CALM-FIM_US -Controlling and Lowering Blood Pressure With the MobiusHD™ - A Prospective Multicenter Safety Study
Phase: NA
Conditions: Hypertension
Sponsor: Vascular Dynamics, Inc.

 
 
 
 
 
IDE PROTOCOL 
IDE# G130013 
 
CALM-FIM_US –CONTROLLING AND LOWERING BLOOD 
PRESSURE WITH THE MOBIUSHD™ 
A PROSPECTIVE MULTICENTER SAFETY STUDY 
 
 
 
 
 
 
STUDY SPONSOR: 
VASCULAR DYNAMICS, INC. 
2134 OLD MIDDLEFIELD WAY 
SUITE J 
MOUNTAIN VIEW, CA 94043 
 
 
 
 
 
VERSION 1 – JANUARY 2013 
VERSION 2 – MARCH 2013 
VERSION 3 – SEPTEMBER 2013 
VERSION 4 – DECEMBER 2013 
VERSION 5 – OCTOBER 2014 
 
 
 
 
 
 
 
 
Confidential 
This document contains Vascular Dynamics, Inc. proprietary information and shall not be duplicated, disclosed to others, 
or used for purposes other than to carry out the intent for which this material is delivered unless written consent is first 
obtained from Vascular Dynamics, Inc. 

INVESTIGATOR SIGNATURE PAGE 
  
PROTOCOL TITLE: 
 
CALM-FIM_US –CONTROLLING AND 
LOWERING BLOOD PRESSURE WITH THE 
MOBIUSHD™ - A PROSPECTIVE 
MULTICENTER SAFETY STUDY 
 
PROTOCOL NUMBER: 
 
CRD0152 
DATE: 
 
08 OCTOBER 2014 
STUDY SPONSOR: 
 
VASCULAR DYNAMICS, INC. 
2134 OLD MIDDLEFIELD WAY 
SUITE J 
MOUNTAIN VIEW, CALIFORNIA   94043 
(650) 963-9370 
 
 
  
DECLARATION OF INVESTIGATOR 
 
I have read the above Protocol and agree to adhere to the requirements.  I will provide copies of this 
Protocol and all pertinent information to the study personnel.  I will discuss this material with them 
and ensure they are fully informed regarding the investigational device and the conduct of the 
study. I will work according to the principles of Good Clinical Practice (GCP) according to 21 CFR 
Parts 50, 54, 56, and 812, to other applicable regulations, to applicable laws and to hospital 
Institutional Review Board / Ethics Committee (IRB/EC) requirements. 
 
 
Investigator Signature 
I have read and understand the contents of the Protocol.  I agree to follow and abide by the 
guidelines set forth in this document. 
 
 
 
Principal Investigator Signature: ________________________________ Date: _______________ 
 
 
 
 
 
 
 
 
            DD/MM/YY 
Principal Investigator Printed Name:_____________________________ 
 
Investigational Site: __________________________________________ 
 
 
 

 
STUDY PERSONNEL 
 
 
SPONSOR: 
Vascular Dynamics, Inc. 
2134 Old Middlefield Way  
Suite J 
Mountain View, CA 94043 
USA 
 
 
CLINICAL TRIAL 
MANAGEMENT: 
Vascular Dynamics, Inc. 
2134 Old Middlefield Way  
Suite J 
Mountain View, CA 94043 
USA 
 
 
INDEPENDENT DATA 
SAFETY MONITORING 
BOARD: 
Chairman –  
Gary M. Ansel, MD, FACC 
MidOhio Cardiology and Vascular Consultants 
 
 
ELECTRONIC DATABASE: 
MedNet Solutions, Inc. 
110 Cheshire Lane, Suite 300 
Minnetonka, MN 55305 USA 
Toll-free: (866) 258-2735 
 
  
 

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TABLE OF CONTENTS 
1.0 
PROTOCOL SYNOPSIS ................................................................................... 11 
2.0 
BACKGROUND AND INTRODUCTION....................................................... 17 
2.1  
CURRENT HYPERTENSION TREATMENT .................................................. 18 
2.1.1   Lifestyle Modification ........................................................................... 18 
2.1.2    Medical Treatment for Stage 1 and Stage 2 Hypertension ............... 19 
2.1.3   Baroreceptor Modulation for Hypertension ...................................... 21 
3.0 
MOBIUSHD™ SYSTEM ................................................................................... 23 
3.1  
DETAILED DESCRIPTION OF MOBIUSHD ................................................ 23 
3.2 
COMPONENTS ........................................................................................... 23 
3.2.1   MobiusHD (implant) ............................................................................... 24 
3.2.2   Delivery Catheter .................................................................................... 26 
3.3   
PRINCIPLE OF OPERATION ....................................................................... 28 
4.0 
STUDY OBJECTIVES ....................................................................................... 28 
5.0 
CLINICAL STUDY DESIGN ............................................................................ 28 
6.0 
STUDY POPULATION ..................................................................................... 33 
6.1 
INCLUSION CRITERIA ............................................................................... 33 
6.2 
EXCLUSION CRITERIA .............................................................................. 34 
7.0 
SUBJECT ENROLLMENT ............................................................................... 37 
8.0 
STUDY METHODS............................................................................................ 38 
8.1 
MEDICAL THERAPY REGIMEN – ALL SUBJECTS ..................................... 38 
8.2 
STUDY ENROLLMENT ............................................................................... 43 
8.3 
INVESTIGATOR QUALIFICATION AND TRAINING ..................................... 43 
8.4 
SELECTION AND SCREENING OF SUBJECTS ............................................. 44 
8.5 
BASELINE ASSESSMENT: VISIT 1 (DAY 0-14) – ASSESSED DAY 14 ......... 44 
8.6 
BASELINE ASSESSMENT: VISIT 2 (DAY 15-30) – (+45 DAYS) .................. 45 
8.7 
BASELINE ASSESSMENTS VISIT 3 (DAY OF PROCEDURE) – 
ASSESSED ON DAY OF PROCEDURE .......................................................... 45 
8.8 
BASELINE ANGIOGRAM ............................................................................ 45 
8.9 
MOBIUSHD PROCEDURE.......................................................................... 46 
8.10 
POST-PROCEDURE CARE ......................................................................... 47 
8.11 
SUBJECT DISCHARGE ............................................................................... 48 
8.12 
7-DAY FOLLOW-UP VISIT (+2 / -3 DAYS) ................................................. 48 
8.13 
30-DAY FOLLOW-UP VISIT (+7 / -7 DAYS) ............................................... 48 
8.14 
90-DAY FOLLOW-UP VISIT (+14 / -14 DAYS) ........................................... 48 
8.15 
180-DAY FOLLOW-UP VISIT (+14 / -14 DAYS) ......................................... 49 

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8.16 
365-DAY FOLLOW-UP VISIT (+14 / -14 DAYS) ......................................... 49 
8.17 
LONG TERM FOLLOW-UP VISITS - 18, 24, 30, AND 36-MONTH 
FOLLOW-UP VISIT (+14 / -14 DAYS) ......................................................... 49 
8.18 
UNSCHEDULED FOLLOW-UP VISIT........................................................... 49 
8.19 
SCHEDULE OF STUDY VISITS AND ASSESSMENTS .................................... 49 
9.0 
STUDY COMPLETION .................................................................................... 50 
10.0 
CONCOMITANT MEDICATIONS ................................................................. 51 
11.0 
ADVERSE EVENTS .......................................................................................... 52 
11.1 
DEFINITIONS OF ADVERSE EVENTS .......................................................... 52 
11.1.1 Serious Adverse Events (SAE) ............................................................. 52 
11.2 
ADVERSE EVENT ASSESSMENT AND DOCUMENTATION .......................... 53 
11.2.1 CLASSIFICATION OF ADVERSE EVENTS BY INTENSITY/SEVERITY ......... 54 
11.2.2 EXPECTEDNESS ......................................................................................... 54 
11.2.3  RELATEDNESS ........................................................................................... 55 
11.2.4 OUTCOME ................................................................................................. 55 
11.2.5 TREATMENT OR ACTION TAKEN ............................................................. 55 
11.3 
ANTICIPATED ADVERSE EVENTS ............................................................. 55 
11.4 
SERIOUS ADVERSE EVENT AND UNANTICIPATED ADVERSE 
DEVICE EFFECT REPORTING ................................................................... 56 
11.5 
INDEPENDENT ADJUDICATION OF CLINICAL OUTCOME EVENTS 
BY DSMB .................................................................................................. 57 
12.0 
ETHICS AND REGULATORY CONSIDERATIONS ................................... 57 
12.1 
SUBJECT INFORMATION AND CONSENT PROCEDURES ............................ 57 
12.2 
IRB/EC APPROVAL .................................................................................. 57 
13.0 
STATISTICAL METHODS .............................................................................. 57 
14.0 
RECORDS AND REPORTS ............................................................................. 58 
14.1 
RECORDS .................................................................................................. 58 
14.2 
REPORTS ................................................................................................... 58 
15.0 
DATA MANAGEMENT .................................................................................... 58 
16.0 
MONITORING OF THE STUDY AND QUALITY CONTROL .................. 58 
16.1 
DSMB ....................................................................................................... 58 
16.2 
DATA COLLECTION AND MONITORING ................................................... 58 
16.3 
SOURCE DOCUMENTATION ...................................................................... 59 
16.4 
SITE COMPLIANCE / DEVIATIONS ............................................................ 59 
16.5 
MONITORING PLAN .................................................................................. 60 
17.0 
DATA MANAGEMENT .................................................................................... 60 

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17.1 
RECORD RETENTION ................................................................................ 60 
18.0 
PROTOCOL AMENDMENTS ......................................................................... 61 
19.0 
PROTOCOL DEVIATIONS ............................................................................. 61 
20.0 
DEVICE ACCOUNTABILITY ......................................................................... 61 
21.0 
INFORMED CONSENT PROCESS................................................................. 61 
22.0 
PREMATURE STUDY TERMINATION ........................................................ 62 
23.0 
REGULATORY AND HEALTH AUTHORITY AUDITS ............................ 63 
24.0 
SUBJECT PRIVACY AND CONFIDENTIALITY ........................................ 63 
25.0 
BIBLIOGRAPHY ............................................................................................... 64 
 
TABLE 1: CLASSIFICATION OF BLOOD PRESSURE (BP) .......................................................... 17 
TABLE 2:  CLASSIFICATION AND MANAGEMENT OF BLOOD PRESSURE FOR ADULTS .......... 20 
TABLE 3: CLINICAL TRIAL AND GUIDELINE BASIS FOR COMPELLING INDICATIONS FOR 
INDIVIDUAL DRUG CLASSES ..................................................................................... 21 
TABLE 4: MOBIUSHD IMPANT CHARACTERISTICS ................................................................. 24 
TABLE 5: COMPONENTS AND MATERIALS IN THE DC ............................................................ 27 
TABLE 6:  DC KEY MEASUREMENTS ........................................................................................ 27 
TABLE 7: SCHEDULE OF STUDY VISITS AND ASSESSMENTS ................................................... 50 
  
 
 
Figure 1: MobiusHD™ ............................................................................................................. 24 
Figure 2: MobiusHD Size A, as example ................................................................................. 25 
Figure 3: Actuation of Delivery Catheter ............................................................................... 26 
Figure 4: DC Key Measurements ............................................................................................ 28 
Figure 5: Enrollment Schedule for First 10 Study Subjects (Unilateral Treatment) ......... 29  
Figure 6:  Enrollment Schedule for an Additional 10 Study Subjects  
(Bilateral Treatment) ............................................................................................... 30 
Figure 7: Study Flow Chart Unilateral Cohort (N=10 Subjects) .......................................... 31 
Figure 8: Study Flow Chart Bilateral Cohort (N=10 Subjects) ............................................ 32 
 
Appendix I:    
 Imaging Guidelines 
Appendix II:   
 Sample Informed Consent Form 
Appendix III: 
 Sample Case Report Forms 
Appendix IV:       
 BP Measurement Instructions 
Appendix V:      
 Carotid Sinus Massage Instructions 
Appendix VI:     
 Instructions for Use 
Appendix VII:            Guidelines for the Six-Minute Walk Test 

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ACRONYMS 
 
 
ABPM 
Ambulatory Blood Pressure 
Monitoring 
ABS 
Acrylonitrile butadiene styrene 
AE 
Adverse Event 
BMI 
Body Mass Index 
BP 
Blood Pressure 
CAS 
Carotid Artery Stenting 
CBC 
Complete Blood Count 
CEA 
Carotid Endarterectomy 
CCA 
Common Carotid Artery 
CRF 
Case Report Form 
CVA 
Cerebrovascular Accident 
DBP 
Diastolic Blood Pressure 
DVT 
Deep Venus Thrombosis 
DC 
Delivery Catheter 
DSMB 
Data Safety Monitoring Board 
ECA 
External Carotid Artery 
EF 
Ejection Fraction 
GFR 
Glomerular filtration rate 
ICA 
Internal Carotid Artery 
ICD 
Informed Consent Document 
ICF 
Informed Consent Form 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
PEEK 
Polyetheretherketone 
PTFE 
Polytetrafluoroethylene 
PI 
Principal Investigator 
SBP 
Systolic Blood Pressure 
TIA 
Transient Ischemic Attack 

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DEFINITIONS 
Cerebrovascular accident (CVA) or stroke: Focal irreversible brain injury with neuron cell 
death most commonly caused by compromise of end-organ oxygen supply due to 
parenchymal hemorrhage from loss of arterial vascular integrity or flow interruption from 
intracranial arterial occlusion. 
Transient ischemic attack (TIA):  Focal neurological symptoms that resolve spontaneously 
within 24 hours without evidence of cerebral infarction. 
Secondary hypertension: High blood pressure that is caused by an identifiable secondary 
medical condition or exogenous substrate. Secondary hypertension differs from the usual 
type of high blood pressure (essential hypertension), which is often referred to simply as 
high blood pressure. Essential hypertension, also known as primary hypertension, has no 
clear cause and is thought to be linked to genetics, poor diet, lack of exercise and obesity. 
Secondary hypertension has been linked to conditions that affect kidney function, as well as 
sleep apnea, renal circulation compromise, congenital aortic abnormalities, unusual 
adrenalin secreting tumors, and endocrine system abnormalities.  In addition, the 
aggravating factor for secondary hypertension could also be medications like NSAIDs.  
Vulnerable plaque: An atheromatous plaque in an arterial wall that has abundant 
macrophages, prominent lipid pool, and is usually covered by a thin fibrous cap that is 
providing a limiting protective barrier from rupture. The repeated cycle of rupture and 
healing is regarded as one of the key mechanisms of arterial stenosis progression in 
atherosclerotic heart disease, myocardial infarction and strokes. 
Clinical significant structural valvular cardiac disease: For the purpose of this study we 
define a “significant” valvular condition as any structural heart abnormality that increases 
the patient’s risks for a stroke or adverse event during the follow-up period. For example, 
patients with hemodynamically significant aortic stenosis as defined by a mean gradient of > 
30mmHg and/or symptoms of dyspnea, chest pain or syncope.  In addition, this includes 
patients with moderate to severe mitral stenosis based on contemporary echo or 
hemodynamic guidelines. 
Moderate to severe reactive airway disease: 
Moderate persistent asthma: Documented primary reactive airway disease with 
symptoms that occur daily.  In addition, flare-ups can occur, increasing the 
symptoms from moderate to severe, which often last several days. Thus any patient 
with chronic daily symptoms and or documented flair-ups over the last year falls in 
this exclusion definition. Coughing and wheezing may disrupt the normal activities 
and make it difficult to sleep. Nighttime flare-ups may occur more than once a week. 
In moderate persistent asthma, lung function is roughly between 60% and 80% of 
normal, without treatment. 
Severe persistent asthma: With severe persistent asthma, symptoms occur daily and 
often. They also frequently curtail the patient’s activities or disrupt his/her sleep. 
Lung function is generally less than 60% of the normal level without treatment. 
History of hospitalization within the preceding year for an asthmatic attack is also 
consistent with severe asthma. 
 
