VISSIT Intracranial Stent Study for Ischemic Therapy

• Sponsor: Codman & Shurtleff (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00816166
• Collaborator: (none)
• Enrollment: 125
• Arms: 2
• Duration (Months): 68

Study Details

Study Description

Brief Summary

The main objective of this study is to prospectively evaluate the safety, probable benefit, and effectiveness of the PHAROS Vitesse Neurovascular Stent System in a multicenter, randomized clinical trial.

A secondary objective of this study is to evaluate the impact of stenting in the neurovasculature to treat cerebral ischemia on other outcomes such as hospital length of stay, charges, and costs.

Condition or Disease	Intervention/Treatment	Phase
Ischemic Stroke; Transient Ischemic Attack	Device: Pharos Vitesse Neurovascular Stent System (Stent implantation) + Medical therapy (Aspirin and Clopidogrel); Drug: Aspirin and Clopidogrel (Medical therapy)	Phase 2/Phase 3

Detailed Description

1.1 Study Hypothesis Treatment of cerebral or retinal ischemia due to plaque in the neurovasculature using the PHAROS Vitesse Stent System plus medical therapy will provide additional clinical benefit over medical therapy alone.

1.2 Primary Effectiveness Endpoint

The primary effectiveness endpoint consists of a composite of the two following outcomes:

• Stroke in the same territory (distal to the target lesion) as the presenting event within 12 months of randomization

• Hard TIA in the same territory (distal to the target lesion) as the presenting event from day 2 through month 12 post-randomization

1.3 Safety Outcomes

Safety outcomes to be collected and reported as part of the overall risk-to-benefit profile for this device are:

• Stroke in any territory within 30 days of randomization

• Death from any cause within 30 days of randomization

• Hard TIA in any territory occurring after a 24 hour post-procedure stabilization period (days 2-30) since the recovery from anesthesia can mask accurate assessment of possible TIA symptoms.

• Intracranial hemorrhage within 30 days of randomization

1.4 Other Outcomes

• Stent Success - PHAROS Vitesse stent deployed across target lesion with residual stenosis 0-20%

• Percentage of Stent Group Subjects with any (symptomatic or asymptomatic) in-stent restenosis ≥ 70% confirmed by angiogram at 12 months

• Percentage of Stent Group Subjects with symptomatic in-stent restenosis ≥ 70% confirmed by angiogram at 12 months

• Percentage of Medical Therapy Group Subjects with interventional procedure (e.g., angioplasty or stent) at 12 months

• Comparison of NIHSS scores between treatment arms

• Comparison of mRS scores between treatment arms

Study Design

• Study Type: Interventional
• Actual Enrollment: 125 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase III Study of Pharos Vitesse Neurovascular Stent System Compared to Best Medical Therapy for the Treatment of Ischemic Disease
• Study Start Date: Oct 1, 2008
• Actual Primary Completion Date: Apr 1, 2013
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Stent Group Medical therapy + PHAROS Vitesse neurovascular stent ("Stent Group")	Device: Pharos Vitesse Neurovascular Stent System (Stent implantation) + Medical therapy (Aspirin and Clopidogrel); Implantation of one or more balloon-expandable Pharos Vitesse stents to treat neurovascular ischemic lesions + Medical therapy [Treatment with aspirin (81-325 mg daily for the duration of the study) and Clopidogrel (75 mg daily for first 3 months)]; Other Names: Pharos Vitesse Neurovascular Stent System Asprin Clopidogrel Plavix(r)
Active Comparator: Medical Therapy Group Medical therapy alone ("Medical Therapy Group")	Drug: Aspirin and Clopidogrel (Medical therapy); Medical therapy alone [Treatment with aspirin (81-325 mg daily for the duration of the study) and Clopidogrel (75 mg daily for first 3 months)]; Other Names: Aspirin Clopidogrel Plavix(r)

Outcome Measures

Primary Outcome Measures

1. Successful Outcome: No Stroke or Hard TIA in the Same Territory Within 12 Months [One Year]

   The primary effectiveness endpoint was a composite of the two following outcomes: Stroke in the same territory (distal to the target lesion) as the presenting event within 12 months of randomization Hard Transient Ischemic Attack (TIA) in the same territory (distal to the target lesion) as the presenting event from day 2 through month 12 post-randomization A subject was deemed to be a primary endpoint success if neither of these outcomes occurred. The Kaplan-Meier success rate at 12-months post-operatively was calculated with Kaplan-Meier time-to-event methodology, where the time variable for patients who were successful (no stroke within 12 months or hard TIA between 2 days and 12 months) was censored at the time of last follow-up, and the time variable for patients who were not successful (had a stroke within 12 months or hard TIA between 2 days and 12 months) was censored at the time of the first event (stroke with 12 months or hard TIA between 2 days and 12 months).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Subject has at least one neurovascular lesion (70-99%) stenosis [internal carotid, middle cerebral, vertebral artery (C4-BA), and/or basilar artery] symptomatic with a hard TIA or stroke attributable to the territory of the lesion within the past 30 days. An intracranial tandem lesion (50-99%) stenosis may be treated if normal artery segment is sufficient length to avoid overlapping stents.

