CALM-2 - Controlling and Lowering Blood Pressure with the MobiusHD*

1. Age 18 to 80
2. Mean Direct Observed Therapy (DOT) 24 hour ambulatory systolic blood pressure >=145 mmHg and <=200 mmHg and stable for at least 8 weeks on a maximally tolerated guideline directed Guideline directed *A+C+D* antihypertensive medication regimen, where *A* is an angiotensin-converting enzyme Inhibitor or an angiotensin receptor blocker, *C* is a calcium channel blocker, and *D* is a diuretic. Patients that have documented intolerance to one or more of these drugs and are on an alternative 3-5 drug regimen will be reviewed and approved by the Hypertension Committee prior to inclusion in the trial.
3. Antihypertensive medication compliance based on DOT-ABPM and HPLC/GCMS analysis of a urine sample
4. Two consecutive DOT 24-hour systolic DOT-ABPM measurements within 20% of each other
5. Adequacy of the carotid anatomy for treatment with the MobiusHD implant based on carotid angiography.

1. Known or clinically suspected baroreflex failure or autonomic neuropathy
2. History of hypertensive crisis in the past 6 months
3. Known significant aortoiliac or common femoral artery disease that will prohibit safe femoral access;
4. Hypertension secondary to an identifiable cause other than treated sleep apnea
(e.g., hyperaldosteronism, renal artery stenosis, pheochromocytoma, Cushing's syndrome, coarctation of the aorta, hyper- or hypothyroidism and intracranial tumor)
5. Currently taking centrally acting agonists such as clonidine, moxonidine, or methyl dopa;
6. Treatable cause of hypertension including, but not limited to, improper BP measurement, volume overload and pseudotolerance (excessive sodium intake, volume retention from kidney disease, inadequate diuretic therapy), drug-induced or other causes (non-adherence, inadequate doses, inappropriate combinations, NSAIDs, COX-2 inhibitors, cocaine, amphetamines, or other drugs, sympathomimetics, oral contraceptives (confirmed cause of hypertension), adrenocortical steroids, cyclosporine, tacrolimus, erythropoietin, excessive licorice (including some chewing tobacco), ephedra, ma haung, bitter orange; and excessive alcohol intake
7. Upper arm circumference >46 cm and/or BMI >=45 kg/m2
8. Chronic atrial fibrillation, or intermittent atrial fibrillation with one or more episode(s) within the last twelve (12) months
9. History of major bleeding complications associated with dual anti-platelet therapy
10. History of known uncorrected or uncorrectable bleeding diathesis
11. History of Heparin Induced Thrombocytopenia (HIT)
12. Current or planned use of chronic anticoagulation therapy including vitamin K antagonists and novel oral anticoagulants (apixaban, rivaroxaban, dabigatran and edoxaban)
13. Active gastritis or peptic ulcer disease with documented active ulcer or gastrointestinal bleeding within the last 3 months
14. History of allergy to nickel, or allergy to contrast media or study medications that cannot be managed medically
15. Persistent symptomatic orthostatic hypotension (>20/10 mmHg after 5 minutes of standing upright)
16. Syncope documented to be related to changes in blood pressure within the last six (6) months
17. History of myocardial infarction or unstable angina within the past six (6) months
18. History of cerebral vascular accident (stroke or TIA) within the past year or NIHSS >=5 or mRS >1 or any prior stroke with permanent neurologic defect or any prior intracranial bleed
19. Prior carotid surgery or stent placement, therapeutic radiation to the neck, or endovascular stent placement in either carotid region
20. Severe valvular or structural heart disease (excluding left ventricular hypertrophy)
21. Severe chronic obstructive pulmonary disease (requiring twenty-four-hour oxygen or chronic oral steroids), severe asthma, or severe pulmonary hypertension (Pulmonary Artery Systoic Pressure PASP>70 mmHg or Pulmonary Vascular Resistance PVR >4.0 Woods Units, not correctable with IV diuretics or vasodilator therapy)
22. NYHA class III or IV heart failure or known reduced left ventricular function
(EF <30%)
23. Uncontrolled diabetes mellitus with HbA1c >=10 %