 

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Moderate to severe COPD: 
Moderate COPD: For the purpose of this study, moderate COPD will be defined as 
any patient with documented chronic lung disease that experiences daily dyspnea 
symptoms and requires daily medical treatment in order to maintain normal daily 
activities.   
Severe COPD: Any patient with documented COPD on lung function and/or X-ray 
studies that has persistent limiting symptoms due to dyspnea. In addition these 
patients frequently have orthopnea that would prohibit them from lying flat during 
the needed imaging and transcatheter study device placement. This will also include 
any patient who has been hospitalized with acute exacerbation of COPD in the 
preceding year. 
Moderate to severe primary pulmonary hypertension: Any patient with symptoms of 
dyspnea and known pulmonary hypertension without secondary cause of recurrent 
pulmonary embolism, sleep apnea, left sided heart failure, chronic lung disease or other 
primary substrate. Objectively this can be defined as NYHA II or III symptoms with mPAP 
>41mmhg, or PASP >49 in the absence of a secondary cause.  
 
 
 
 
 
 
 

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1.0 
PROTOCOL SYNOPSIS 
 
TITLE 
CALM-FIM _US - Controlling and Lowering Blood Pressure  
with the MobiusHD™ - A Prospective Multicenter Safety Study 
STUDY 
OBJECTIVE 
To evaluate the safety and performance of the MobiusHD system in subjects 
with resistant hypertension. 
STUDY 
DESIGN 
This is an open-label, multicenter, first-in-man clinical trial to be conducted 
inside the United States.  Eligible subjects with stage 2 resistant systemic 
arterial hypertension currently being treated with a minimum of three (3) 
anti-hypertensive drugs, who consent to study participation will be assigned 
to treatment with the MobiusHD system. 
Potential study participants will be consented and then screened at two (2) 
baseline visits beginning at least 30 days prior to MobiusHD placement.  
Qualified patients will undergo placement of the MobiusHD under 
angiographic visualization, and will then be followed for 36 months. 
Subjects will be enrolled in two (2) phases, as follows: 
 Ten subjects will be implanted unilaterally and followed for seven 
(7) days. 
 Based on consensus following 7-day clinical outcome analysis by an 
independent data safety monitoring board (DSMB), 10 additional 
subjects will be enrolled and implanted bilaterally. 
PATIENT 
POPULATION 
Subjects with resistant hypertension receiving at least three (3) anti-
hypertensive medications including a diuretic and with no evidence of 
extracranial carotid disease or significant great vessel/aortic arch 
atherosclerotic disease. 
NUMBER OF 
PATIENTS 
Twenty subjects are to be enrolled at two (2) to ten (10) U.S. clinical sites. 
PRIMARY 
OUTCOME 
Safety: Incidence of serious adverse events (SAEs) and unanticipated 
adverse device effects (UADE) reported for the study population from 
implantation through six (6) months of follow-up.   
SECONDARY 
OUTCOME 
Performance:  Decrease in office cuff blood pressure (BP).  
 
ADDITIONAL 
OUTCOMES 
Change in heart rate 
Reduction of medication post 6-month follow-up 
365-Day safety and efficacy 
Long term safety and efficacy – one (1) to three (3) years 
 
 

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INCLUSION 
CRITERIA 
 
 
Baseline Screening Visit 1 – (Day 0 – 14) – Assessed on Day 14 
1. Provided written informed consent; 
2. ≥ 18 years of age and ≤ 80 years of age; 
3. Office cuff SBP ≥ 160 mmHg measured per protocol instructions 
(Appendix IV) following at least one (1) month of maximally 
tolerated therapy with at least three (3) anti-hypertensive 
medications, of which at least one (1) must be a diuretic.  Any 
combination medications will be counted per the active 
ingredient. (For example, Zestoretic (Lisinopril +HCTZ) equals 
two (2) anti-hypertensive medications);  
4. Renal artery imaging performed within the last 12 months 
showing no evidence of renal artery stenosis. Acceptable imaging 
modalities include renal duplex, magnetic resonance angiography, 
CT angiography, and selective or nonselective renal angiography 
depending on trial site diagnostic standards. In the absence of 
adequate imaging testing this inclusion criteria could also be met 
by obtaining a renal duplex prior to enrollment, or by performing 
nonselective renal angiography at the time of device implantation. 
5. Compliant with medications (self-reported) and daily blood 
pressure readings – Subject must be minimum 80% complaint 
with diary entries; and 
6. For females (with child-bearing potential), a negative pregnancy 
test, and the use of a medically accepted method of birth control 
for the duration of the trial. 
 
Baseline Screening Visit 2 – (Day 15 – 30) - Assessed on Day 30  
1. No significant obstructive vascular disease or plaque on CTA or 
MRA of the aortic arch and great vessels; 
2. Carotid duplex studies demonstrating no obstructive carotid 
disease or plaque;  
3. Continued adherence to hypertension medications without 
anticipated changes and daily blood pressure readings – Subject 
must be a minimum 80% compliant with diary entries; and 
4. Continued office cuff SBP ≥ 160 mmHg despite at least one (1) 
month of maximally tolerated therapy with at least three (3) anti-
hypertensive medications, of which at least one (1) must be a 
diuretic. Any combination medications will be counted per the 
active ingredient. (For example, Zestoretic (Lisinopril+HCTZ) 
equals two (2) anti-hypertensive medications). 
Day of Procedure - 
1. Continued adherence to hypertension medications without 
anticipated changes and daily blood pressure readings – Subject 
must be a minimum 80% compliant with diary entries. 
 
 
 

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EXCLUSION 
CRITERIA 
Baseline Screening Visit 1 – (Day 0 – 14) – Assessed on Day 14  
1. Known or clinically suspected baroreflex failure or autonomic 
neuropathy; 
2. Hypertension secondary to an identifiable and treatable cause 
other than sleep apnea (e.g., hyperaldosteronism, renal artery 
stenosis, pheochromocytoma, Cushing's disease, coarctation of the 
aorta, hyperparathyroidism and intracranial tumor); 
3. Treatable cause of resistant 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, sympathomemetics, oral 
contraceptives (confirmed cause of resistant hypertension),  
adrenal steroids, cyclosporine, and tacrolimus, erythropoietin, 
licorice (including some chewing tobacco), ephedra, ma haung, 
bitter orange); and excessive alcohol intake; 
4. Arm circumference greater than 46cm and/or BMI ≥ 40; 
5. Chronic atrial fibrillation or recurrent atrial fibrillation with 
episode within the last 12 months; 
6. Vulnerable plaque or ulceration of any size in the carotid artery or 
aortic arch; 
7. History of bleeding complications with dual anti-platelet therapy 
in the past or has known uncorrectable bleeding diathesis; 
8. Current use of additional anticoagulation therapy. Examples 
include vitamin K antagonists like warfarin, direct thrombin 
inhibitors, direct factor Xa inhibitors, thrombin IIa inhibitors like 
apixaban, rivaroxaban, dabigatran and etexilate; 
9. Peptic ulcer disease with documented active ulcer or bleeding 
within the last year. 
10. History of allergy to contrast dye that cannot be managed 
medically; 
11. History of orthostatic hypotension; 
12. History of syncope within the last six (6) months; 
13. History of myocardial infarction or unstable angina within the past 
three (3) months; 
14. History of cerebral vascular accident (stroke or TIA) within the 
past year; 
15. Severe chronic kidney disease (calculated GFR < 45 ml/min);  
16. Prior surgery, radiation, or endovascular stent placement in either 

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carotid region; 
17. Clinically significant structural valvular cardiac disease; 
18. Moderate to severe reactive airway disease, chronic obstructive 
pulmonary disease, or primary pulmonary hypertension; 
19. Uncompensated congestive heart failure or known severe 
reduction in left ventricular function (EF < 30%); 
20. Uncontrolled co-morbid medical condition that would adversely 
affect participation in the trial; 
21. Non-controlled diabetes mellitus;  
22. Active infection within the last month; 
23. Co-morbid condition that reduces life expectancy to less than one 
(1) year; 
24. Mental health issues that would prohibit the subject’s availability 
to meet the Protocol requirements; 
25. Currently taking an imidazoline receptor agonist or central 
sympathetic treatment; 
26. Enrolled in a concurrent clinical trial;  
27. Unable or unwilling to fulfill the protocol follow-up requirements;  
28. Subject is a prisoner or member of other protected population;  
29. Planned surgery or other procedure within the next six (6) months;  
30. Deep venous thrombosis (DVT) within the last year or 
documented recurrent DVT. 
 
Baseline Screening Visit 2 – (Day 15 – 30) - Assessed on Day 30  
1. ICA lumen diameters < 5 mm or > 11.75 mm  within the planned 
location of the device placement via CTA or MRA;  
2. Carotid hypersensitivity detected by carotid massage or typical 
history, as described in the Protocol (Appendix V); or 
3. Significant aortoiliac or common femoral artery disease that will 
prohibit safe femoral access. 
 
Day of Procedure – Angiographic 
1. Evidence of plaque, ulceration or any stenosis on selective carotid 
angiography performed in orthogonal views. Lumen diameters 
will be assessed to exclude subjects with ICA lumen diameters 
smaller than 5 mm or larger than 11.75 mm within the planned 
location of the device placement; 
2. Any angiographic evidence of plaque or ulceration in the aortic 
arch and/or the supra aortic vasculature;  

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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; or 
4. Type III arch or horizontal takeoff of the left carotid from the 
innominate and any calcification of the carotid bulb. 
 
 

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STUDY 
ENROLLMENT 
This study will be enrolled based on the following matrix with review of 
Data Safety Monitoring Board (DSMB) and FDA: 
 
Unilateral study safety design: 
 
 
Following enrollment of the initial 10 subjects, based on DSMB review of 
available data, a determination will be made on whether the safety of the 
MobiusHD is adequate to support bilateral placement.  If the DSMB 
determines that bilateral treatment is warranted, an interim report with all 
available clinical data will be submitted to FDA with a request for initiation 
of bilateral treatment in the remaining 10 study subjects. 
  
Bilateral study design: (if approved by DSMB and FDA) 
 
 
Subject 1 
•DSMB review of 7-day data 
Subject 2-5 
•DSMB review of 7-day data 
Subject 6-10 
•DSMB review of 7-day data of subjects 6-10 
•Data submitted to FDA for approval of dose escalation to 
bilateral implantation or continued unilateral implantation of 
subjects 11-20 
Subject 11 
•DSMB review of 7-day data 
Subject 12-
15 
•DSMB review of 7-day data 
Subject 16-
20 
•DSMB review of 7-day data of subject 16-20 

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2.0 BACKGROUND AND INTRODUCTION 
Normal or optimal blood pressure (BP) is defined as the level at which minimal vascular 
damage occurs. The Joint National Committee 7 (JNC 7) defines normal BP as a systolic BP 
(SBP) less than 120 mmHg and diastolic BP (DBP) less than 80 mmHg.1  
An estimated 76 million adults above the age of 20 have high blood pressure in the United 
States. Data from NHANES 1999-2006 found that approximately 8% of US adults have 
undiagnosed hypertension. Approximately 30% of adults are unaware of their hypertension, 
greater than 40% are not on any treatment and two-thirds of hypertensive patients are not 
being controlled to BP levels <140/90 mmHg.1 The highest prevalence of hypertension in 
the US is noted in African Americans. 
Worldwide prevalence estimates indicate that hypertension may affect as many as 1 billion 
individuals, and approximately 7.1 million deaths per year may be attributable to 
hypertension.1 The World Health Organization reports that suboptimal BP (>115 mmHg 
SBP) is responsible for 62% of cerebrovascular disease and 49% of ischemic heart disease 
(IHD), with little variation by sex. In addition, suboptimal BP is the number one attributable 
risk factor for death throughout the world.1 
Blood pressure control rate is recognized to be suboptimal in those who have serious 
comorbid conditions like chronic kidney disease. In a survey of patients in the United States 
with chronic kidney disease, BP control was found to be a dismal 13.2%.2  On a global level, 
hypertension is an even greater problem, with 13.5% of all deaths attributed to BP-related 
diseases. A majority of those who carry this disease burden belong to lower economic 
strata.3 
It is clearly recognized that increased BP is associated with a greater risk of heart attack, 
stroke, and kidney disease. In fact, for persons aged 40 to 70 years, each increment of 
20 mmHg in SBP or 10 mmHg in DBP actually doubles the risk of cardiovascular disease 
across the entire range of BP, from 115/75 to 185/115 mmHg.4  
TABLE 1: CLASSIFICATION OF BLOOD PRESSURE (BP) 
Classification 
Systolic BP (mmHg) 
Diastolic BP (mmHg) 
Normal 
<120 
And <80 
Prehypertension 
120-139 
Or 80-89 
Stage 1 hypertension 
140-159 
Or 90-99 
Stage 2 hypertension 
>160 
Or >100 
BP, blood pressure data from http://www.nhlbi.nih.gov/guidelines/hypertension/index.htm (accessed April 12, 2012). 
 
Based on JNC 7, patients with sustained hypertension are further divided into stage 1 
hypertension (SBP 140-159 mmHg or DBP 90-99 mmHg), stage 2 hypertension  
(SBP >160 mmHg or DBP >100 mmHg), and those with compelling indications that include 
diabetes, cardiovascular disease, and renal disease. Each BP increase of 20/10 mmHg 
doubles the risk of cardiovascular death. 
 