2. Target vessel diameter / lesion length measurements are within one of the below per angiogram:

• Vessel diameter is ≥ 2.0 mm and < 2.5 mm / lesion length is ≤ 16 mm, or

• Vessel diameter is ≥ 2.5 mm and < 3.0 mm / lesion length is ≤ 18 mm, or

• Vessel diameter is ≥ 3.0 mm and < 4.5 mm / lesion length is ≤ 26 mm, or

• Vessel diameter is ≥ 4.5 mm and ≤ 5.0 mm / lesion length is ≤ 31 mm

1. Subject has normal artery adjacent to each stenosis; diameter 2.0 mm - 5.0 mm

2. Subject age is 18-85 years

3. Life expectancy is at least 2 years

4. Subject 's mRS score is ≤ 3

5. Subject is available for study follow-up visits (e.g., lives within 3 hours of research center)

6. Subject is willing and cognitively able to provide Informed Consent (consent may be indicated verbally and signed by neutral witness if stroke has impaired hand or visual function)

Exclusion Criteria:

1. Subject has contraindications for balloon expandable stent, e.g.

• Extreme tortuosity at, or proximal to, target lesion,

• More than 2 lesions with > 50% stenosis (including vertebral ostia and common carotid disease),

• Carotid or vertebral dissection

1. CT scan or MRI evidence of any of the following:

• Intracranial hemorrhage of type PH1 or PH2

• Subdural or epidural hemorrhage

• Mass effect, or

• Intracranial tumor (except small meningioma)

1. Subject has a previous stent in the territory of the target lesion(s)

2. Subject has a previous coil or clip placed in the territory of the target lesion within 6 months

3. Subject has a potential source of cardiac embolism requiring anticoagulation therapy (e.g., atrial fibrillation, intracardiac thrombus or vegetation, significant mitral stenosis, mechanical heart valve, congestive heart failure with EF <30%, or endocarditis)

4. Subject has concurrent intracranial pathology, e.g.

• Moyamoya

• Vasculitis documented by biopsy results

• Ruptured Aneurysm

• Unruptured aneurysm > 7mm

1. Subject has uncontrolled hypertension (systolic >185 mmHg or diastolic >110 mmHg)

2. Hemoglobin < 10 g/dL; platelet count < 100,000; or INR > 1.5 (e.g., use of warfarin)

3. Subject has an uncorrectable bleeding diathesis

4. Subject's neurological status is unstable and rapidly declining (NIHSS score increased

4 points within 48 hours prior to randomization)

1. Subject has a contraindication for combination antithrombotic treatment (e.g., clopidogrel and aspirin) such as peptic ulcer disease

2. Subject history indicates high risk of non-compliance (e.g., substance abuse, psychosocial issues, etc.)

3. Subject has a known history contraindicating contrast dye or iodine (vs. sensitivity which can be safely controlled by antihistamine, steroid, etc.)

