmHg at screening visit while on a stable regimen of at least 3 antihypertensive medications of different classes including a diuretic for at least 4 weeks prior to consent
* Documented daytime ABP ≥ 135/85 mmHg and \< 170/105 mmHg after 4-week washout/run-in period (SOLO cohort) or after 4-week stabilization period (TRIO cohort)
* Suitable renal anatomy compatible with the renal denervation procedure and documented by renal CTA or MRA of good quality performed within one year prior to consent (a CTA or MRA will be obtained in patients without a recent (≤1 year) renal imaging)
* Able and willing to comply with all study procedures

Solo Exclusion Criteria:

* Renal artery anatomy on either side, ineligible for treatment including:

  * Main renal artery diameter \< 4 mm and \> 8 mm
  * Main renal artery length \< 25 mm
  * A single functioning kidney
  * Presence of abnormal kidney (or secreting adrenal) tumors
  * Renal artery with aneurysm
  * Pre-existing renal stent or history of renal artery angioplasty
  * Prior renal denervation procedure
  * Fibromuscular disease of the renal arteries
  * Presence of renal artery stenosis of any origin ≥ 30%
  * Accessory arteries with diameter ≥ 2mm \<4 mm and \> 8 mm\*
* Evidence of active infection within 7 days of procedure
* Iliac/femoral artery stenosis precluding insertion of the Paradise Catheter
* Type I diabetes mellitus or uncontrolled Type II diabetes (defined as a plasma Hb1Ac ≥ 9.0%)
* Documented history of chronic active inflammatory bowel disorders such as Chrohn's disease or ulcerative colitis
* eGFR of \<40 mL/min/1.73 m2 (by Modification of Diet in Renal Disease formula)
* Brachial circumference ≥ 42 cm
* Any history of cerebrovascular event (e.g. stroke, transient ischemic event, cerebrovascular accident)
* Any history of severe cardiovascular event (myocardial infarction, CABG, acute heart failure requiring hospitalization (NYHA III-IV)
* Documented confirmed episode(s) of stable or unstable angina
* Documented repeat (\>1) hospitalization for hypertensive crisis within the prior 12 months
* Prescribed to any standard antihypertensive of cardiovascular medication (e.g. beta blockers) for other chronic conditions (e.g. ischemic heart disease) such that discontinuation might pose serious risk to health
* Documented history of persistent or permanent atrial tachyarrhythmia
* Active implantable medical device (e.g. ICD or CRT-D; neuromodulator/spinal stimulator; baroreflex stimulator)
* Chronic oxygen support or mechanical ventilation other than nocturnal respiratory support for sleep apnea.
* Primary pulmonary hypertension
* Documented contraindication or allergy to contrast medium not amenable to treatment
* Limited life expectancy of \< 1 year at the discretion of the Investigator
* Any known, unresolved history of drug use or alcohol dependency, lacks the ability to comprehend or follow instructions, or for any reason in the opinion of the investigator, would be unlikely or unable to comply with study protocol requirements or whose participation may result in data analysis confounders (e.g. night shift workers)
* Pregnant, nursing or planning to become pregnant (negative pregnancy test required, documented within a maximum of 7 days prior to procedure for all women of child bearing potential. Documentation of effective contraception is also required for women of child bearing potential) Concurrent enrollment in any other investigational drug or device trial (participation in non-interventional Registries is acceptable)

TRIO Exclusion Criteria

* Renal artery anatomy on either side, ineligible for treatment including:

  * Main renal artery diameter \< 3.5 mm and \> 8 mm
  * Main renal artery length \< 20 mm
  * A single functioning kidney
  * Presence of abnormal kidney tumors
  * Renal artery with aneurysm
  * Pre-existing renal stent or history of renal artery angioplasty
  * Pre-existing aortic stent or history of aortic aneurysm
  * Prior renal denervation procedure
  * Fibromuscular disease of the renal arteries
  * Presence of renal artery stenosis of any origin ≥ 30%
  * Accessory arteries with diameter ≥2 mm \<3.5 mm and \> 8 mm\*
* Iliac/femoral artery stenosis precluding insertion of the Paradise Catheter
* Evidence of active infection within 7 days of procedure
* Secondary hypertension not including sleep apnea (documented through clinical work up within the 12 months prior to consent- see protocol body for details)
* Type I diabetes mellitus or uncontrolled Type II diabetes (defined as a plasma Hb1Ac ≥ 9.0%)
* Documented history of chronic active inflammatory bowel disorders such as Crohn's disease or ulcerative colitis
* eGFR of \<40 mL/min/1.73 m2 (by Modification of Diet in Renal Disease formula)
* Brachial circumference ≥ 42 cm
* Any history of cerebrovascular event (e.g. stroke, transient ischemic event, cerebrovascular accident) within 3 months prior to consent
* Any history of severe cardiovascular event (e.g. myocardial infarction, CABG, acute heart failure requiring hospitalization (NYHA III-IV) within 3 months prior to consent
* Documented repeat (\>1) hospitalization for hypertensive crisis within the prior 3 months
* Documented confirmed episode(s) of unstable angina within 3 months prior to consent
* Documented intolerance or contraindication for any of the antihypertensive drugs prescribed as a requirement of the study protocol
* Prescribed to any standard anti-hypertensive CV medication (other than beta blockers) for other chronic conditions (e.g. ischemic heart disease) such that discontinuation might pose serious risk to health
* Documented history of persistent or permanent atrial tachyarrhythmia
* Active implantable medical device (e.g. ICD or CRT-D; neuromodulator/spinal stimulator; baroreflex stimulator)
* Chronic oxygen support or mechanical ventilation other than nocturnal respiratory support for sleep apnea.
* Primary pulmonary hypertension
* Documented contraindication or allergy to contrast medium not amenable to treatment
* Limited life expectancy of \< 1 year at the discretion of the Investigator
* Night shift workers
* Any known, unresolved history of drug use or alcohol dependency, lacks the ability to comprehend or follow instructions, or for any reason in the opinion of the investigator, would be unlikely or unable to comply with study protocol requirements or whose participation may result in data analysis confounders
* Pregnant, nursing or planning to become pregnant (documented negative pregnancy test required documented within a maximum of 7 days prior to procedure for all women of child bearing potential. Documentation of effective contraception is also required for women of child bearing potential)
* Concurrent enrollment in any other investigational drug or device trial (participation in non-interventional Registries is acceptable)

Answer: D