 

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Hypertension remains uncontrolled in the majority of treated patients, especially those with 
multiple cardiovascular risk factors. This was demonstrated by a French study that showed 
that 70% of treated hypertensive patients are not controlled to the target level of  
140/90 mmHg. This proportion reached 84% in hypertensive patients with diabetes (target 
level 130/85 mmHg). 
Resistant hypertension is a widely prevalent condition, estimated to affect approximately 
30% of the population in the United States. Resistant hypertension is defined as elevated BP 
that remains despite treatment with at least three (3) anti-hypertensive agents at optimal 
doses.  The morbidity and mortality risks associated with hypertension support the need for 
evaluation of new therapies that can reduce or eliminate the challenges of side effects and 
poor long-term compliance associated with commercially available blood pressure-lowering 
medications. 
2.1  
CURRENT HYPERTENSION TREATMENT 
2.1.1   Lifestyle Modification 
Educating patients regarding the importance of non-pharmacologic interventions for 
effective BP control is an important component of reducing cardiovascular risk in the 
general population. This is particularly true for the pre-hypertensive and hypertensive 
patient. Aggressive efforts, however, are needed to ensure optimal adherence to 
recommendations. 
Lifestyle modifications include limiting alcohol intake, increasing physical activity, and 
reducing sodium intake to less than 6 g of sodium chloride daily. Results from the long-term 
follow-up of the Trials of Hypertension Prevention (TOHP) study demonstrated that patients 
who were randomized to a low-salt diet (sodium <1800 mg/24 hr) had a 25% risk reduction 
in cardiovascular events.5 
Weight reduction of as little as 10 to 12 pounds in the obese hypertensive patient can have a 
considerable impact on elevated BP. Appropriate nutritional counseling can encourage a diet 
with reduced total fat and cholesterol intake, in addition to providing an adequate daily 
intake of potassium, calcium, and magnesium. The Dietary Approaches to Stop 
Hypertension (DASH) trial has provided substantial data that a diet rich in fruits, nuts, 
vegetables and low-fat dairy products, with an emphasis on fish and chicken rather than red 
meat, contributed to lowered BP, even without weight reduction. This dietary approach was 
particularly effective for participants who also restricted sodium chloride intake.6  Dietary 
recommendations must be made on an individualized basis and should be well supported 
with continued educational and counseling efforts. 
Cigarette smoking is a recognized accelerator of cardiovascular disease. Smoking cessation 
should, therefore, be strongly encouraged for all patients, and education, counseling, and 
medication should be provided as needed. 
The effects of implementing these modifications are both dose-dependent and time-
dependent and could be greater for some patients than for others. Also, a combination of two 
or more lifestyle modifications can lead to even better results. Lifestyle modifications not 
only reduce BP but also enhance the efficacy of antihypertensive drugs and decrease 
cardiovascular risk. 

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2.1.2    Medical Treatment for Stage 1 and Stage 2 Hypertension  
Based on Antihypertensive and Lipid Lowering to Reduce Heart Attack Trial (ALLHAT) 
data, JNC 7 recommends diuretics as first-line therapy for the management of stage 1 
hypertension, and a combination of two (2) drugs as initial therapy for stage 2 hypertension, 
preferably with a diuretic as one (1) of these two (2) drugs.1 
It was concluded from this trial that diuretic therapy is as effective as a calcium channel 
blocker (CCB) or an angiotensin-converting enzyme (ACE) inhibitor from the standpoint of 
the primary outcome of the trial, and diuretic therapy is superior for select subgroup 
analyses. A critical look at the trial design suggests a more prudent conclusion that diuretics 
should be part of all antihypertensive regimens unless they are clearly contraindicated. 
In addition, there was a concern that diuretics might worsen glucose tolerance and insulin 
resistance. Recent data demonstrates that the higher incidence of diabetes mellitus related to 
thiazides does not appear to be responsible for the increase in risk for coronary heart 
disease.5 In addition to thiazide diuretics, JNC 7 guidelines also recommend ACE inhibitors, 
angiotensin receptor blockers (ARBs), beta-blockers (BBs), and CCBs as first-line therapy 
for hypertension. Since the publication of JNC 7 guidelines, studies have shown that beta-
blocker therapy might not be effective and in fact might increase the risk of stroke.1,4 In the 
newer guidelines published by various national societies, BBs have been removed as first-
line therapy and are recommended only with a compelling indication in those with cardiac 
disease. 
Based on evidence of improved outcomes, JNC 7 has recommended several medications for 
compelling indications (Tables 2 and 3). These include BBs and aldosterone antagonists in 
those with cardiac disease, ACE inhibitors and ARBs in those with chronic kidney disease, 
and diuretics and CCBs in those with isolated systolic hypertension. A combination of ACE 
inhibitors and diuretics instead of ACE inhibitors alone is recommended for preventing 
recurrence of stroke based on findings of the Perindopril Protection Against Recurrent 
Stroke Study (PROGRESS), which showed a 42% stroke reduction in those treated with this 
combination of therapy.7 
 
 

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TABLE 2: CLASSIFICATION AND MANAGEMENT OF BLOOD PRESSURE FOR ADULTS 
 
 
 
 
Initial Drug Therapy 
BP Classification SBP,* 
mmHg 
DBP,* 
mmHg 
Lifestyle 
Modifications 
With Compelling 
Indications 
Without Compelling 
Indications 
Normal 
<120 
and <80 
Encourage 
 
 
Prehypertension 120-139 
Or 80-89 
Yes 
No antihypertensive 
drug indicated 
Drug(s) for 
compelling 
indications† 
Stage 1 
Hypertension 
140-159 
Or 90-99 
Yes 
Thiazide-type diuretics 
for most. May consider 
ACEI, ARB, BB, 
CCB, or combination 
Drug(s) for the 
compelling 
indications.‡ Other 
antihypertensive 
drugs (diuretics, 
ACEI, ARB, BB, 
CCB) as needed 
Stage 2 
Hypertension 
>160 
Or >100 
Yes 
Two-drug combination 
for most† (usually 
thiazide-type diuretic 
and ACEI or ARB or 
BB or CCB) 
 
 
Data from Chobanian AV, Bakris GL, Black HR, et al; Joint National Committee on Prevention, Detection, Evaluation, and 
Treatment of High Blood Pressure; National Heart, Lung, and Blood Institute; National High Blood Pressure Education 
Program Coordinating Committee: Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, 
and Treatment of High Blood Pressure. Hypertension 2003;42(6):1206-1252. Available at 
http://www.nhlbi.nih.gov/guidelines/hypertension/index.htm (accessed April 12, 2012). 
*Treatment determined by highest blood pressure category. †Initial combined therapy should be used cautiously in those at risk for 
orthostatic hypotension. ‡Treat patients with chronic kidney disease or diabetes to blood pressure goal of;130/80 mmHg. ACEI, 
angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BB, beta blocker; CCB, calcium channel blocker; DBP, 
diastolic blood pressure, SBP, systolic blood pressure. 
 
 
 

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TABLE 3: CLINICAL TRIAL AND GUIDELINE BASIS FOR COMPELLING  
INDICATIONS FOR INDIVIDUAL DRUG CLASSES 
 
Recommended Drugs 
 
Compelling 
Indication* 
Diuretic BB ACEI ARB 
CCB Aldo ANT 
Clinical Trial Basis† 
Heart failure 
√ 
√ 
√ 
√ 
 
√ 
ACC/AHA heart failure 
guideline, MERIT-HF, 
COPERNICUS, CIBIS, 
SOLVD, AIRE, TRACE, 
ValHEFT, RALES 
Post-myocardial 
infarction 
 
√ 
√ 
 
 
√ 
ACC/AHA post-MI guideline, 
BHAT, SAVE, Capricorn, 
EPHESUS 
High coronary 
disease risk 
√ 
√ 
√ 
 
√ 
 
ALLHAT, HOPE, ANBP2, 
LIFE, CONVINCE 
Diabetes 
√ 
√ 
√ 
√ 
√ 
 
NKF-ADA guideline, UKPDS, 
ALLHAT  
Chronic kidney 
disease 
 
 
√ 
√ 
 
 
NKF guideline, captopril trial, 
RENAAL, IDNT, REIN, AASK 
Recurrent stroke 
prevention 
√ 
 
√ 
 
 
 
PROGRESS 
 
Data from Chobanian AV, Bakris GL, Black HR, et al; Joint National Committee on Prevention, Detection, Evaluation, and 
Treatment of High Blood Pressure; National Heart, Lung, and Blood Institute; National High Blood Pressure Education 
Program Coordinating Committee: Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, 
and Treatment of High Blood Pressure. Hypertension 2003;42(6):1206-1252. Available at 
http://www.nhlbi.nih.gov/guidelines/hypertension/index.htm (accessed April 12, 2012). 
*Compelling indications for antihypertensive drugs are based on benefits from outcome studies or existing clinical guidelines; the 
compelling indication is managed in parallel with the BP. 
†Conditions for which clinical trials have demonstrated benefit of specific classes of antihypertensive drugs. ACEI, angiotensin-converting 
enzyme inhibitor; Aldo ANT, aldosterone antagonist; ARB, angiotensin receptor blocker; BB, beta blocker; CCB, calcium channel blocker. 
 
2.1.3   Baroreceptor Modulation for Hypertension 
The pivotal role of the autonomic nervous system in the pathogenesis of hypertension is well 
established.  However, pharmacological therapies that block sympathetic activity have not 
achieved the desired outcomes. 
In the past few years, there have been efforts to develop medical devices and techniques that 
influence sympathetic nervous system activity.  These include endovascular renal 
sympathetic denervation and continuous electrical baroreceptor nerve pacing. 

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Vascular Dynamics’ approach is to modulate the baroreflex using a simple, passive, 
implantable device as a means for inhibiting sympathetic activity and lowering BP. The 
application of localized mechanical forces to the arterial wall of the carotid sinus changes its 
geometric shape to increase baroreceptor signaling, while preserving arterial pulsatility and 
blood flow.    
The effect of a change in the morphology of the carotid sinus on systemic BP has been 
studied in dogs, both acutely by Bagshaw, et. al. (1987)8, and chronically by Fadali, et. al. 
(1969).9  In both studies, the canine carotid sinuses were surgically enlarged using a vein 
patch.  Bagshaw measured the effect this “patchplasty” had on systemic BP and found that 
the increase in carotid baroreceptor sensitivity correlated with the increase in the diameter of 
the sinus.  In the chronic study by Fadali, the dogs’ systemic BP was lowered significantly 
over a follow-up period of six (6) months. 
Although the exact change in carotid sinus morphology in the studies described above is 
different from the one produced by the MobiusHD, these studies clearly demonstrate that an 
artificial increase in the diameter of the carotid sinus, which preserves the pulsatile nature of 
the input to the baroreceptors, increases the strain measured by the baroreceptors and 
ultimately reduces systemic BP.  This is especially relevant to the MobiusHD’s mechanism 
of action since the enlarged diameter in these studies was produced by a surgical change 
rather than as a result of mere over-inflation of the sinus by increased internal pressure. 
A study in human subjects by McKevitt, et. al. (2003)10 investigated the short and long term 
effects of carotid endarterectomy (CEA) and carotid artery stenting (CAS) on systemic 
arterial BP.  A statistically significant decrease in SBP was found at one and six months only 
in the surgical group (37 subjects) but not in the CAS group (40 subjects).  Acute 
hypotension was observed in both groups.  These findings support our hypothesis that 
traditional carotid stents cause only transient hypotension due to an exaggerated stretching 
of the arterial wall, which reduces pulsatility and ultimately induces baroreceptor resetting.   
In a CEA the diameter of the carotid sinus is enlarged by use of a patch, and the cross 
section of the artery becomes non-circular, resulting in short-term hypotension11. 
Implantation of the MobiusHD also results in a change to the cross-sectional shape of the 
carotid sinus, but unlike a carotid stent or CEA, the MobiusHD maintains pulsatility. 
Knowledge derived from NASA’s research on the baroreflex in humans using the Variable 
Pressure Neck Chamber is described by Fadel, et. al.(2003).12  These experiments 
demonstrate the significant impact that mechanical modulation of the carotid sinus has on 
systemic BP in humans, and that this effect is mostly exerted through a change of systemic 
vascular resistance by the sympathetic nervous system. 
Based on data suggesting the potential utility of mechanical modulation of the baroreflex for 
lowering BP, Vascular Dynamics has developed the MobiusHD for the treatment of resistant 
hypertension.13 The MobiusHD, the subject of this protocol (Protocol), is a sterile self-
expanding nitinol implant, delivered through a disposable catheter, the Delivery Catheter.  
Together, the MobiusHD and Delivery Catheter make up the MobiusHD system. The 
MobiusHD is designed to treat drug-resistant hypertension by amplifying carotid sinus 
baroreceptor afferent signaling. 

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3.0 
MOBIUSHD™ SYSTEM 
3.1  
DETAILED DESCRIPTION OF MOBIUSHD 
The MobiusHD system consists of two parts: (1) the implant (MobiusHD); and (2) the 
Delivery Catheter (DC). The implant is a thin, flexible, open metal cage that is implanted in 
the carotid sinus. It is made of a nickel-titanium alloy (nitinol) tubing and laser-cut into a 
cage shape. Two radiopaque markers made of tantalum are welded at each end of the 
implant to help with visualization and positioning under fluoroscopy. The implant is 
mounted in a long, thin, tube-like device called a catheter, which together with the delivery 
handle, constitutes the Delivery Catheter.   
The MobiusHD system is compatible with appropriately sized commercially available 
guidewires and guiding catheters and/or sheaths.  The MobiusHD system is introduced into 
the femoral artery in the groin, and advanced through the length of the guiding catheter or 
sheath over a guidewire into the carotid sinus using fluoroscopic guidance.  
Once the Delivery Catheter has been guided to the desired location, the implant is partially 
deployed by holding the delivery handle stationary, while moving the lever to a secondary 
locked position.  At this point, the operator has the opportunity to review the position and 
recapture the device if repositioning is needed.  The recapture is performed by simply 
advancing the lever forward back to the closed position.  Alternatively, if the operator is 
pleased with the position, a second release maneuver is performed and with a final short 
lever retraction, the remaining constrained portion of the implant is allowed to expand and is 
released from the delivery system. The implant is designed to expand to a programmed size 
after being released from the delivery catheter.  
3.2 
COMPONENTS 
The MobiusHD system consists of two parts: (1) the implant (MobiusHD); and (2) the 
Delivery Catheter.   
 Implant – A super-elastic self-expanding nitinol open metal cage with two 
radiopaque markers on each end.  The implant expands as it is deployed from the 
delivery catheter.  The implant may be partially deployed and still be retracted back 
into its delivery catheter.  The implant is preloaded in the Delivery Catheter. 
 Delivery Catheter – A soft, atraumatically tipped delivery catheter with a delivery 
handle attached to its proximal end. The delivery handle has stops that allow for 
partial deployment without risk of unintended release of the implant. In addition 
there are locks that prevent premature unsheathing or device release.  When release 
is desired, the delivery handle must be further actuated to release the implant from 
the delivery catheter. 
 
The MobiusHD system is designed to track easily within the guiding catheter or sheath 
through the vasculature to the left or right carotid sinus located in the ICA just distal to the 
common carotid bifurcation. 
 
 

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3.2.1   MobiusHD (implant)  
The MobiusHD is laser cut from a tube of superelastic nitinol.  This is the same material 
used in most self-expanding stents.  After laser cutting, the implant is heat set to its final 
shape.   Radiopaque tantalum markers are swaged and welded into marker holes previously 
cut into the implant.  Finally, the implant is electropolished to create a smooth surface.   The 
design consists of four “windows,” which amplify carotid sinus baroreceptor afferent 
signaling, while maintaining pulsatility of the vessel.  The “crowns” at each end of the 
windows generate the radial force necessary for the implant to self-expand and allow the 
struts of the implant in the mid-body to maintain proper wall apposition, thus creating the 
wide “windows” necessary to amplify pulsatility.  To minimize the force per area, the struts 
along the main body of the implant are doubled to increase the surface area in order to 
distribute the radial force.  The implant design is illustrated in Figures 1 and 2 and its 
characteristics are presented in Table 4. 
 