4. Subject is pregnant or plans to become pregnant in the next 12 months

5. Myocardial infarction within past 3 months

6. Treatment with tPA or other thrombolytic agent within 48 hours prior to randomization

7. Major surgery or trauma within 2 weeks prior to randomization

8. Enrollment in another investigational device or drug study that may confound the results

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Codman & Shurtleff

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Berkefeld J, Hamann GF, du Mesnil R, Kurre W, Steinmetz H, Zanella FE, Sitzer M. [Endovascular treatment for intracranial stenoses. A common statement by neurologists and neuroradiologists]. Nervenarzt. 2006 Dec;77(12):1444-55. Review. German.
• Chimowitz MI, Lynn MJ, Howlett-Smith H, Stern BJ, Hertzberg VS, Frankel MR, Levine SR, Chaturvedi S, Kasner SE, Benesch CG, Sila CA, Jovin TG, Romano JG; Warfarin-Aspirin Symptomatic Intracranial Disease Trial Investigators. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med. 2005 Mar 31;352(13):1305-16.
• Cruz-Flores S, Diamond AL. Angioplasty for intracranial artery stenosis. Cochrane Database Syst Rev. 2006 Jul 19;(3):CD004133. Review.
• Derdeyn CP, Chimowitz MI. Angioplasty and stenting for atherosclerotic intracranial stenosis: rationale for a randomized clinical trial. Neuroimaging Clin N Am. 2007 Aug;17(3):355-63, viii-ix. Review.
• Fiorella D, Chow MM, Anderson M, Woo H, Rasmussen PA, Masaryk TJ. A 7-year experience with balloon-mounted coronary stents for the treatment of symptomatic vertebrobasilar intracranial atheromatous disease. Neurosurgery. 2007 Aug;61(2):236-42; discussion 242-3.
• Fiorella D, Woo HH. Emerging endovascular therapies for symptomatic intracranial atherosclerotic disease. Stroke. 2007 Aug;38(8):2391-6. Epub 2007 Jun 21. Review.

• Responsible Party: Codman & Shurtleff
• ClinicalTrials.gov Identifier: NCT00816166
• Other Study ID Numbers: VISSIT CA-2007-01; G080051
• First Posted: Dec 31, 2008
• Last Update Posted: Feb 20, 2015
• Last Verified: Feb 1, 2015

• Keywords provided by Codman & Shurtleff: Ischemic stroke; Transient Ischemic Attack; Intracranial Stenting
• Additional relevant MeSH terms: Ischemic Stroke; Ischemic Attack, Transient; Ischemia; Aspirin; Clopidogrel

Study Results

Participant Flow

Recruitment Details	Subjects were screened and enrolled at 27 sites worldwide (23 sites in the US and 4 sites outside of the US).
Pre-assignment Detail	125 consented,of which 112 were randomized.Of 112,110 were treated (64 Stent Arm & 46 Med Therapy [MT] Arm).Of 112, 111 met criteria & in analysis pop (58 Stent Arm & 53 MT Arm).During course of the study,of 59 randomized to Stent Arm,4 treated w/MT Only & 1 failed to meet eligibility & excluded, & of 53 randomized to MT Arm, 9 treated w/Stent+MT.

Arm/Group Title	Stent Group	Medical Therapy Group
Arm/Group Description	Medical therapy + PHAROS Vitesse neurovascular stent ("Stent Group") Pharos Vitesse Neurovascular Stent System (Stent implantation): Implantation of one or more balloon-expandable Pharos Vitesse stents to treat neurovascular ischemic lesions.	Medical therapy alone ("Medical Therapy Group") Aspirin and Clopidogrel (Medical therapy): Treatment with aspirin (81-325 mg daily for the duration of the study) and Clopidogrel (75 mg daily for first 3 months)
Period Title: Overall Study
STARTED	59	53
ITT Population (Met Eligibility)	58	53
COMPLETED	49	41
NOT COMPLETED	10	12

Baseline Characteristics

Arm/Group Title	Stent Group	Medical Therapy Group	Total
Arm/Group Description	Medical therapy + PHAROS Vitesse neurovascular stent ("Stent Group") Pharos Vitesse Neurovascular Stent System (Stent implantation): Implantation of one or more balloon-expandable Pharos Vitesse stents to treat neurovascular ischemic lesions.	Medical therapy alone ("Medical Therapy Group") Aspirin and Clopidogrel (Medical therapy): Treatment with aspirin (81-325 mg daily for the duration of the study) and Clopidogrel (75 mg daily for first 3 months)	Total of all reporting groups
Overall Participants	58	53	111
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.8 (12.3)	61.8 (12.8)	61.8 (12.5)
Sex: Female, Male (Count of Participants)
Female	17 29.3%	21 39.6%	38 34.2%
Male	41 70.7%	32 60.4%	73 65.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 8.6%	2 3.8%	7 6.3%
Not Hispanic or Latino	53 91.4%	51 96.2%	104 93.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Number) [Number]
Asian	7 12.1%	7 13.2%	14 12.6%
Native Hawaiian or Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 6.9%	5 9.4%	9 8.1%
White	42 72.4%	38 71.7%	80 72.1%
Unknown or Not Reported	5 8.6%	3 5.7%	8 7.2%
Region of Enrollment (participants) [Number]
United States	47 81%	42 79.2%	89 80.2%
China	7 12.1%	7 13.2%	14 12.6%
Austria	4 6.9%	4 7.5%	8 7.2%