24. Clinical suspicion or history of vasculitis or other condition causing vasculitis (e.g. autoimmune disorders)
25. Active infection within the last month requiring antibiotics
26. Uncontrolled co-morbid medical condition, including mental health issues, that would adversely affect participation in the trial (including adherence with all follow-up procedures)
27. Co-morbid condition that reduces life expectancy to less than one (1) year
28. Planned surgery or other procedure within the next six (6) months requiring cessation of antiplatelet medications
29. Pregnant or lactating females. For females of child-bearing potential, a positive mandatory pregnancy test during screening or refusal to use a medically accepted method of birth control for the duration of the trial
30. Carotid duplex studies demonstrating obstructive carotid disease, plaque, ulceration or >150 micron intima-media thickness (IMT) at the site of implantation and/or proximal to the carotid artery bulb and >=50% disease distal to the carotid artery bulb, including the intracranial circulation
31. Chronic kidney disease (eGFR calculated by the Modification of Diet in Renal Disease equation <45 ml/min)
32. Any significant obstructive vascular disease, calcification or plaque of aortic arch and great vessels by MRA
33. Renal artery stenosis >50% or systolic gradient >10mmHg in borderline cases diagnosed by renal artery imaging in the last 12 months performed with acceptable renal artery imaging modalities including renal duplex, magnetic resonance angiography, CT angiography, and selective or nonselective renal angiography depending on trial site diagnostic standards
34. Internal carotid artery (ICA) lumen diameters <4.5 mm or >12.5 mm within the planned location of the implant placement via MRA or evidence of landing zone restrictions, such as inadequate length, vessel tapering, and/or vessel curvature that would preclude safe placement of the implant
35. Enrolled in a concurrent clinical trial of an investigational drug or device that has not yet reached its primary endpoint or may otherwise interfere in study processes or endpoints
36. Unable or unwilling to fulfill the protocol follow-up requirements
37. Evidence of any carotid plaque, ulceration or any stenosis on selective carotid angiography performed. Luminal diameters will be assessed to exclude subjects with ICA lumen diameters <5 mm or >11.75 mm within the planned location of the implant. Evidence of landing zone restrictions, such as inadequate length, vessel tapering, and/or vessel curvature that would preclude safe placement of the implant;
38. Any angiographic evidence of plaque or ulceration in the aortic arch and/or the supra aortic vasculature;
39. Inappropriate anatomy of the carotid bifurcation for deployment of the MobiusHD, including, but not limited to, tortuosity of the extracranial vessels and significant angulation of the common carotid artery bifurcation;
40. Type III arch or anatomy that creates for difficult ICA access and any significant calcification of the carotid bulb.
41. If renal angiography is performed due to inadequate renal screening imaging, a renal artery with stenosis of >50% or systolic gradient >10mmHg.
Day of Procedure
1. Evidence of any carotid plaque, ulceration or any stenosis on selective carotid angiography performed. Luminal diameters will be assessed to exclude subjects with ICA lumen diameters <5 mm or >11.75 mm within the planned location of the implant. Evidence of landing zone restrictions, such as inadequate length, vessel tapering, and/or vessel curvature that would preclude safe placement of the implant;
2. Any angiographic evidence of plaque or ulceration in the aortic arch and/or the supra aortic vasculature;
3. Inappropriate anatomy of the carotid bifurcation for deployment of the MobiusHD, including, but not limited to, tortuosity of the extracranial vessels and significant angulation of the common carotid artery bifurcation;
4. Type III arch or anatomy that creates for difficult ICA access and any significant calcification of the carotid bulb.
5. If renal angiography is performed due to inadequate renal screening imaging, a renal artery with stenosis of >50% or systolic gradient >10mmHg.