 
 
FIGURE 1: MOBIUSHD™ 
 
 
TABLE 4: MOBIUSHD IMPLANT CHARACTERISTICS 
Characteristic 
Specification 
Length (unconstrained) 
17.00 to 19.30 mm 
Expanded Diameter 
5.00 to 11.75 mm 
Implant Coverage (%Surface Area) 
≤ 10.25% for all models 
 
 
 
 
 
 
 
 
 
 
 
 

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FIGURE 2: MOBIUSHD SIZE A, AS EXAMPLE 
 
 
 

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3.2.2   Delivery Catheter 
The Delivery Catheter (DC) is designed to enable the physician to navigate to the desired 
deployment location and accurately unsheathe the implant in a controlled fashion.  Similar 
to other commercially available devices, the DC is designed with a truncated central 
guidewire lumen (i.e. rapid exchange) to allow introduction over a standard length 0.014” 
guidewire.  The DC is comprised of an inner body and an outer body.  The delivery handle 
connects these two components and allows the user to controllably retract the outer body 
while maintaining the position of the implant in the desired deployment location.  This 
enables the implant to gently expand to meet the interior luminal vessel wall.  The additional 
control provided by the delivery handle reduces the risk associated with advancing the 
implant rather than retracting the outer body.  
In order to avoid unintentional deployment, the delivery handle incorporates features that 
require additional action on the part of the user to move from the partial deployment position 
to full deployment.  Additionally, the DC allows the physician to re-sheath and reposition 
the implant to ensure the desired placement is achieved. The actuation of the Delivery 
Catheter is illustrated in Figure 3. 
 
 
FIGURE 3: ACTUATION OF DELIVERY CATHETER 
 
Materials standard to commercially available medical devices have been employed  
in the construction of the Delivery Catheter.  These materials include Nylon-12, PEEK, 
Pebax, high density polyethylene (HDPE), 90% Platinum/10% Iridium, stainless steel (in the 
form of wire, tubing and machined components), ABS, and medical grade adhesives.  
Similarly, common processes are used for construction of the DC, including extrusion, 
thermal and adhesive bonding, conventional machining, injection molding and braiding. 
Components of the Delivery Catheter are listed in Table 5. Key measurements are presented 
in Table 6 and Figure 4. 
 

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TABLE 5: COMPONENTS AND MATERIALS IN THE DELIVERY CATHETER 
Catheter Component 
Material 
Patient Contact? 
Inner Extrusion 
PEEK 
Yes 
Atraumatic Tip 
Pebax 
Yes 
Support Coil 
Stainless Steel 
No 
Retractor 
Stainless Steel 
Yes 
Hypotube, Proximal 
Stainless Steel 
Yes 
Hypotube Cover 
HDPE 
Yes 
RX Adaptor 
Stainless Steel 
Yes 
Outer Shaft, Braided 
PTFE, Stainless Steel, 
Nylon-12, Pebax, 
Pt/Ir, PET 
Yes 
Handle, Top 
ABS, Ink 
No 
Handle, Bottom 
ABS 
No 
RHV Sheath 
PEEK 
No 
Shuttle, Handle 
ABS 
No 
Screw, Handle 
Stainless Steel 
No 
Standoff, Handle 
Stainless Steel 
No 
Cap, Handle 
ABS 
No 
Crimp Tube & Block 
Stainless Steel, 
Ag Solder 
No 
 
TABLE 6: DELIVERY CATHETER KEY MEASUREMENTS 
Characteristic 
Specification* 
RX Section Length 
35 cm 
Tri-Axial Section Length 
30 cm 
Working Length 
135 cm 
Guidewire Compatibility 
.014” 
Crossing Profile 
.078” Max 
Guide Catheter/Sheath 
Compatibility 
8 Fr Guide Catheter / 6 Fr Sheath with 
minimum inner diameter of .086”/2.18mm 
*All dimensions nominal 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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FIGURE 4: DELIVERY CATHETER KEY MEASUREMENTS 
 
 
3.3   
PRINCIPLE OF OPERATION 
The MobiusHD is placed in the target carotid sinus by advancing the catheter to the target 
site through the femoral artery, through an appropriate guiding catheter or sheath, and over a 
.014 inch guidewire.  This catheter houses the MobiusHD implant.  The catheter is precisely 
positioned in the carotid sinus using the marker bands on the DC and implant as a guide.  
When properly positioned, the DC protective sheath is pulled back by manipulation of the 
handle, to allow expansion of the implant and apposition with the vessel intima.  The 
catheter is then withdrawn, leaving the implant at the site of the carotid sinus. 
4.0 
STUDY OBJECTIVES 
The objective of the present study is to prospectively evaluate the safety of the MobiusHD 
system in subjects with resistant hypertension in a multi-center, open-label, first-in-man 
clinical trial. 
Additional goals of this study are to evaluate the effect of MobiusHD device on systemic 
blood pressure, diastolic blood pressure, and heart rate.  
5.0 
CLINICAL STUDY DESIGN 
This is an open-label, multicenter, first-in-man clinical trial to be conducted inside the 
United States.  Up to 20 patients with stage 2 resistant hypertension (i.e., inadequate blood 
pressure control with a minimum of three (3) anti-hypertensive drugs), who meet the 
protocol eligibility criteria and consent to study participation will undergo placement of the 
MobiusHD implant in the carotid sinus and will be followed for 36 months. 
 

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The first 10 patients enrolled will undergo unilateral placement of a single MobiusHD 
implant.  Enrollment of this group of 10 subjects will be staggered based on review of 
clinical outcomes by the Data Safety Monitoring Board (DSMB) and by FDA, as shown in 
Figure 5.   
 
 
FIGURE 5:  ENROLLMENT SCHEDULE FOR FIRST 10 STUDY SUBJECTS  
(UNILATERAL TREATMENT) 
 
Following enrollment of the initial 10 subjects, based on DSMB review of available data, a 
determination will be made on whether the safety of the MobiusHD is adequate to support 
bilateral placement.  If the DSMB determines that bilateral treatment is warranted, an 
interim report with all available clinical data will be submitted to FDA with a request for 
initiation of bilateral treatment in the remaining 10 study subjects. 
If bilateral placement of the MobiusHD is recommended by the DSMB and approved by 
FDA, enrollment will again be staggered as shown in Figure 6.  
 
 
 
 
 
Subject 1 
• DSMB Review of 7 day data 
Subject 2-5 
• DSMB Review of 7 day data 
Subject 6-
10 
• DSMB review of 7 day data of subjects 6-10 
• Data submitted to FDA for approval of bilateral implantation 
or continued unilateral implantation of subjects 11-20 

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FIGURE 6:  ENROLLMENT SCHEDULE FOR AN ADDITIONAL 10 STUDY SUBJECTS  
(BILATERAL TREATMENT) 
 
 
Flow charts for patient screening and enrollment are provided in Figure 7 and Figure 8, for 
the 10 subjects to be treated with a single device (Unilateral Cohort) and for the next 10 
subjects to receive devices bilaterally (Bilateral Cohort), respectively.  As shown, study 
subjects have two (2) screening visits for determination of eligibility, an initial screening 
visit (Day 0 to 14) and a second screening visit (Day 15 to 30), followed by a baseline visit. 
All study subjects will be examined on days 7, 30, 90, 180, 360, 1 year 6 months, 2 years,  
2 years 6 months, and 3 years.  
 
Subject 11 
•DSMB Review of 7 day data 
Subject 12 -
15 
•DSMB Review of 7 day data 
Subject 16-
20 
•DSMB review of 7 day data of subjects 16-20 

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FIGURE 7:  STUDY FLOW CHART UNILATERAL COHORT (N = 10 SUBJECTS) 
 

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FIGURE 8:  STUDY FLOW CHART BILATERAL COHORT (N = 10 SUBJECTS) 
 

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6.0 
STUDY POPULATION 
The study population for this clinical trial consists of male and female adults who have been 
diagnosed with stage 2 resistant hypertension, on at least three (3) anti-hypertensive 
medications of which one is a diuretic.  All potential study participants must meet all of the 
following eligibility criteria to qualify for enrollment in the study. 
6.1 
INCLUSION CRITERIA 
Candidates for this study must meet the following criteria to be enrolled in the study, as 
determined in the following screening and baseline visits:   
Baseline Screening Visit 1 – (Day 0 – 14) – Assessed on Day 14 
1. Provided written informed consent; 
2. ≥ 18 years of age and ≤ 80 years of age; 
3. Office cuff SBP ≥ 160 mmHg measured per protocol instructions (Appendix VI) 
following at least one (1) month of maximally tolerated therapy with at least three 
(3) anti-hypertensive medications, of which at least one (1) must be a diuretic.  Any 
combination medications will be counted per the active ingredient (for example, 
Zestoretic (Lisinopril +HCTZ) equals two (2) anti-hypertensive medications);  
4. Renal artery imaging performed within the last 12 months showing no evidence of 
renal artery stenosis. Acceptable imaging modalities include renal duplex, magnetic 
resonance angiography, CT angiography, and selective or nonselective renal 
angiography depending on investigator site diagnostic standards. In the absence of 
adequate imaging testing this inclusion criteria could also be met by obtaining a renal 
duplex prior to enrollment or by performing nonselective renal angiography at the 
time of device implantation. 
5. Compliant with medications (self-reported) and daily blood pressure readings – 
Subject must be a minimum 80% compliant with diary entries; and 
6. For females (with child-bearing potential), a negative pregnancy test and the use of a 
medically accepted method of birth control for the duration of the trial. 
 
Baseline Screening Visit 2 – (Day 15 – 30) - Assessed on Day 30  
1. No significant obstructive vascular disease on CTA or MRA of the aortic arch and 
great vessels; 
2. Carotid duplex studies demonstrating no obstructive carotid disease;  
3. Continued adherence to  hypertension medications without anticipated changes and 
daily blood pressure readings – Subject must be a minimum 80% compliant with diary 
entries;  
4. Continued office cuff SBP ≥ 160 mmHg despite at least one  
(1) month of therapy at maximally tolerated therapy with at least three (3) anti-
hypertensive medications, of which at least one (1) must be a diuretic.  Any 
combination medications will be counted per the active ingredient (for example, 
Zestoretic (Lisinopril +HCTZ) equals two (2) anti-hypertensive medications). 

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Day of Procedure -  
1. Continued adherence to hypertension medications without anticipated changes and 
daily blood pressure readings – Subject must be a minimum 80% compliant with diary 
entries. 
6.2 
EXCLUSION CRITERIA 
Candidates will be ineligible for enrollment in the study if any of the following conditions 
are identified at the screening or baseline visits: 
Baseline Screening Visit 1 – (Day 0 – 14) – Assessed on Day 14  
1. Known or clinically suspected baroreflex failure or autonomic neuropathy; 
2. Hypertension secondary to an identifiable and treatable cause other than sleep apnea 
(e.g.,  hyperaldosteronism, renal artery stenosis, pheochromocytoma, Cushing's 
disease, coarctation of the aorta, hyperparathyroidism and intracranial tumor); 
3. Treatable cause of resistant 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, 
sympathomemetics, oral contraceptives (confirmed cause of resistant hypertension), 
adrenal steroids, cyclosporine, and tacrolimus, erythropoietin , licorice (including 
some chewing tobacco), ephedra, ma haung, bitter orange); and excessive alcohol 
intake; 
4. Arm circumference greater than 46 cm and/or BMI ≥ 40; 
5. Chronic atrial fibrillation; 
6. Vulnerable plaque or ulceration of any size in the carotid artery or aortic arch; 
7. History of bleeding complications with dual anti-platelet therapy in the past or has 
known uncorrectable bleeding diathesis; 
8. Current use of additional anticoagulation therapy. Examples include vitamin K 
antagonists like warfarin, direct thrombin inhibitors, direct factor Xa inhibitors, 
thrombin IIa inhibitors like apixaban, rivaroxaban, dabigatran and etexilate; 
9. Peptic ulcer disease with documented active ulcer or bleeding within the last year; 
10. History of allergy to contrast dye that cannot be managed medically; 
11. History of orthostatic hypotension; 
12. History of syncope within the last six (6) months; 
13. History of myocardial infarction or unstable angina within the past  
three (3) months; 
14. History of cerebral vascular accident (stroke or TIA) within the past year; 
15. Severe chronic kidney disease (calculated GFR < 45 ml/min);  
16. Prior surgery, radiation, or endovascular stent placement in either carotid region; 

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17. Clinically significant structural valvular cardiac disease; 
18. Moderate to severe reactive airway disease, chronic obstructive pulmonary disease, or 
primary pulmonary hypertension; 
19. Uncompensated congestive heart failure or known severe reduction in left ventricular 
function (EF < 30%); 
20. Uncontrolled co-morbid medical condition that would adversely affect participation in 
the trial; 
21. Non-controlled diabetes mellitus;  
22. Active infection within the last month; 
23. Co-morbid condition that reduces life expectancy to less than one (1) year; 
24. Mental health issues that would prohibit the subject’s ability to meet the protocol 
requirements; 
25. Currently taking an imidazoline receptor agonist or receiving central sympathetic 
treatment; 
26. Enrolled in a concurrent clinical trial;  
27. Unable or unwilling to fulfill the protocol follow-up requirements;  
28. Subject is a prisoner or member of other protected population;  
29. Planned surgery or other procedure within the next six (6) months; or 
30. Deep venous thrombosis (DVT) within the last year or documented recurrent DVT. 
 
Baseline Screening Visit 2 – (Day 15 – 30) - Assessed on Day 30  
1. ICA lumen diameters < 5 mm or > 11.75 mm within the planned location of the 
device placement via CTA or MRA; 
2. Carotid hypersensitivity detected by carotid massage or typical history, as described in 
the study protocol; and  
3. Significant aortoiliac or common femoral artery disease that will prohibit safe femoral 
access. 
Day of Procedure – Angiographic  
1. Evidence of plaque, ulceration or any stenosis by angiographic evaluation in 
orthogonal views of the carotid artery. Lumen diameters will be assessed to exclude 
subjects with ICA lumen diameters smaller than 5 mm or larger than 11.75 mm within 
the planned location of the device placement; 
2. Any plaque or ulceration on the arch angiogram involving the aortic arch and/or the 
origin of the great vessels; 
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; and 

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4. Type III arch or horizontal takeoff of the left carotid from the innominate and 
calcification of the carotid bulb. 
 
 

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7.0 
SUBJECT ENROLLMENT 
Clinical site personnel will review the patient’s medical history for eligibility.  Potential 
candidates will be fully informed of the purpose of the study and the nature of the 
implantation procedure.  The implantation procedure will be described and its potential risks 
and benefits will be explained in detail.  Once the patient’s potential eligibility has been 
determined, the Investigator will discuss the study and ask the patient if they are interested 
in participating in the study. Patients who voluntarily agree to participate in the trial will be 
asked to sign and date the written Informed Consent Document (ICD).  The study will be 
explained to the patient in lay terms.  The ICD, approved by the site Institutional Review 
Board (IRB), must be signed by the potential study participant before he or she undergoes 
any study specific assessments.  A copy of the signed and dated ICD should be provided to 
the subject.  Failure to obtain a signed ICD prior to the procedure constitutes a protocol 
deviation.  Subjects must be informed that they may withdraw from the study at any time, 
and for any reason, and will continue to receive therapy as indicated by their physician. 
All subjects who meet the eligibility criteria and give written informed consent are 
considered enrolled in the study and must be entered into the electronic database for 
assignment of subject identification number.  This unique number identifies each Case 
Report Form (CRF) and should be used on all source documents so that study data is 
reported in anonymous form to protect subject confidentiality.   
A screen-failed subject refers to a subject who signed the approved ICD but failed to meet 
all the eligibility criteria.  There are no follow-up requirements for subjects who electively 
withdraw from the study prior to treatment.  The original ICD and a screening log will be 
maintained in the clinical site’s study files.  No CRFs are required to be completed for 
screen failure patients and these patients will not be followed per the Investigational Plan 
requirements. 
If the Investigator is unable to place a MobiusHD implant in a subject, the subject will be 
followed to the 30-Day visit and will then be exited from the study in the absence of any 
ongoing adverse events.  If an adverse event is ongoing or not stabilized, the subject will 
continue to be followed until complete resolution or stabilization of the AE with no 
expectation or need for further treatment.  The reason(s) for failure to place the implant will 
be documented on the Procedure CRF. 
 