Outcome Measures

1. Primary Outcome

Title	Successful Outcome: No Stroke or Hard TIA in the Same Territory Within 12 Months
Description	The primary effectiveness endpoint was a composite of the two following outcomes: Stroke in the same territory (distal to the target lesion) as the presenting event within 12 months of randomization Hard Transient Ischemic Attack (TIA) in the same territory (distal to the target lesion) as the presenting event from day 2 through month 12 post-randomization A subject was deemed to be a primary endpoint success if neither of these outcomes occurred. The Kaplan-Meier success rate at 12-months post-operatively was calculated with Kaplan-Meier time-to-event methodology, where the time variable for patients who were successful (no stroke within 12 months or hard TIA between 2 days and 12 months) was censored at the time of last follow-up, and the time variable for patients who were not successful (had a stroke within 12 months or hard TIA between 2 days and 12 months) was censored at the time of the first event (stroke with 12 months or hard TIA between 2 days and 12 months).
Time Frame	One Year

Outcome Measure Data

Analysis Population Description

Analyses were based on an intent-to-treat (ITT) population, defined as enrolled subjects who met the inclusion/exclusion criteria and who were randomized post angiogram. Stent and Medical Therapy Group subjects were analyzed according to their ITT randomized group regardless of treatment received.

Arm/Group Title	Stent Group	Medical Therapy Group
Arm/Group Description	Medical therapy + PHAROS Vitesse neurovascular stent ("Stent Group") Pharos Vitesse Neurovascular Stent System (Stent implantation): Implantation of one or more balloon-expandable Pharos Vitesse stents to treat neurovascular ischemic lesions.	Medical therapy alone ("Medical Therapy Group") Aspirin and Clopidogrel (Medical therapy): Treatment with aspirin (81-325 mg daily for the duration of the study) and Clopidogrel (75 mg daily for first 3 months)
Measure Participants	58	53
Number (95% Confidence Interval) [percent probability]	62.24	83.68

