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

Phase 2

Withdrawn

Conditions: drug resistant high blood pressure
resistant Hypertension
10057166

Registration Number: NL-OMON46497

Lead Sponsor: Vascular Dynamics

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 33

Inclusion Criteria

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.

Exclusion Criteria

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-morbi

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p> The primary efficacy endpoint is the difference in the change in mean systolic<br /><br>24-hour ambulatory blood pressure from baseline to 180 days post-randomization,<br /><br>between the treatment arm and the sham arm. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Exploratory efficacy endpoints are differences in a) in mean day-time and<br /><br>night-time 24-hr ambulatory systolic blood (24hr sABP) from baseline to the<br /><br>365-day visit. b) in number and dosage of antihypertensive medications from<br /><br>baseline to 90, 180 and 365 days; c) in quality of life scores; d) in<br /><br>healthcare utilization including number of hospitalizations and office visits<br /><br>due to hypertension; between the treatment and sham arms.<br /><br>Safety will be evaluated by assessing the following:<br /><br>• Adverse events (AEs)<br /><br>• Serious adverse events (SAEs)<br /><br>• Composite measure of death, MI, stroke, device embolization, carotid<br /><br>occlusion, new ipsilateral carotid stenosis requiring surgical or percutaneous<br /><br>intervention, or Bleeding Academic Research Consortium (BARC) 3 to 5 bleeding<br /><br>at the 90-day visit window.</p><br>