 

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8.0 
STUDY METHODS 
The study assessments, beginning with the baseline assessments used for screening potential 
study participants, are described below by visit. 
8.1 
MEDICAL THERAPY REGIMEN – ALL SUBJECTS 
All participants in the study will be on a minimum of three (3) anti-hypertensive drugs such 
as, but not limited to, the following: 
Diuretics 
Class 
Generic name 
Brand name 
Side effects 
Thiazide diuretics 
chlorothiazide 
Diuril 
Weakness, confusion, potassium 
depletion, gout, fatigue, thirst, frequent 
urination, lightheadedness, muscle 
cramps, diarrhea or constipation, 
increased sensitivity to sunlight, 
allergic reaction in people allergic to 
sulfa drugs, impotence. 
chlorthalidone 
Hygroton 
hydrochlorothiazide 
Esidrix, 
HydroDiuril, 
Microzide 
indapamide 
Lozol 
metolazone 
Mykrox, 
Zaroxolyn 
Loop diuretics 
bumetanide 
Bumex 
Weakness, confusion, potassium 
depletion, gout, fatigue, thirst, diarrhea 
or constipation, increased sensitivity to 
sunlight, allergic reaction in people 
allergic to sulfa drugs, impotence. 
ethacrynic acid 
Edecrin 
furosemide 
Lasix 
torsemide 
Demadex 
Potassium-sparing 
diuretics/ 
aldosterone-receptor 
blockers* 
amiloride 
Midamor 
Excessive potassium levels, especially 
in patients with kidney disease; breast 
enlargement and erectile dysfunction in 
men; menstrual irregularities in 
women. 
spironolactone 
Aldactone 
triamterene 
Dyrenium 
eplerenone 
Inspra 
Headache, dizziness, diarrhea, fatigue, 
upset stomach, and breast enlargement 
or tenderness. 
*Note: Potassium-sparing diuretics also directly or indirectly block aldosterone, a hormone that raises blood 
pressure by causing the kidneys to conserve sodium and water. As a result, these four medications are sometimes 
also known as aldosterone-receptor blockers. Amiloride (Midamor), spironolactone (Aldactone), and triamterene 
(Dyrenium) also affect other hormones and thus carry some unwanted side effects, such as breast enlargement and 
impotence in men and menstrual irregularities in women. Eplerenone (Inspra) is the only one of these medications 
that affects solely aldosterone and not other hormones. 
 
 

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Anti-adrenergic drugs 
Class 
Generic 
name 
 Brand 
name 
Side effects 
Beta blockers 
(cardioselective) 
atenolol 
Tenormin 
Wheezing, dizziness, depression, impotence, fatigue, 
insomnia, decreased HDL cholesterol levels, lower exercise 
tolerance. Can worsen peripheral vascular disease and heart 
failure. Abrupt withdrawal may trigger angina or a heart 
attack in patients with heart disease. 
metoprolol 
Lopressor 
metoprolol 
extended 
release 
Toprol-XL 
nebivolol 
Bystolic 
Beta blockers 
(nonselective) 
nadolol 
Corgard 
pindolol 
Visken 
propranolol 
Inderal, 
Inderal LA 
sotalol 
Betapace 
timolol 
Blocadren 
Alpha-1 blockers 
doxazosin 
Cardura 
A drop in blood pressure upon standing up, fainting, 
weakness, heart palpitations, headache, nasal congestion, dry 
mouth. 
prazosin 
Minipress 
terazosin 
Hytrin 
Alpha and beta 
blockers 
carvedilol 
Coreg 
Wheezing, depression, insomnia, diarrhea, lightheadedness, 
dizziness, unusual tiredness or weakness, drying of the eyes, 
erectile dysfunction, headache, dry mouth, nasal congestion, 
decreased HDL cholesterol levels, lower exercise tolerance, 
a drop in blood pressure upon standing up, fainting, heart 
palpitations. Can worsen peripheral vascular disease and 
heart failure. Abrupt withdrawal may trigger angina or a 
heart attack in patients with heart disease. 
labetalol 
Normodyne, 
Trandate 
Peripheral nerve–
acting agents 
guanethidine 
Ismelin 
A drop in blood pressure upon standing up, depression, nasal 
stuffiness, nightmares. Guanethidine may slow heart rate and 
reserpine may cause indigestion. 
reserpine 
Serpalan 
 
 

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Direct-acting vasodilators 
Generic 
name 
Brand name 
Side effects 
hydralazine 
Apresoline 
Headaches, palpitations, weakness, flushing, nausea. Minoxidil may cause hair 
growth, fluid retention, and increased blood sugar. 
minoxidil 
Loniten 
Calcium-channel blockers 
Generic 
name 
Brand name 
Side effects 
amlodipine 
Norvasc 
Headache, dizziness, edema, and heartburn. Nifedipine can cause palpitations. 
Diltiazem and verapamil can cause constipation and a slowed heartbeat. 
diltiazem 
Cardizem, 
Dilacor, others 
felodipine 
Plendil 
isradipine 
DynaCirc 
nicardipine 
Cardene, 
Cardene SR 
nifedipine 
Adalat CC, 
Procardia XL 
verapamil 
Calan, Isoptin, 
others 
ACE inhibitors 
Generic 
name 
Brand name 
Side effects 
benazepril 
Lotensin 
Cough, rash, fluid retention, high potassium levels, and loss of taste. May cause 
low blood pressure and fainting. Can worsen kidney impairment if narrowed 
arteries feed both kidneys. May cause fetal abnormalities. 
captopril 
Capoten 
enalapril 
Vasotec 
fosinopril 
Monopril 
lisinopril 
Prinivil, Zestril 
quinapril 
Accupril 
ramipril 
Altace 
 
 

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Angiotensin-receptor blockers (ARB) 
Generic name 
Brand name 
Side effects 
candesartan 
Atacand 
Muscle cramps, dizziness. 
eprosartan 
Teveten 
irbesartan 
Avapro 
losartan 
Cozaar 
olmesartan 
Benicar 
telmisartan 
Micardis 
valsartan 
Diovan 
 
Combination antihypertensive drugs 
Class 
Generic name 
Brand name 
Potassium-sparing and 
thiazide diuretics 
amiloride + HCTZ* 
Moduretic 
spironolactone + HCTZ 
Aldactazide, Spironazide, Spirozide 
triamterene + HCTZ 
Dyazide, Maxzide 
Alpha blocker and 
diuretic 
prazosin + polythiazide 
Minizide 
Beta blocker and 
diuretic 
atenolol + 
chlorthalidone 
Tenoretic 
bisoprolol + HCTZ 
Ziac 
metoprolol + HCTZ 
Lopressor HCT 
nadolol + 
bendroflumethiazide 
Corzide 
propranolol + HCTZ 
Inderide, Inderide LA 
timolol + HCTZ 
Timolide 
ACE inhibitor and 
diuretic 
benazepril +HCTZ 
Lotensin HCT 
captopril + HCTZ 
Capozide 
enalapril + HCTZ 
Vaseretic 
fosinopril + HCTZ 
Monopril HCT 

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Class 
Generic name 
Brand name 
ACE inhibitor and 
diuretic (continued) 
lisinopril + HCTZ 
Prinzide, Zestoretic 
moexipril + HCTZ 
Uniretic 
quinapril + HCTZ 
Accuretic 
ARB and diuretic 
candesartan + HCTZ 
Atacand HCT 
eprosartan + HCTZ 
Teveten HCT 
irbesartan + HCTZ 
Avalide 
losartan + HCTZ 
Hyzaar 
telmisartan + HCTZ 
Micardis HCT 
valsartan + HCTZ 
Diovan HCT 
Calcium-channel 
blocker and ACE 
inhibitor 
amlodipine + 
benazepril 
Lotrel 
diltiazem + enalapril 
Teczem 
felodipine + enalapril 
Lexxel 
verapamil + 
trandolapril 
Tarka 
Other combinations 
methyldopa + HCTZ 
Aldoril 
reserpine + 
chlorothiazide 
Diupres 
reserpine + HCTZ 
Hydropres 
aliskiren + HCTZ 
Tekturna HCT 
Calcium-channel 
blocker and ARB 
amlodipine + valsartan 
Exforge 
amlodipine + 
olmesartan 
Azor 
*HCTZ=hydrochlorothiazide 
Medications for treating hypertension 
http://www.health.harvard.edu/newsletters/Harvard_Womens_Health_Watch/2009/August/Medications-for-treating-hypertension 
(downloaded on 7/3/2012) 
 
All subjects that are implanted with the MobiusHD will be required to be on duel antiplatelet 
therapy (ie. aspirin 81-325 mg daily and clopidogrel 75 mg daily; substitutes can be used but 
should be equivalent) for three (3) days prior to the implant procedure as well as three (3) 
months post-procedure.  Aspirin will continue for the duration of study. 

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Management of subject’s individual risk factors as appropriate, e.g., statins, smoking 
cessation, nutritionist, diabetes management, etc., will remain as standard of care and any 
changes to this regimen will be documented by the study team. 
Subjects should be advised of the importance of not stopping their medical therapy regimen 
before first consulting with the study center.  In the absence of changes initiated by the study 
physician in response to severe symptomatic drops in blood pressure, subjects should not 
reduce or stop their anti-hypertensive medication dosage until the 6-month time point, at 
which time the Principle Investigator may decide to reduce medication use. 
8.2 
STUDY ENROLLMENT 
The number of subjects to be enrolled in the study is up to 20.  This sample size is estimated 
to be sufficient to yield acceptable, first-in-man, safety and effectiveness data for initial 
analysis and to support future regulatory submissions.  It is anticipated that up to ten (10) 
centers inside the United States will be needed to enroll this study in a timely fashion.  Each 
investigational site will be expected to enroll at least two (2) and up to eight (8) subjects. 
8.3 
INVESTIGATOR QUALIFICATION AND TRAINING 
The MobiusHD system should only be used by interventionists with expertise in the 
navigation of catheter systems and stenting procedures.  Qualified potential Investigators for 
this clinical trial will have successfully placed carotid stents in at least 10 patients in the 12 
months prior to Site Initiation and 100 carotid stents during their careers.   
Qualified study centers will be expected to work in research teams that include the 
appropriate specialties for the proper conduct of the study (e.g., interventional 
cardiologist(s) or neurointerventionalist(s) experienced in carotid stenting, internists, and 
study coordinator(s)).  Qualified interventionists will have successfully performed carotid 
stenting in at least 10 patients in the last calendar year and 100 patients in their careers. 
All Investigators and those to whom the Investigator delegates study responsibilities (see 
Investigator Agreement), will be trained on the Protocol by a representative of the Sponsor.  
Interventional Investigators using the investigational device will be trained on the 
Instructions For Use of the MobiusHD system.  Additional training such as preparation and 
table-top deployment of a demonstration device, animal lab, and/or case support will be 
offered by Sponsor, as appropriate, to meet the needs of the site Investigators.  In addition, 
training on topics such as Medical Imaging Guidelines (“Core Lab”, Appendix I), internet-
based CRF (iCRF) data entry procedures, and investigational device inventory management 
will be conducted at Investigator meetings and during site visits.  All training completed will 
be appropriately documented.  Research staff responsible for assessing neurological status 
using the NIHSS must be certified in the proper administration of this assessment tool.  
Training and Certification on administration of the NIHSS, if such documentation is not 
already available, can be obtained by taking a web-based accredited course such as: 
http://nihss-english.trainingcampus.net/uas/modules/trees/windex.aspx  
 
 

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8.4 
SELECTION AND SCREENING OF SUBJECTS 
Prior to subject participation in this study, the study team must obtain written IRB/EC 
approval for the Protocol and the ICF.  The study population for this clinical trial will be 
comprised of adult patients who have been diagnosed with stage 2 resistant hypertension.  In 
addition, these patients must satisfy the inclusion and exclusion criteria.  The trial will 
prospectively enroll up to 20 subjects.  Patients presenting with stage 2 resistant 
hypertension must be on a minimum of three (3) anti-hypertensive medications.  Clinical 
site personnel will review the patient’s medical history for eligibility.  Potential candidates 
will be fully informed by a member of the research team as to the purpose of the study and 
the nature of the implantation procedure.  The implantation procedure will be described and 
its potential risks and benefits will be explained in detail.  Patients who voluntarily agree to 
participate in the trial will be asked to sign and date the written Informed Consent Form 
(ICF).  If approved by the reviewing IRB/EC, subjects may indicate verbal, witnessed 
consent with the signature of a patient representative not associated with the study team if 
cognition is intact but the subject is unable to sign (e.g., the subject has inhibited hand 
function or visual disturbance).  
The approved ICF must be signed for study enrollment prior to performing study related 
assessments.  A copy of the signed and dated ICF should be provided to the subject.  
Subjects must be informed that they may withdraw from the study at any time, and for any 
reason, and will continue to receive therapy as indicated by their physician.  Internet-based 
Case Report Forms must be completed for each subject who consents to study participation.   
8.5 
BASELINE ASSESSMENT: VISIT 1 (DAY 0-14) – ASSESSED DAY 14 
The following information will be assessed and the documentation will be maintained as 
source records at the study site: 
 Medical history; 
 Office cuff blood pressure (Note: Office cuff BP recordings must be performed as 
detailed in Appendix IV); 
 Check for orthostatic blood pressure and orthostatic pulse assessments; 
 Daily patient diary assessments of blood pressure and medication compliance; 
 Assessment for renal artery stenosis.  If duplex, renal MRA, renal angiography or 
renal CTA has been performed in the 12 months preceding screening, and in the 
absence of evidence of renal artery stenosis, no further work-up is needed. 
Otherwise, an abdominal angiogram in the 20-degree LAO projection will be 
performed prior to device placement.; 
 Current medication history including all hypertensive medication; 
 Physical examination; 
 NIH Stroke Scale (NIHSS); and 
 Laboratory testing, including hemoglobin (Hg), platelet count (Plt), prothrombin 
time (PT), partial thromboplastin time (PTT), international normalized ratio (INR), 
high-density lipoprotein (HDL), low-density lipoprotein (LDL-C), creatinine (Cr), 
glucose, and pregnancy test (if subject is a female with child-bearing potential).   