Adverse Events

Time Frame	Adverse events were collect from time of baseline angiogram/stent procedure through subject end of study (either early termination or 12 month post procedure follow up visit)
Adverse Event Reporting Description	Adverse events collected and were summarized according to how they were reported by investigational sites
Arm/Group Title	Stent Group		Medical Therapy Group
Arm/Group Description	Medical therapy + PHAROS Vitesse neurovascular stent ("Stent Group") Pharos Vitesse Neurovascular Stent System (Stent implantation): Implantation of one or more balloon-expandable Pharos Vitesse stents to treat neurovascular ischemic lesions.		Medical therapy alone ("Medical Therapy Group") Aspirin and Clopidogrel (Medical therapy): Treatment with aspirin (81-325 mg daily for the duration of the study) and Clopidogrel (75 mg daily for first 3 months)
All Cause Mortality
	Stent Group		Medical Therapy Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Stent Group		Medical Therapy Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/58 (51.7%)		20/53 (37.7%)
Blood and lymphatic system disorders
Lymphadenopathy mediastinal	0/58 (0%)	0	1/53 (1.9%)	1
Thrombocytopenia	0/58 (0%)	0	1/53 (1.9%)	1
Cardiac disorders
Angina pectoris	0/58 (0%)	0	1/53 (1.9%)	1
Atrial fibrillation	0/58 (0%)	0	2/53 (3.8%)	2
Bradycardia	0/58 (0%)	0	1/53 (1.9%)	1
Chest pain	0/58 (0%)	0	2/53 (3.8%)	2
Myocardial infarction	1/58 (1.7%)	1	0/53 (0%)	0
Oedema peripheral	0/58 (0%)	0	1/53 (1.9%)	1
Syncope	0/58 (0%)	0	1/53 (1.9%)	1
Ventricular tachycardia	0/58 (0%)	0	1/53 (1.9%)	1
Ear and labyrinth disorders
Vertigo	1/58 (1.7%)	1	0/53 (0%)	0
Endocrine disorders
Hyperglycaemia	1/58 (1.7%)	1	0/53 (0%)	0
Hypoglycaemia	0/58 (0%)	0	1/53 (1.9%)	1
Gastrointestinal disorders
Abdominal discomfort	0/58 (0%)	0	1/53 (1.9%)	1
Abdominal pain	1/58 (1.7%)	1	0/53 (0%)	0
Colitis ischaemic	0/58 (0%)	0	1/53 (1.9%)	1
Gastrointestinal ulcer haemorrhage	0/58 (0%)	0	1/53 (1.9%)	1
Haematochezia	1/58 (1.7%)	1	0/53 (0%)	0
Nausea	1/58 (1.7%)	1	0/53 (0%)	0
Pancreatitis acute	1/58 (1.7%)	1	0/53 (0%)	0
Vomiting	1/58 (1.7%)	1	0/53 (0%)	0
General disorders
Completed suicide	1/58 (1.7%)	1	0/53 (0%)	0
Death	1/58 (1.7%)	1	0/53 (0%)	0
Medical device pain	0/58 (0%)	0	1/53 (1.9%)	1
Neurological symptom	1/58 (1.7%)	1	0/53 (0%)	0
Stent malfunction	1/58 (1.7%)	1	0/53 (0%)	0
Hepatobiliary disorders
Hepatic cirrhosis	1/58 (1.7%)	1	0/53 (0%)	0
Immune system disorders
Drug hypersensitivity	0/58 (0%)	0	1/53 (1.9%)	1
Infections and infestations
Cellulitis	1/58 (1.7%)	1	0/53 (0%)	0
Clostridium difficile colitis	0/58 (0%)	0	2/53 (3.8%)	2
Infection	1/58 (1.7%)	1	0/53 (0%)	0
Oral candidiasis	0/58 (0%)	0	1/53 (1.9%)	1
Osteomyelitis	0/58 (0%)	0	1/53 (1.9%)	1
Injury, poisoning and procedural complications
Arterial restenosis	2/58 (3.4%)	2	1/53 (1.9%)	1
Fall	0/58 (0%)	0	1/53 (1.9%)	1
Overdose	0/58 (0%)	0	1/53 (1.9%)	1
Vascular pseudoaneurysm	1/58 (1.7%)	1	0/53 (0%)	0
Vascular rupture	1/58 (1.7%)	1	0/53 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/58 (1.7%)	1	0/53 (0%)	0
Hyperkalaemia	1/58 (1.7%)	1	0/53 (0%)	0
Hypokalaemia	1/58 (1.7%)	1	1/53 (1.9%)	1