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Local laboratories with appropriate certifications will be used for all laboratory 
testing. 
 12 lead electrocardiogram. 
To avoid repeat testing, any of the testing listed above, performed within 90 days prior to 
presentation for the initial baseline assessment, may be used as baseline data. 
8.6 
BASELINE ASSESSMENT: VISIT 2 (DAY 15-30) – (+45 DAYS) 
 Assessment of patient diary; 
 Office cuff blood pressure (Note: Office cuff BP recordings must be performed as 
detailed in Appendix IV); 
 Check for orthostatic blood pressure and orthostatic pulse assessments; 
 Changes of medication regimen; 
 Review and assessment of adverse events; 
 CTA scan or MRA to assess exclusion criteria, from root of Aortic artery to 
intracranial vessels; 
 Duplex imaging of the carotid artery; 
 Assessment for carotid hypersensitivity; 
 24 hour ambulatory blood pressure measurement (24hr ABPM); and  
8.7 
BASELINE ASSESSMENTS VISIT 3 (DAY OF PROCEDURE) – ASSESSED ON DAY OF 
PROCEDURE 
 Physical examination; 
 Assessment of patient diary; 
 Changes of medication regimen; 
 Review and assessment of adverse events; 
 Office cuff blood pressure (Note: Office cuff BP recordings must be performed as 
detailed in Appendix IV); 
 Digital subtraction angiography – Inclusion/Exclusion criteria; 
 Assessment of all Inclusion/Exclusion criteria; and 
 Implantation of MobiusHD. 
8.8 
BASELINE ANGIOGRAM  
After consent, all subjects should complete the baseline assessments outlined in  
Sections 8.5 – 8.7 and the Schedule of Study Visits and Assessments (Table 7).  Subjects 
who meet all Inclusion/Exclusion criteria should then undergo angiogram according to 
imaging guidelines to measure and check the remaining Inclusion/Exclusion criteria. If renal 
duplex, renal MRA, renal CTA or renal angiography was performed in the 12 months 
preceding screening and showed no evidence of renal artery stenosis then no further work-
up is needed. If no workup has been done then an abdominal angiogram in the 20 degree 

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LAO projection will be done prior to device implantation. During this angiogram procedure, 
if all Inclusion/Exclusion criteria are met, then the subject may be treated with the 
MobiusHD.  
8.9 
MOBIUSHD PROCEDURE 
Prior to implantation, all assessment data should be entered into the eDC and there should be 
documentation that the patient has taken the dual antiplatelet regimen for the three (3) days. 
Also, diabetic subjects taking drugs containing metformin should be switched to insulin 
management the night before the implant procedure and should not be restarted on 
metformin until 48 hours after the last injection of contrast dye. 
The patient will be placed in the standard supine position on the imaging table and prepped 
and draped as with any standard carotid transcatheter therapeutic or diagnostic study. Use of 
a head-stabilizing device is optional for this study and depends on physician preference. 
Light sedation and local anesthesia is recommended to allow for clinical neurological 
assessment, as needed. 
In patients without adequate pre-procedure work-up for renal artery stenosis, non-selective 
renal angiography should be performed based on local technique preferences.  In the 
absence of a local preference, begin with placement of the pigtail or lateral spray (i.e., tennis 
racket) catheter at the level of L-1. Make certain the catheter is easily movable and can 
rotate to ensure the tip is not inadvertently positioned in a thoracic or lumbar branch. Place 
the image intensifier at 20 degrees left anterior oblique and inject 15 cc/sec for 2 seconds 
under breath-hold conditions with digital subtraction. Different obliquity images may be 
needed if the renal ostia are eclipsed by overlying mesenteric vessels.   
Heparin is given during the angiogram and implantation procedures (100 I.U./kg).  ACT  
> 250 must be documented before implantation and measurement of platelet function is 
recommended according to local carotid stent protocols.   
The aortic arch is defined by baseline angiography in the left anterior oblique projection.  
Selective carotid angiography of the target vessel for implant is performed in orthogonal 
views. If the aortic arch and carotid meet the study inclusion criteria then the operator will 
proceed with the implant.  
The target common carotid is accessed with a 6 Fr kink-resistant sheath or an 8 Fr guiding 
catheter using the external carotid anchor-wire, telescoping technique or whatever approach 
the operator typically uses for carotid stenting.  The guide or sheath tip should be in a stable 
position within the common carotid prior to removal of the .035 or .038 inch wire. 
Once the guiding catheter or sheath is in position and the ACT is above 250 seconds, the 
ICA is accessed with a .014 inch guidewire. The implant delivery catheter is then prepared 
and introduced over the guidewire. Carotid imaging and roadmaps may be useful at this 
time.  Selection of the implant size should be based on the angiographic measurements of 
the carotid sinus and these should coincide with the non-invasive (Duplex and or CTA) 
measurements. To select an appropriate implant size, select the size that correlates to the 
measurement made of the diameter of the carotid sinus.   

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Some degree of distal embolization likely occurs during all transcatheter interventional 
procedures. The clinical sequela is defined by the sensitivity of the target organ to segmental 
ischemia and the burden of embolic load.14 Due to the low burden of embolic load expected 
in this procedure due to the inclusion and exclusion criteria the use of a protection device is 
based on operator preference. Distal protection may be used with any FDA-approved distal 
protection device but is not mandatory. Precise placement of the implant within the sinus is 
required and should be controlled by road map or contrast injections.  Gentle forward and 
backward movements may be needed as with a carotid stent, to release tension and eliminate 
redundancy within the delivery catheter.  Implant delivery is performed by very slow 
retraction of the implant delivery catheter sheath and this is performed by releasing the 
initial lock, then sliding the control knob proximally. The device will flower open and 
during this maneuver movement of the delivery catheter must be strictly avoided. The 
operator has the opportunity to re-sheath and reposition or release the second lock and 
deploy the implant, depending on his or her satisfaction with the implant position and 
apposition. Following implantation, the delivery catheter is removed; fluoroscopic guidance 
should be used until the nosecone is retracted past the implant.  Post procedure angiography 
should be performed to evaluate proper implant positioning, apposition, and maintenance of 
the vessel lumen. Completion angiograms should display the implanted site and the 
dependent territory in at least two (2) orthogonal planes.    
Refer to the IFU (Appendix VI) for detailed preparation procedures and detailed sizing and 
placement of the device. 
8.10 
POST-PROCEDURE CARE 
Following the angiogram and procedure, the subjects will be asked to lie flat with a  
pressure bandage over the groin puncture site according to the local standard of care (e.g., 
assess for bleeding, hematoma, pedal pulses).  A post-implant carotid duplex imaging study 
is required prior to discharge.  The subject will be monitored closely for significant change 
in status (peri-procedural adverse events).   
Implanted subjects should be monitored in an intensive care or intermediate care unit; with 
emphasis on meticulous blood pressure monitoring over the first 12 hours for recognition 
and/or prevention of severe hypotension (symptomatic drop in BP bellow 90/50) or severe 
hypertension (rise in BP above 180/100 mmHg with or without symptoms).  If blood 
pressure drops below 90/50 with clinical symptoms or the subject has symptoms with a 
relative drop from baseline pressure due to past compensatory changes, then aggressive 
rescue (may include pressors, fluids, placement in trendelenburg position, withdrawal of 
blood pressure medications, etc.) should be provided to increase blood pressure to a point 
where the symptoms are alleviated.  Blood pressure medications can be withdrawn if there is 
an abrupt drop in blood pressure from baseline, and should be documented as an adverse 
event and logged in the medication log.  Aggressive use of protamine sulfate to antagonize 
the total dose of heparin should be avoided due to risk of implant thrombosis.  Take vital 
signs once an hour for three (3) hours and enter data in the post-procedure iCRF.  Standard 
post-procedure labs should be taken prior to discharge.  These labs should include CBC, 
Chem 7, and Hematologic labs.   

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Prior to release from the hospital the subject’s lying and standing bedside blood pressure 
should be measured and analyzed for orthostatic changes.  In addition, the subject must be 
ambulatory, without dizziness or other symptoms. 
If a new neurological deficit or a significant change in neurological status is determined 
using the NIHSS during post-procedure monitoring, assess for intracranial thrombus or 
hemorrhage using CT scan or MRI, if deemed appropriate by the Investigator under standard 
of care, and treat accordingly. 
Body temperature >38˚C should be investigated, and testing performed per the standard of 
medical care (e.g., blood cultures, urinalysis, chest X-ray, phlebitis source), to allow 
appropriate treatment to be implemented.  
8.11 
SUBJECT DISCHARGE  
On the day of discharge, clinical and neurological assessment of the subject is completed.  
Duplex imaging is done to visualize the carotid sinus and to assess for complications. Office 
cuff blood pressure should be taken and documented on the discharge iCRF.  Orthostatic 
blood pressure measurement and orthostatic pulse assessments should be taken (sitting and 
standing).  Assessment for any new or unresolved adverse events will be made and any 
changes in medication regimen will be recorded. 
8.12 
7-DAY FOLLOW-UP VISIT (+2 / -3 DAYS) 
During the 7-Day follow-up visit, clinical assessment of the subject and evaluation of 
neurological symptoms will be performed by the study team.  Office cuff blood pressure will 
be taken and assessment of the subject diary will be reviewed.  A six minute walk test will 
be done following the March 2002 ATS Statement: Guidelines for the Six-Minute Walk 
Test, and orthostatic assessment should be done following this test.   Orthostatic blood 
pressure measurement and orthostatic pulse assessments should be taken (sitting and 
standing).  The neurological examinations are classified by NIHSS.  Duplex imaging is done 
to visual carotid sinus and to assess for complications.  Assessment for any new or 
unresolved adverse events will be made and any changes in medication regimen will be 
recorded. 
8.13 
30-DAY FOLLOW-UP VISIT (+7 / -7 DAYS) 
During the 30-Day follow-up visit, clinical assessment of the subject and evaluation of 
neurological symptoms will be performed by the study team.  Duplex imaging is done to 
visualize the carotid sinus and to assess for complications. Office cuff blood pressure will be 
taken and assessment of the subject diary will be reviewed.  A six minute walk test will be 
done following the March 2002 ATS Statement: Guidelines for the Six-Minute Walk Test 
and orthostatic assessment should be done following this test.  Orthostatic blood pressure 
measurement and orthostatic pulse assessments should be taken (sitting and standing).  The 
neurological examinations are classified by NIHSS.  Assessment for any new or unresolved 
adverse events will be made and any changes in medication regimen will be recorded. 
8.14 
90-DAY FOLLOW-UP VISIT (+14 / -14 DAYS) 
During the 90-Day follow-up visit, clinical assessment of the subject and evaluation of 
neurological symptoms will be performed by the study team.  Office cuff blood pressure will 

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be taken and assessment of the subject diary will be reviewed.   
24-hour ambulatory blood pressure monitoring will be assessed.  The neurological 
examinations are classified by NIHSS.  Assessment for any new or unresolved adverse 
events will be made and any changes in medication regimen will be recorded. 
8.15 
180-DAY FOLLOW-UP VISIT (+14 / -14 DAYS) 
During the 180-Day follow-up visit, clinical assessment of the subject and evaluation of 
neurological symptoms will be performed by the study team.  Office cuff blood pressure will 
be taken and assessment of the subject diary will be reviewed.  24-hour ambulatory blood 
pressure monitoring will be assessed.  The neurological examinations are classified by 
NIHSS.  Duplex imaging is done to visualize the sinus and to assess for complications. 
Assess for any new or unresolved adverse events and record any changes in medication 
regimen. Assessment for any new or unresolved adverse events will be made and any 
changes in medication regimen will be recorded. 
8.16 
365-DAY FOLLOW-UP VISIT (+14 / -14 DAYS) 
During the 365-Day follow-up visit, clinical assessment of the subject and evaluation of 
neurological symptoms will be performed by the study team.  Office cuff blood pressure will 
be taken.  The neurological examinations are classified by NIHSS.  Assessment for any new 
or unresolved adverse events will be made and any changes in medication regimen will be 
recorded. 
8.17 
LONG TERM FOLLOW-UP VISITS - 18, 24, 30, AND 36-MONTH FOLLOW-UP VISIT 
(+14 / -14 DAYS) 
During the long term follow-up visits after the angiogram/implantation procedure, clinical 
assessment of the subject and evaluation of neurological symptoms will be performed by the 
study team.  Office cuff blood pressure will be taken.  The neurological examinations are 
classified by NIHSS.  Assessment for any new or unresolved adverse events will be made 
and any changes in medication regimen will be recorded. 
8.18 
UNSCHEDULED FOLLOW-UP VISIT 
If an unscheduled follow-up visit is required, the study subject should be assessed for new or 
unresolved adverse events.  Any testing required, including imaging studies, should be 
provided to the study Sponsor for DSMB adjudication.  Office cuff blood pressure will be 
taken and assessment of the subject diary will be reviewed. Change of medications, 
diagnostic test results, or interventions should be documented. 
8.19 
SCHEDULE OF STUDY VISITS AND ASSESSMENTS 
A summary of the study related assessments as outlined above is described in Table 7. 
 
 
 

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TABLE 7: SCHEDULE OF STUDY VISITS AND ASSESSMENTS 
 
Follow-up 
Long Term 
Follow-up 
Visit 
Visit 1 
Visit 2 
Visit 3/ 
Procedure 
Discharge 
7 Days (+2/-3 
days) 
30 Days (+/- 7 
days) 
90 Days (+/- 14 
days) 
180 Days (+/- 14 
days) 
365 Days (+/- 14 
days) 
18,  24, 30 and 
36 Months 
(+/- 14 days) 
Eligibility 
 
 
 
 
 
 
 
 
 
 
Informed 
Consent 
 
 
 
 
 
 
 
 
 
 
Medical History  
 
 
 
 
 
 
 
 
 
 
Physical  
 
 
 
 
 
 
 
 
 
 
Neurological 
Exam 
 
 
 
 
 
 
 
 
 
 
Concomitant 
medications 
 
 
 
 
 
 
 
 
 
 
Baseline 12 lead 
ECG 
 
 
 
 
 
 
 
 
 
 
Blood Testing 
 
 
 
 
 
 
 
 
 
 
Patient Diary 
 
 
 
 
 
 
 
 
 
 
Duplex Imaging 
 
 
 
 
 
 
 
 
 
 
CT or MR 
Angiography 
 
 
 
 
 
 
 
 
 
 
Renal Artery 
CTA/MRA or 
Duplex* 
 
 
 
 
 
 
 
 
 
 
24 hour ABPM 
 
 
 
 
 
 
 
 
 
 
Assessment for 
Carotid 
 
 
 
 
 
 
 
 
 
 
6MWT 
 
 
 
 
 
 
 
 
 
 
MobiusHD 
Placement 
 
 
 
 
 
 
 
 
 
 
Office cuff BP 
Measurement 
 
 
 
 
 
 
 
 
 
 
Discharge  
 
 
 
 
 
 
 
 
 
 
Adverse Events 
 
 
 
 
 
 
 
 
 
 
* If not performed in the 12 months preceding screening 
9.0 
STUDY COMPLETION 
After the subject has completed the 3-Year follow-up visit, a Subject Termination iCRF 
must be completed.  During the course of the study, it is possible that subjects will be 
withdrawn from the study early.  Factors leading to subject withdrawal may include, but are 
not limited to, the following: 

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 Subject Withdrawal - A subject may voluntarily withdraw from the study at any 
time without affecting his or her future medical treatment or benefits.  In addition, 
the Investigator may withdraw a subject from the study if the subject refuses 
further testing or follow-up evaluations, or for any other reason as determined by 
the Investigator.   
 Subject Lost to Follow-Up – If the Investigator has attempted to contact a subject 
at least three (3) times and receives no response, the subject may be lost to follow-
up.  The research staff should document at minimum three (3) attempts to contact 
the subject prior to terminating the subject from the trial.   
 Subject Death - When a subject expires, the Serious Adverse Event and Subject 
Termination iCRFs must be completed promptly.  Source documents such as death 
summary, autopsy report (if done), and a copy of the death certificate should be 
redacted of personal identifiers and provided to the designated clinical monitor and 
DSMB to describe the cause of the subject’s death.  The Investigator will notify the 
IRB/EC and Sponsor within 24 hours of learning of the event. 
The Termination iCRF should be completed for each study subject, to record date and 
reason for early termination (if subject does not complete the study) or at the final visit (if 
subject completes all study time points). 
10.0 
CONCOMITANT MEDICATIONS 
To be eligible for enrollment, study participants must require a minimum of three (3) anti-
hypertensive medications at the time of entry into the study.  Additionally, all subjects will 
remain on at least three (3) anti-hypertensive medications for the duration of the study. 
In addition to the required regimen of hypertensive medications, all study subjects will be 
required to adhere to a regimen of duel antiplatelet therapy consisting of aspirin (81-325 mg 
daily) and clopidogrel (75 mg daily), or equivalent medications.  If alternative equivalent 
medications are used, these should be initiated at least three (3) days prior to the implant 
procedure and continued for at least three (3) months post-procedure.  Use of aspirin is 
required for the duration of study. 
Appropriate management of subject’s individual risk factors such as statins, smoking 
cessation, nutrition, diabetes will remain as standard of care and any changes to this regimen 
will be documented by the study team. 
Subjects should be advised of the importance of continuing their medical therapy regimen 
without consulting with the study center.  Subjects should not reduce or stop their anti-
hypertensive medication dosage until the 6-month time point, at which time the Principle 
Investigator may decide to reduce medication as per the site’s protocol. 
All medications will be recorded on the Concomitant Medication log.   
 
 
 

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11.0 ADVERSE EVENTS 
Safety assessments include adverse events and serious adverse events.  The reporting period 
is from the initial treatment through the last study visit (Month 36). 
11.1 
DEFINITIONS OF ADVERSE EVENTS 
An adverse event is any untoward and unintended sign, symptom or disease temporally 
associated with the use of an investigational device/drug/biologic or other protocol-imposed 
intervention, regardless of the suspected cause. Conditions or diseases that are chronic but 
stable should not be recorded on AE pages of the CRF.  Changes in a chronic condition of 
disease that are consistent with natural disease progression are NOT adverse events and also 
should not be recorded on the AE pages of the CRF.   
11.1.1 Serious Adverse Events (SAE) 
An AE should be classified as an SAE and reported as such, if it meets one or more of the 
following criteria: 
 It results in death (i.e., the AE actually causes or leads to death) 
 It is life threatening (i.e., the AE places the subject at immediate risk of death) 
 It requires or prolongs inpatient hospitalization 
 It results in persistent or significant disability/incapacity (i.e., the AE results in 
substantial disruption of the subject’s ability to conduct normal life functions) 
 It results in a congenital anomaly/birth defect in a neonate/infant born to a 
mother exposed to the investigational product 
 It is considered a significant medical event by the investigator based on medical 
judgment (e.g., may jeopardize the subject or may require medical/surgical 
intervention to prevent one of the outcomes listed above). 
If a subject is hospitalized to undergo a medical or surgical procedure as a result of an AE, 
the event responsible for the procedure, not the procedure itself, should be recorded as the 
event. For example, if a subject is hospitalized to undergo coronary bypass surgery, record 
the heart condition that necessitated the bypass. 
 
Hospitalizations for the following reasons will not be recorded as SAEs: 
 Hospitalization or prolonged hospitalization for diagnostic or elective surgical 
procedures for preexisting conditions 
 Hospitalization or prolonged hospitalization required to allow outcome 
measurement for the study 
 Hospitalization or prolonged hospitalization for scheduled therapy of the target 
disease of the study. 
 
 
 

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11.1.2 Unanticipated Adverse Device Effects (UADE) (where applicable) 
An unanticipated adverse device effect (UADE) is any serious adverse effect on health or 
safety or any life-threatening problem or death caused by or associated with a device, if that 
effect, problem, or death was not previously identified in nature, severity or degree of 
incidence. Anticipated adverse events are identified in Section 11.3.   
11.2 
ADVERSE EVENT ASSESSMENT AND DOCUMENTATION 
All subjects who have been exposed to the study treatment will be evaluated for adverse 
events. All adverse events, regardless of severity and whether or not they are ascribed to the 
study treatment, will be recorded in the source documents and CRF using standard medical 
terminology.  
All adverse events will be evaluated beginning with onset, and evaluation will continue until 
resolution is noted, or until the investigator determines that the subject’s condition is stable. 
The investigator will take appropriate and necessary therapeutic measures required for 
resolution of the adverse event. Any medication necessary for the treatment of an adverse 
event must be recorded on the concomitant medication case report form.  
All AEs will be characterized by the following criteria: 
 Event term 
 Intensity or severity 
 Expectedness 
 Relationship to study treatment 
 Outcome 
 Treatment or action taken. 
 
Whenever possible, recognized medical terms should be used when recording AEs. 
Colloquialisms and/or abbreviations should not be used. Only one medical concept, preferably 
a diagnosis instead of individual symptoms, should be recorded as the event. 
 
If more than one distinct adverse event occurs, each event should be recorded separately. 
However, if known at the time of reporting, a diagnosis (i.e., disease or syndrome) should be 
recorded on the CRF rather than individual signs and symptoms (e.g., record congestive 
heart failure rather than dyspnea, rales, and cyanosis). However, if a constellation of signs 
and/or symptoms cannot be medically characterized as a single diagnosis or syndrome at the 
time of reporting, each individual event should be recorded as a separate AE. A diagnosis 
that is subsequently established should be reported as follow-up information. However, 
signs and symptoms that are considered unrelated to an encountered syndrome or disease 
should be recorded as individual AEs (e.g., if congestive heart failure and severe headache 
are observed at the same time, each event should be recorded as an individual AE). 
 
 
 

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Adverse events occurring secondary to other events (e.g., sequelae) should be identified by 
the primary cause; a "primary" event, if clearly identifiable, should represent the most 
accurate clinical term to record as the AE event term.  For example: 
 
Orthostatic hypotension fainting and fall to floorhead traumaneck pain 
 
The primary event is orthostatic hypotension and the sequelae are head trauma and neck 
pain. 
 
11.2.1 Classification of Adverse Events by Intensity/Severity 
All adverse events should be graded on a four-point scale (mild, moderate, marked, severe) 
for intensity/severity. These definitions are as follows: 
 
Mild:  
Transient discomfort; no medical intervention/therapy required and 
does not interfere with daily activities. 
Moderate:  
Low level of discomfort or concern with mild to moderate limitation 
in daily activities; some assistance may be needed; minimal or no 
medical intervention/therapy required. 
Marked:  
Considerable discomfort with limitation in daily activities, some 
assistance usually required; medical intervention/therapy usually 
required. 
Severe:  
Extreme discomfort and limitation in daily activities, significant 
assistance required; significant medical intervention/therapy required. 
 
There is a distinction between the severity and the seriousness of an adverse event. Severity 
is a measurement of intensity; thus, a severe reaction is not necessarily a serious adverse 
event (SAE). For example, a headache may be severe in intensity, but would not be serious 
unless it met one of the criteria for serious adverse events. 
 
11.2.2 
Expectedness 
All AEs will be evaluated as to whether they are expected or unexpected. 
  
Expected (anticipated): 
An adverse event is expected when the nature, 
severity, or degree of incidence was previously 
described.   
 
Unexpected (unanticipated): 
An adverse event is unexpected when the nature, 
severity, or degree of incidence was not previously 
described.  
 
 
 

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11.2.3  Relatedness  
The study investigator will evaluate if the AE is related to the MobiusHD system. 
Relationship is defined in the following manner: 
  
Not related: Evidence indicates no plausible direct relationship to the study device, 
such that: 
 A clinically plausible temporal sequence is inconsistent with the onset of the AE 
and device administration; and/or 
 A causal relationship is considered biologically implausible 
 The AE can be attributed to concurrent/underlying illness, other drugs, or 
procedures. 
  
Related: Evidence indicates a reasonable temporal sequence of the event with the 
study device administration exists, or that the association of the event with study 
device administration is unknown and the event is not reasonably supported by other 
conditions, such that: 
 There is a clinically plausible time sequence between onset of the AE and study 
treatment administration; and/or 
 There is a biologically plausible mechanism for study treatment causing or 
contributing to the AE; and 
 The AE cannot be reasonably attributed to concurrent/underlying illness, other drugs, 
or procedures. 
11.2.4 Outcome 
The clinical outcome of an AE will be characterized as follows: 
 
Resolved without sequelae 
 
Resolved with sequelae (specify) 
 
Ongoing (i.e. continuing at time of study discontinuation) 
 
Death. 
11.2.5 Treatment or Action Taken 
 None 
 Medical Intervention 
 Surgical Intervention 
 Other. 
11.3 
ANTICIPATED ADVERSE EVENTS 
Adverse events that are anticipated to occur during the study are listed below. 
 Death; 
 stroke/CVA, TIA or seizure; 
 vessel damage, dissection, occlusion, aneurysm, perforation, Post-Procedure 
neck pain, guidewire perforation, rupture or injury; 

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 damage to, fracture, fragmentation, or dislocation of the implanted device; 
 embolization of air, thrombus, or other embolic debris; 
 end organ ischemia, vessel thrombosis, or spasm; 
 hypotension/hypertension (acute/subacute to 30 days); 
 hypotension/hypertension (chronic>30 days); 
 hypertension recurrent; 
 infection (local or systemic); 
 myocardial infarction; 
 puncture site complications (i.e. vessel occlusion, hemorrhage; hematoma, 
pseudoaneurysm or arteriovenous fistula, excessive blood loss); 
 renal insufficiency, kidney failure, hematuria; 
 bleeding complications; 
 bradycardia or arrhythmias including ventricular fibrillation of tachycardia; 
 unintentional detachment or implantation of a component of the system, 
inappropriate sizing of the device; 
 drug reaction; 
 allergic reaction to contrast media, medications or device materials; and  
 emergent surgery. 
11.4 
SERIOUS ADVERSE EVENT AND UNANTICIPATED ADVERSE DEVICE EFFECT 
REPORTING 
Serious Adverse Events (SAE) and unanticipated adverse device effects (UADE) must be 
reported to the study sponsor as soon as possible and no later than 2 days after the 
investigator first learns of the event.   
 
For initial reports, investigators should record all case details that can be gathered within the 
reporting timeframe.  The contact information for Vascular Dynamics Inc. is below: 
 
VASCULAR DYNAMICS, INC. 
2134 OLD MIDDLEFIELD WAY 
SUITE J 
MOUNTAIN VIEW, CALIFORNIA   94043 
Phone: (650) 963-9370 
Fax: (650) 963-9029 
clinical@vasculardynamics.com 
 
Relevant follow-up information should be submitted to Vascular Dynamics, Inc. as soon as 
it becomes available and/or upon request. For some events, the sponsor or its designee or the 
medical monitor may follow up with the site by telephone, fax, electronic mail, and/or a 
monitoring visit to obtain additional case details deemed necessary to appropriately evaluate 
the event (e.g., hospital discharge summary, consultant report, or autopsy report). Reports 
relating to the subject’s subsequent medical course must be submitted to the study sponsor 

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until the event has subsided or, in case of permanent impairment, until the event stabilizes 
and the overall clinical outcome has been ascertained. 
11.5 
INDEPENDENT ADJUDICATION OF CLINICAL OUTCOME EVENTS BY DSMB 
All SAEs and UADEs will be reviewed and adjudicated by the DSMB.  Clinical event 
summaries and relevant imaging studies will be reviewed by the DSMB, which includes an 
interventional cardiologist, a neurologist, an internist, and a biostatistician.   
12.0 ETHICS AND REGULATORY CONSIDERATIONS 
12.1 
SUBJECT INFORMATION AND CONSENT PROCEDURES 
The Investigator, or designee, will obtain written informed consent from the subject prior to 
performing study assessments.  The subject will be informed that the Sponsor and regulatory 
authorities will have access to personally identifiable information for the purposes of 
monitoring data against source documentation.  However, all data entered in the database, 
filed, and presented by the Sponsor will be in anonymous form. 
The site-customized ICF (see sample ICF provided by Sponsor), must be approved by 
Vascular Dynamics, Inc. and the IRB/EC before use.  Each investigational Site will provide 
Vascular Dynamics, Inc. with a copy of the IRB/EC approved ICF and renewed approvals 
and consents as appropriate for the duration of the study. 
The original, signed and dated ICF should be retained in the subject’s study records, and a 
copy provided to the subject.  The consent completion will be monitored by the Sponsor or 
designee. 
12.2 
IRB/EC APPROVAL 
The Investigator, or designee, is responsible for submitting the clinical protocol and any 
amendments to the IRB/EC for approval prior to any subject being enrolled and for 
obtaining renewals at periods determined by the IRB/EC for the duration of the study.  
13.0 STATISTICAL METHODS 
Since this is a pilot study designed to evaluate the initial safety of the MobiusHD in subjects 
with stage 2 hypertension, no formal hypothesis testing is planned.  Complete data for each 
study subject will be presented in an individual patient profile consisting of all CRF fields 
and a narrative summary.  Additionally, where appropriate, descriptive statistics will be used 
to tabulate and summarize study outcomes.  Background and demographic characteristics 
will be presented.  Continuous variables will be summarized by descriptive statistics (sample 
size, mean and standard deviation, median, minimum and maximum).  Discrete variables 
will be summarized by frequencies and percentages.  Adverse events will be summarized by 
presenting the number and percentage of patients having any adverse event.  Any other 
information collected (such as severity or relationship to study device) will be listed as 
appropriate.  Any statistical tests performed to explore the data will be used only to highlight 
any interesting comparisons that may warrant further consideration. 