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	0/58 (0%)	0	1/53 (1.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm malignant	0/58 (0%)	0	1/53 (1.9%)	1
Prostate cancer	0/58 (0%)	0	1/53 (1.9%)	1
Nervous system disorders
Ataxia	1/58 (1.7%)	1	0/53 (0%)	0
Cerebral infarction	2/58 (3.4%)	2	0/53 (0%)	0
Cerebral ischaemia	1/58 (1.7%)	1	0/53 (0%)	0
Cerebrovascular accident	2/58 (3.4%)	2	1/53 (1.9%)	1
Convulsion	1/58 (1.7%)	1	0/53 (0%)	0
Haemorrhage intracranial	1/58 (1.7%)	1	0/53 (0%)	0
Haemorrhagic stroke	2/58 (3.4%)	2	0/53 (0%)	0
Ischaemic stroke	7/58 (12.1%)	7	4/53 (7.5%)	4
Muscular weakness	1/58 (1.7%)	1	0/53 (0%)	0
Neurological symptom	2/58 (3.4%)	2	0/53 (0%)	0
Post procedural stroke	1/58 (1.7%)	1	0/53 (0%)	0
Transient ischaemic attack	0/58 (0%)	0	2/53 (3.8%)	2
Vertebrobasilar insufficiency	1/58 (1.7%)	1	0/53 (0%)	0
Vision blurred	1/58 (1.7%)	1	0/53 (0%)	0
Visual field defect	1/58 (1.7%)	1	0/53 (0%)	0
Psychiatric disorders
Panic attack	1/58 (1.7%)	1	0/53 (0%)	0
Suicide attempt	1/58 (1.7%)	1	0/53 (0%)	0
Renal and urinary disorders
Urinary retention	1/58 (1.7%)	1	0/53 (0%)	0
Urinary tract infection	3/58 (5.2%)	3	1/53 (1.9%)	1
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease	1/58 (1.7%)	1	0/53 (0%)	0
Pneumonia	1/58 (1.7%)	1	1/53 (1.9%)	1
Pneumonia aspiration	2/58 (3.4%)	2	1/53 (1.9%)	1
Surgical and medical procedures
Amputation	1/58 (1.7%)	1	0/53 (0%)	0
Carotid endarterectomy	1/58 (1.7%)	1	0/53 (0%)	0
Hip arthroplasty	0/58 (0%)	0	1/53 (1.9%)	1
Vascular disorders
Aortic aneurysm	0/58 (0%)	0	1/53 (1.9%)	1
Artery dissection	2/58 (3.4%)	2	0/53 (0%)	0
Hypertension	0/58 (0%)	0	1/53 (1.9%)	1
Hypotension	1/58 (1.7%)	1	0/53 (0%)	0
Intermittent claudication	1/58 (1.7%)	1	0/53 (0%)	0
Migraine	0/58 (0%)	0	1/53 (1.9%)	1
Peripheral vascular disorder	1/58 (1.7%)	1	0/53 (0%)	0
Transient ischaemic attack	2/58 (3.4%)	2	4/53 (7.5%)	5
Other (Not Including Serious) Adverse Events
	Stent Group		Medical Therapy Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/58 (63.8%)		34/53 (64.2%)
Blood and lymphatic system disorders
Anaemia	3/58 (5.2%)	3	2/53 (3.8%)	2
Coagulopathy	0/58 (0%)	0	1/53 (1.9%)	1
Haemoglobin decreased	1/58 (1.7%)	1	0/53 (0%)	0
Increased tendency to bruise	0/58 (0%)	0	1/53 (1.9%)	1
Cardiac disorders
Bradycardia	1/58 (1.7%)	1	0/53 (0%)	0
Chest discomfort	0/58 (0%)	0	1/53 (1.9%)	1
Chest pain	0/58 (0%)	0	2/53 (3.8%)	2
Coronary Artery Disease	1/58 (1.7%)	1	1/53 (1.9%)	1
Dizziness	0/58 (0%)	0	1/53 (1.9%)	1
Dizziness postural	0/58 (0%)	0	1/53 (1.9%)	1
Myocardial ischaemia	1/58 (1.7%)	1	0/53 (0%)	0
Oedema peripheral	0/58 (0%)	0	1/53 (1.9%)	1
Presyncope	1/58 (1.7%)	1	0/53 (0%)	0
Syncope	0/58 (0%)	0	1/53 (1.9%)	1
Ventricular tachycardia	0/58 (0%)	0	1/53 (1.9%)	1
Ear and labyrinth disorders
Vertigo	2/58 (3.4%)	2	2/53 (3.8%)	2
Endocrine disorders
Diabetic neuropathy	1/58 (1.7%)	1	0/53 (0%)	0
Diabetic retinopathy	1/58 (1.7%)	1	0/53 (0%)	0
Hyperglycaemia	3/58 (5.2%)	3	0/53 (0%)	0
Hypoglycaemia	1/58 (1.7%)	1	0/53 (0%)	0
Eye disorders
Eye pain	0/58 (0%)	0	1/53 (1.9%)	1
Retinal haemorrhage	0/58 (0%)	0	1/53 (1.9%)	1
Visual field defect	1/58 (1.7%)	1	0/53 (0%)	0
Dysphagia	0/58 (0%)	0	1/53 (1.9%)	1