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14.0 RECORDS AND REPORTS 
14.1 
RECORDS 
The investigational site will maintain iCRF and source study records for monitoring and 
audit purposes for the latter of: 
 At least two (2) years after study completion 
 At least two (2) years after Sponsor receives approval from the local governing 
regulatory authority 
 For the period required by the local governing authority and reviewing IRB/EC 
Sponsor is to be advised prior to destruction of study records and notified if study records 
are moved to an off-site location for archiving. 
14.2 
REPORTS 
Investigators at participating sites are required to submit reports in conformance with all 
applicable regulations.   
15.0 DATA MANAGEMENT 
All required data for this study will be collected on appropriate source medical records and 
study forms and entered into a secure, 21 CFR Part 11 compliant, web-based database 
(MedNet Solutions, Inc.).   
16.0 MONITORING OF THE STUDY AND QUALITY CONTROL 
16.1 
DSMB 
All SAEs will be evaluated by the DSMB for potential relationship to the investigational 
device or procedure.  All AEs will be evaluated by Sponsor for significance and relevance 
with respect to trends that may represent a previously unknown or unanticipated risk that 
may relate to the investigational device or procedure.   
16.2 
DATA COLLECTION AND MONITORING 
The Research Coordinator will collect and document data in hospital and clinic charts and 
on source document forms prepared for the study.  iCRF data will be entered in anonymous 
form into the secure web-based, password protected database.  Passwords will not be issued 
by the Sponsor until Site Initiation and database training has been conducted for all 
personnel to whom Investigator has delegated data entry responsibilities.  Hardcopy blank 
CRFs may be reproduced as needed and may be used as source documents; these should be 
signed and dated by the person collecting the data.  Completed iCRFs in final form (with 
queries resolved) may be printed and filed in hardcopy for archiving if required by local 
governing authority.  All data will be exported and stored on appropriate electronic media by 
Sponsor and to biostatistician for analysis.   
The Sponsor will designate and train monitors to review iCRF data against source 
documents for completeness and accuracy.  Discrepant data will be queried; the electronic 

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database will maintain audit trails of all queried and corrected data.  The Investigator is 
responsible for data integrity at the site and will review and electronically sign all 
Inclusion/Exclusion, Adverse Event, Deviation, and Terminations iCRFs. 
16.3 
SOURCE DOCUMENTATION 
Regulations require that Investigators maintain information in the study subject’s medical 
records that corroborate data reported in the iCRFs.  In order to comply with these 
regulatory requirements, at a minimum, the following information should be maintained: 
 Sufficient medical history/physical condition of the study subject before 
involvement in the study to verify protocol entry criteria;  
 Dated and signed notes on the day of entry into the study including a statement 
regarding the consent process that was followed; 
 A log that maps the key to subject identity for monitors and auditors showing 
subject name and assigned identification number.  This record will not be collected 
by Sponsor but should be maintained at the study site so that the appropriate 
medical records are compared to study iCRF data; 
 Dated and signed progress notes, procedure reports, assessments, and diagnostic 
results as appropriate to each study subject visit to confirm iCRF data;  
 Investigator / site radiologist assessment of medical imaging; 
 Evaluate clinical significance of abnormal lab results; 
 Records following adverse events reported, results of diagnostic tests ordered, 
treatment given, and clinical outcome at resolution or stabilization;  
 Dictated procedure report; 
 Dictated discharge summary; 
 Notes regarding medications taken during the study; and 
 Study subject’s condition upon completion of, or withdrawal from, the study. 
16.4 
SITE COMPLIANCE / DEVIATIONS 
The clinical site will be monitored routinely for adequate enrollment, timeliness of data 
submission, and compliance with the Investigational Plan and local regulations.  Consistent 
pattern of non-compliance with respect to the above will require a corrective action plan to 
be negotiated with the Investigator.  If corrective actions are not effective in resolving site 
compliance, the Sponsor may withdraw the clinical site from the study.  
Significant deviation from the protocol will be reported to the Sponsor via the Deviation 
iCRF which may be completed by the site or the Sponsor.  The Sponsor will categorize and 
report deviations (e.g., improper informed consent, inappropriate use of investigational 
device, visit outside window, assessment missed).   
In the event that the Investigator identifies a potential subject that meets all but one (1) 
Inclusion/Exclusion criterion and expresses a medical opinion regarding why it is 
appropriate to consider the patient for the study, this documentation may be submitted to the 

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Sponsor for consideration.  If the Sponsor agrees, then a prospective deviation may be 
approved to allow the subject to be enrolled in the study. 
16.5 
MONITORING PLAN 
Study monitoring activities will include Site Initiation Visits, interim Site Monitoring Visits 
and a Site Close-Out Visit.   
• 
The Site Initiation Visit enables the Sponsor to thoroughly review the study protocol and 
CRFs with the Investigator's staff, in order to assure that the Investigator understands the 
Protocol.  This includes (1) assessing required records and reports; (2) verifying the staff 
has sufficient background, facilities, subject load, time, and willingness to comply with 
the study requirements; is able to submit the Protocol to the IRB/EC for review and 
approval; and can maintain all correspondence, the Protocol, and all required records on 
file; and (3) verifying that the Principal Investigator can submit required reports, 
assumes responsibility for the investigation at his or her institution (which may include 
supervision of some tasks), and has sufficient experience with the study population. 
• 
Site Monitoring Visits will be scheduled depending on the rate of subject enrollment. 
During the Site Monitoring Visit, the monitor will review the CRFs of each subject in 
the study to make certain that the data provided are accurate and obtained in the manner 
specified in the Protocol.  The subjects' clinical records will be reviewed to confirm that 
the case report form data are consistent with the Investigator’s clinical records, the 
background data and concurrent medication are documented in the CRFs, and that there 
is an accurate account of the use of the investigational device in the treatment.   The Site 
Study Binder and other study documents will be reviewed.  The subjects' clinical records 
will be reviewed to determine whether recording of adverse events has been omitted in 
the CRFs.  If this is found to be so, the CRFs will be returned to the Investigator and 
corrected to include this information. During the course of the study, the Sponsor shall 
be available to discuss, in person or by telephone, questions regarding adverse effects, 
removal of subjects from the study, conduct of the study, etc. 
• 
At the completion or termination of this study a Site Close-Out Visit will be conducted. 
17.0 
DATA MANAGEMENT 
17.1 
RECORD RETENTION 
It is required that a copy of all records (e.g., informed consent documents, source 
documents, safety reports, study device dispensing record, etc.) which support CRFs for this 
study, be retained in the files of the responsible Investigator for the latter of the following: 
 At least two (2) years after study completion 
 At least two (2) years after Sponsor receives approval from the local governing 
regulatory authority 
 For the period required by the local governing authority and reviewing IRB/EC. 
Sponsor is to be advised prior to destruction of study records and notified if study records 
are moved to an off-site location for archiving. 

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If the Principal Investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will 
accept the responsibility.  Vascular Dynamics, Inc. must be notified in writing of the name 
and address of the new custodian. 
18.0 
PROTOCOL AMENDMENTS 
An amendment to the Protocol may be proposed by the Sponsor, or by an Investigator with 
prior Sponsor approval.  The amendment must be submitted to the IRB/EC and its 
implementation can take place only after IRB/EC approval. 
19.0 
PROTOCOL DEVIATIONS 
The Investigator will not deviate from the Investigational Plan without the prior written 
approval of Vascular Dynamics, Inc., except in medical emergencies or in unforeseen, 
isolated instances where minor changes are made that will not increase the subject’s risk or 
affect the validity of the investigation.  In medical emergencies, prior approval for 
Investigational Plan deviations will not be required, but Vascular Dynamics, Inc.’s clinical 
research personnel must be notified within five (5) days of the incident. 
All deviations from the Protocol that occur during the study will be captured and the impact 
of the Protocol deviations on the validity of the clinical study reports will be discussed in the 
final clinical study report. 
20.0 
DEVICE ACCOUNTABILITY 
Complete traceability records will be kept of all investigational devices during the study.  
The MobiusHD system and the applicable accessories will be provided by Vascular 
Dynamics, Inc. The device number will be documented in subject medical records, CRFs 
and in the center’s logs. 
Each Investigator will be responsible for the safe storage with restricted access of the 
investigational materials in their possession, to prevent use of investigational materials by 
any persons not participating in the study. 
After completion of the study, all unused investigational devices must be returned in their 
original packaging to Vascular Dynamics, Inc., 2134 Old Middlefield Way, Suite J, 
Mountain View, CA  94043. 
All Investigators will be responsible for using the investigational device according to the 
IFU and Protocol and for maintaining product inventory and records. 
21.0 
INFORMED CONSENT PROCESS 
Informed consent shall be obtained in writing from each study subject or legal guardian and 
the process shall be documented before any procedure specific to the clinical investigation is 
applied to the subject. 

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The subject will be asked to read the Informed Consent Form (ICF) and to sign the form to 
indicate consent to participate in the study.  
The research nature of the study will be explained carefully to the subject.  The scope and 
aims of the research will be described together with known or foreseeable benefits, risks and 
discomforts that subjects may experience.  Appropriate alternative treatments will be 
discussed so that the subject may determine whether or not he or she wishes to participate in 
the study.  The subject must understand that throughout the study his or her participation 
remains voluntary and protected by the Declaration of Helsinki.  The Investigator is 
responsible for obtaining written (or witnessed) informed consent from potential subjects 
prior to study entry.  Subjects will be given time to read the ICF consent and ask any 
questions before being asked to sign the form.  The ICF (approved by the Sponsor and the 
IRB/EC) must be signed and dated by the subject and the Investigator.  The Investigator will 
retain the original signed ICF, give one copy to the subject, and send a second copy to the 
referring Investigator (if applicable).  
Subjects may withdraw their consent to participate in the study at any time without 
prejudice.  The Investigator may withdraw a subject if, in his or her clinical judgment, it is 
in the best interest of the subject, or if the subject cannot comply with the protocol.  
Attempts should be made to complete any examinations and the Sponsor must be notified of 
all withdrawals.  
Should a Protocol amendment be made, the subject's consent form may be revised to reflect 
the changes of the Protocol.  It is the responsibility of the Investigator to ensure that an 
amended ICF is approved or reviewed by the IRB/EC, and that it is signed by all subjects 
subsequently entered in the study, and those currently in the study, if they are affected by the 
amendment.  
If new information becomes available that could significantly affect a subject's future health 
and medical care, the information shall be provided to the subject in written form.  If 
relevant, all affected subjects shall be asked to confirm their continuing informed consent in 
writing. 
22.0 
PREMATURE STUDY TERMINATION 
A subject should be removed from the study whenever considered necessary for his or her 
welfare or when a subject expresses a desire to withdraw from the study.  Non-compliance 
with the Protocol, the occurrence of a SAE or any medical condition that, in the opinion of 
the Investigator, warrants discontinuation from the study for the safety of the subject, may 
necessitate discontinuing a subject.  If a subject is discontinued, the reason must be entered 
on the CRF and signed by the Investigator. In case of any questionable situation, the study 
monitor or Vascular Dynamics, Inc. personnel should be consulted.  When a subject is 
removed from the study as a result of SAE, a final physical examination must be performed.  
Subjects removed from the study because of an AE will be followed-up until the adverse 
event has been resolved. 
In the case that the occurrence of AEs is greater than anticipated, the clinical investigation 
will be suspended; in such a case, a safety committee will be arranged to decide if the study 

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could be continued. The IRB/EC will be notified and the results of the safety committee 
discussions will be brought to the IRB/EC for review and decision. 
Vascular Dynamics, Inc. reserves the right to discontinue any study at any time for 
administrative reasons including, but not limited to, a decision to discontinue further clinical 
investigation of the device, improper conduct of the study by the Investigator, and inability 
to obtain the number of subjects required by the Protocol.  Reimbursements for reasonable 
expenses will be made if such an action is necessary. 
23.0 
REGULATORY AND HEALTH AUTHORITY AUDITS 
The U.S. Food and Drug Administration (FDA), European authorities, and the local state 
health authorities may request access to all study records, including source documents, for 
inspection.  The Investigator and hospital staff are requested to cooperate with these audits.  
The Investigator must notify the Sponsor of any health authority audit as soon as notification 
of such audit is made.  A representative or designee of the Sponsor may also conduct similar 
audits and may be present during health authority audit. 
24.0 
SUBJECT PRIVACY AND CONFIDENTIALITY 
The subject’s name and personal data will remain confidential and will not be published in 
any way.  However, the Sponsor’s monitor or representative and regulatory representatives, 
auditors and inspectors may have access to medical files in order to verify authenticity of 
data collected. 
 
 

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25.0 
BIBLIOGRAPHY 
1.  
Chobanian AV, Bakris GL, Black HR, et al: Joint National Committee on 
Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National 
Heart, Lung, and Blood Institute; National High Blood Pressure Education Program 
Coordinating Committee: Seventh report of the Joint National Committee on 
Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. 
Hypertension. 2003, 42: (6): 1206-1252 
2 . 
Lewington S, Clarke R, Qizilbash N, et al: Prospective Studies Collaboration: Blood 
cholesterol and vascular mortality by age, sex, and blood pressure: A meta-analysis 
of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet. 
2002, 360: (9349): 1903-1913 
3.  
Ong KL, Cheung BM, Man YB, et al: Prevalence, awareness, treatment, and control 
of hypertension among United States adults 1999-2004. Hypertension. 2007, 49: (1): 
69-75. 
4.  
Staessen, J. (2000). Risks of Untreated and Treated Isolated Systolic Hypertension in 
the Elderly: Meta-analysis of Outcome Trials. The Lancet 355 (9207), 865-872. 
5  
Lawes CM, Vander Hoorn S, A Rodgers. International Society of Hypertension: 
Global burden of blood-pressure-related disease, 2001. Lancet. 2008, 371: (9623): 
1513-1518. 
6.  
Vasan RS, Beiser A, Seshadri S, et al: Residual lifetime risk for developing 
hypertension in middle-aged women and men: The Framingham Heart Study. 
JAMA. 2002, 287: (8): 1003-1010. 
7.  
PROGRESS Collaborative Group. Randomised trial of a perindopril-based blood-
pressure-lowering regimen among 6,105 individuals with previous stroke or transient 
ischaemic attack. Lancet. 2001, 358: (9287): 1033-1041. 
8.   
Bagshaw, EA. (1987). Effects of angioplasty upon carotid sinus mechanical 
properties and blood pressure control in the dog. Neurosurgery 21 (3), 324-330. 
9.   
Fadali, EA. (1969). Enlarging the Lumen of the Carotid Sinus. an experimental 
Treatment of Systemic Arterial Hypertension. Archives of Surgery 99 (5), 624-627. 
10. 
McKevitt, EA. (2003). Effect of Treatment of the Carotid Artery Stenosis on Blood 
Pressure: a Comparison of Hemodynamic Disturbances After Carotid 
Endarterectomy and Endovascular Treatment. Stroke 34 (11), 2576-2581. 
11.  
Law, MM. (2009). Use of Blood Pressure Lowering Drugs in the Prevention of 
Cardiovascular Disease: Meta-analysis of 147 Randomized Trials in the Context of 
Expectations from Prospective Epidemiological Studies. BMJ 338, b1665. 
12.  
Fadel, EA. (2003). Recent Insights into Carotid Baroreflex Function in Humans 
Using the Variable Pressure Neck Chamber. Experimental Physiology 88 (6), 671-
680. 

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13.  
Toorop, EA. (2012). Mechanical Stimulation of the Carotid Sinus Baroreflex by an 
Implantable Device: First Experience in Man. Submitted, Available Upon Request. 
14.  
Bates, MM. (2011). Pitfalls of Embolic Protection. Techniques in Vascular and 
Interventional Radiology 14, 101-107. 
 
 

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APPENDIX I: IMAGING GUIDELINES 
 
 

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APPENDIX II: SAMPLE INFORMED CONSENT 
 
 

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APPENDIX III: SAMPLE CASE REPORT FORMS 
 
 
 

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APPENDIX IV: BP MEASUREMENT INSTRUCTIONS 
 
 

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APPENDIX V: CAROTID SINUS MASSAGE INSTRUCTIONS 
 
 
 

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APPENDIX VI: INSTRUCTIONS FOR USE 
 
 

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APPENDIX VII: GUIDELINES FOR THE SIX-MINUTE WALK TEST