Gastrointestinal disorders
Abdominal distension	1/58 (1.7%)	1	0/53 (0%)	0
Barrett s oesophagus	0/58 (0%)	0	1/53 (1.9%)	1
Constipation	5/58 (8.6%)	5	1/53 (1.9%)	1
Dyspepsia	2/58 (3.4%)	2	1/53 (1.9%)	1
Gastrointestinal disorder	1/58 (1.7%)	1	0/53 (0%)	0
Haematochezia	0/58 (0%)	0	1/53 (1.9%)	1
Hiatus hernia	0/58 (0%)	0	1/53 (1.9%)	1
Inguinal hernia	1/58 (1.7%)	1	0/53 (0%)	0
Mouth haemorrhage	1/58 (1.7%)	1	0/53 (0%)	0
Nausea	0/58 (0%)	0	2/53 (3.8%)	2
Oropharyngeal pain	0/58 (0%)	0	1/53 (1.9%)	1
Post procedural diarrhoea	1/58 (1.7%)	1	0/53 (0%)	0
General disorders
Fatigue	2/58 (3.4%)	2	0/53 (0%)	0
Influenza like illness	0/58 (0%)	0	1/53 (1.9%)	1
Lethargy	0/58 (0%)	0	1/53 (1.9%)	1
Localised oedema	0/58 (0%)	0	1/53 (1.9%)	1
Malaise	0/58 (0%)	0	1/53 (1.9%)	1
Neurological complication associated with device	1/58 (1.7%)	1	0/53 (0%)	0
Pain	0/58 (0%)	0	1/53 (1.9%)	1
Pyrexia	1/58 (1.7%)	1	0/53 (0%)	0
Infections and infestations
Escherichia urinary tract infection	1/58 (1.7%)	1	0/53 (0%)	0
Helicobacter infection	0/58 (0%)	0	1/53 (1.9%)	1
Herpes zoster	1/58 (1.7%)	1	1/53 (1.9%)	1
Infection	0/58 (0%)	0	1/53 (1.9%)	1
Oral candidiasis	1/58 (1.7%)	1	0/53 (0%)	0
Injury, poisoning and procedural complications
Arterial restenosis	1/58 (1.7%)	1	0/53 (0%)	0
Fall	6/58 (10.3%)	6	4/53 (7.5%)	4
Phlebitis	1/58 (1.7%)	1	0/53 (0%)	0
Post procedural haematuria	1/58 (1.7%)	1	1/53 (1.9%)	1
Procedural hypotension	1/58 (1.7%)	1	0/53 (0%)	0
Procedural nausea	2/58 (3.4%)	2	1/53 (1.9%)	1
Procedural pain	1/58 (1.7%)	1	1/53 (1.9%)	1
Procedural vomiting	1/58 (1.7%)	1	0/53 (0%)	0
Investigations
Blood creatine increased	1/58 (1.7%)	1	0/53 (0%)	0
Blood glucose fluctuation	0/58 (0%)	0	1/53 (1.9%)	1
Blood glucose increased	1/58 (1.7%)	1	0/53 (0%)	0
Blood potassium abnormal	1/58 (1.7%)	1	0/53 (0%)	0
Blood potassium decreased	1/58 (1.7%)	1	0/53 (0%)	0
Blood testosterone decreased	1/58 (1.7%)	1	0/53 (0%)	0
Hepatic enzyme increased	1/58 (1.7%)	1	0/53 (0%)	0
Neurological examination abnormal	0/58 (0%)	0	1/53 (1.9%)	1
Radial pulse decreased	0/58 (0%)	0	1/53 (1.9%)	1
Red blood cell sedimentation rate increased	0/58 (0%)	0	1/53 (1.9%)	1
Transaminases increased	1/58 (1.7%)	1	0/53 (0%)	0
Metabolism and nutrition disorders
Decreased appetite	1/58 (1.7%)	1	0/53 (0%)	0
Dehydration	1/58 (1.7%)	1	1/53 (1.9%)	1
Hyperlipidaemia	0/58 (0%)	0	1/53 (1.9%)	1
Hypokalaemia	3/58 (5.2%)	3	1/53 (1.9%)	1
Vitamin B12 deficiency	1/58 (1.7%)	1	0/53 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	1/58 (1.7%)	1	0/53 (0%)	0
Back Pain	3/58 (5.2%)	3	0/53 (0%)	0
Intervertebral disc degeneration	1/58 (1.7%)	1	0/53 (0%)	0
Joint dislocation	1/58 (1.7%)	1	0/53 (0%)	0
Joint swelling	2/58 (3.4%)	2	1/53 (1.9%)	1
Neck pain	0/58 (0%)	0	1/53 (1.9%)	1
Pain in extremity	1/58 (1.7%)	1	1/53 (1.9%)	1
Wrist fracture	0/58 (0%)	0	1/53 (1.9%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Skin cancer	1/58 (1.7%)	1	0/53 (0%)	0
Nervous system disorders
Aphasia	0/58 (0%)	0	1/53 (1.9%)	1
Carpal tunnel syndrome	1/58 (1.7%)	1	1/53 (1.9%)	1
Cerebral artery stenosis	0/58 (0%)	0	1/53 (1.9%)	1
Cerebral haemorrhage	1/58 (1.7%)	1	0/53 (0%)	0
Cerebral infarction	0/58 (0%)	0	1/53 (1.9%)	1
Diabetic gastroparesis	1/58 (1.7%)	1	0/53 (0%)	0
Diplopia	0/58 (0%)	0	1/53 (1.9%)	1
Dysarthria	1/58 (1.7%)	1	1/53 (1.9%)	1
Headache	4/58 (6.9%)	5	3/53 (5.7%)	4
Hemiparesis	2/58 (3.4%)	2	0/53 (0%)	0
Ischaemic stroke	2/58 (3.4%)	2	0/53 (0%)	0
Neuralgia	2/58 (3.4%)	3	0/53 (0%)	0
Neurological symptom	0/58 (0%)	0	1/53 (1.9%)	1
Paraesthesia	3/58 (5.2%)	4	2/53 (3.8%)	2
Post stroke depression	2/58 (3.4%)	2	1/53 (1.9%)	1
Procedural headache	1/58 (1.7%)	1	1/53 (1.9%)	1
Somnolence	1/58 (1.7%)	1	1/53 (1.9%)	1
VIIth nerve paralysis	0/58 (0%)	0	1/53 (1.9%)	1
Vision blurred	0/58 (0%)	0	1/53 (1.9%)	1
Psychiatric disorders
Anxiety	0/58 (0%)	0	1/53 (1.9%)	1
Confusional state	2/58 (3.4%)	2	0/53 (0%)	0
Depression	2/58 (3.4%)	2	1/53 (1.9%)	1
Insomnia	0/58 (0%)	0	1/53 (1.9%)	1
Memory impairment	1/58 (1.7%)	1	1/53 (1.9%)	1
Withdrawal syndrome	0/58 (0%)	0	1/53 (1.9%)	1
Renal and urinary disorders
Dysuria	1/58 (1.7%)	1	0/53 (0%)	0
Haematuria	0/58 (0%)	0	1/53 (1.9%)	1
Micturition urgency	1/58 (1.7%)	1	0/53 (0%)	0
Post procedural haematuria	1/58 (1.7%)	1	0/53 (0%)	0
Renal cyst	1/58 (1.7%)	1	0/53 (0%)	0
Renal failure	0/58 (0%)	0	1/53 (1.9%)	1
Renal failure acute	1/58 (1.7%)	1	0/53 (0%)	0
Urinary Retention	2/58 (3.4%)	2	0/53 (0%)	0
Urinary tract infection	5/58 (8.6%)	5	1/53 (1.9%)	2
Reproductive system and breast disorders
Benign prostatic hyperplasia	2/58 (3.4%)	2	0/53 (0%)	0
Breast Mass	1/58 (1.7%)	1	0/53 (0%)	0
Respiratory, thoracic and mediastinal disorders
Atelectasis	1/58 (1.7%)	1	1/53 (1.9%)	1
Bronchitis	1/58 (1.7%)	1	0/53 (0%)	0
Dyspnoea	0/58 (0%)	0	1/53 (1.9%)	2
Pneumonia	0/58 (0%)	0	1/53 (1.9%)	1
Pulmonary mass	0/58 (0%)	0	1/53 (1.9%)	1
Radiation pneumonitis	0/58 (0%)	0	1/53 (1.9%)	1
Sinus congestion	0/58 (0%)	0	1/53 (1.9%)	1
Sinusitis	2/58 (3.4%)	2	2/53 (3.8%)	2
Upper Respiratory Tract Infection	2/58 (3.4%)	2	1/53 (1.9%)	1
Upper respiratory tract congestion	1/58 (1.7%)	1	0/53 (0%)	0
Skin and subcutaneous tissue disorders
Dry gangrene	1/58 (1.7%)	1	0/53 (0%)	0
Pruritus	0/58 (0%)	0	1/53 (1.9%)	1
Rash	3/58 (5.2%)	3	2/53 (3.8%)	2
Rash macular	0/58 (0%)	0	1/53 (1.9%)	1
Surgical and medical procedures
Cataract operation	1/58 (1.7%)	1	0/53 (0%)	0
Tooth extraction	1/58 (1.7%)	1	0/53 (0%)	0
Vascular disorders
Artery dissection	2/58 (3.4%)	2	0/53 (0%)	0
Contusion	1/58 (1.7%)	1	0/53 (0%)	0
Epistaxis	1/58 (1.7%)	1	1/53 (1.9%)	1
Haematoma	0/58 (0%)	0	2/53 (3.8%)	2
Hypertension	7/58 (12.1%)	9	7/53 (13.2%)	10
Hypotension	1/58 (1.7%)	1	0/53 (0%)	0
Orthostatic hypotension	1/58 (1.7%)	1	0/53 (0%)	0
Post procedural haematoma	3/58 (5.2%)	4	0/53 (0%)	0
Post procedural haemorrhage	1/58 (1.7%)	1	1/53 (1.9%)	1
Subclavian artery stenosis	1/58 (1.7%)	1	0/53 (0%)	0
Transient ischaemic attack	2/58 (3.4%)	2	8/53 (15.1%)	12
Vasospasm	4/58 (6.9%)	4	0/53 (0%)	0
Venous thrombosis	1/58 (1.7%)	1	0/53 (0%)	0

Limitations/Caveats

Early termination of enrollment led to small numbers of subjects analyzed (less than 50% of the prospectively planned sample size). Various endpoints, subgroup and sensitivity analyses were not conducted because the study was not fully enrolled.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.