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REDUCE: GORE® Septal Occluder Device for Patent Foramen Ovale (PFO) Closure in Stroke Patients

Sponsor
W.L.Gore & Associates (Industry)
Overall Status
Completed
CT.gov ID
NCT00738894
Collaborator
(none)
664
Enrollment
2
Locations
2
Arms
137
Actual Duration (Months)
332
Patients Per Site
2.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective is to determine if patent foramen ovale (PFO) closure with the GORE® HELEX® Septal Occluder or GORE® CARDIOFORM Septal Occluder plus antiplatelet medical management is safe and effective and reduces the risk of recurrent stroke or imaging-confirmed transient ischemic attack (TIA) when compared to antiplatelet medical management alone in patients with a PFO and history of cryptogenic stroke or imaging-confirmed TIA.

A co-primary objective is to demonstrate that medical management plus closure with the study device reduces the risk of new brain infarct compared to medical management alone.

Condition or Disease Intervention/Treatment Phase
  • Device: Septal Occluder Device
  • Drug: Antiplatelet Medical Therapy
 N/A

Study Design

Study Type:
Interventional
Actual Enrollment :
664 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
GORE® HELEX® Septal Occluder / GORE® CARDIOFORM Septal Occluder and Antiplatelet Medical Management for Reduction of Recurrent Stroke or Imaging-Confirmed TIA in Patients With Patent Foramen Ovale (PFO) - The Gore REDUCE Clinical Study
Actual Study Start Date :
Dec 10, 2008
Actual Primary Completion Date :
Apr 24, 2017
Actual Study Completion Date :
May 11, 2020

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Medical Management

Antiplatelet medical therapy alone

Drug: Antiplatelet Medical Therapy
Investigator's choice of one of three regimen options specified in protocol
Other Names:
  • Aspirin
  • Dipyridamole
  • Aggrenox
  • Clopidogrel
  • Plavix

    		•
    Experimental: Device Closure

    PFO closure with study septal occluder device plus antiplatelet medical therapy

    Device: Septal Occluder Device
    PFO closure with study septal occluder device
    Other Names:
  • GORE® HELEX® Septal Occluder
  • GORE® CARDIOFORM Septal Occluder

    • Drug: Antiplatelet Medical Therapy
    Investigator's choice of one of three regimen options specified in protocol
    Other Names:
  • Aspirin
  • Dipyridamole
  • Aggrenox
  • Clopidogrel
  • Plavix

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Subjects With Freedom From Recurrent Ischemic Stroke (Primary Outcome #1) [24 months]

      A recurrent stroke event was defined as the first occurrence post-randomization of either a) neurological deficit presumed due to ischemia and persisting longer than 24 hours or until death, or b) transient neurological deficit presumed due to ischemia, persisting less than 24 hours with MRI evidence of a new relevant brain infarction.

    2. Number of Subjects With New Brain Infarct or Recurrent Stroke (Primary Outcome #2) [24 months]

      Responders were subjects who showed one or more new infarctions on MRI since screening, or experienced a confirmed recurrent stroke, through 24 months (913 days). Nonresponders were subjects who did not show new infarction on MRI since screening and were confirmed free of recurrent stroke through at least 549 days. An infarction was defined as a new (since screening) T2 hyperintense MRI lesion with diameter ≥ 3 mm.

    Secondary Outcome Measures

    1. Number of Subjects With Study-related Serious Adverse Events [24 months]

      Adverse event seriousness and relationship to study treatments (device, procedure, or antiplatelet medical therapy) as reported by each investigative site

    2. Number of Subjects With Effective Closure in Test (Device) Arm [24 months]

      Assessment of PFO closure in test (device) arm subjects by transesophageal echocardiography (TEE) at 24-month follow-up. Effective closure defined as occluded, small, or moderate shunt (0-25 bubbles).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Presence of cryptogenic ischemic stroke or TIA of presumed embolic infarction verified by a neurologist within 180 days prior to randomization

    • Presence of Patent Foramen Ovale (PFO), as determined initially by positive bubble study utilizing transesophageal echocardiography (TEE), demonstrating spontaneous right-to-left shunting or right-to-left shunting during Valsalva maneuver.

    • Absence of an identifiable source of thromboembolism in the systemic circulation

    • No evidence of a hypercoagulable state

    • Note: Additional Inclusion Criteria may apply

    Exclusion Criteria:

    • Other co-morbidities including, but not limited to, mural thrombus, dilated cardiomyopathy, atrial fibrillation/flutter, cardiac prosthetics (valves), mitral valve stenosis, aortic dissection, significant atherosclerosis, vasculitis, pre-existing neurologic disorders, multiple sclerosis, arteriovenous malformations, prior intracranial hemorrhage, severe central nervous system (CNS) disease, severe disability related to prior stroke, and autoimmune disorders that would increase the risk of mortality or morbidity above what is typical for the treatment

    • Previous Myocardial Infarction

    • Active infection that cannot be treated successfully prior to randomization

    • Sensitivity or contraindication to all proposed medical treatments

    • Pregnancy or intent on becoming pregnant through 24-months after randomization

    • Indications outside the parameters accepted for placement of the GORE® HELEX® Septal Occluder / GORE® Septal Occluder, including extensive congenital cardiac anomalies and defect diameter estimated to be > 18mm

    • Atrial septal anatomy that is expected to necessitate placement of more than one GORE® HELEX® Septal Occluder / GORE® CARDIOFORM Septal Occluder

    • Need for concomitant procedure(s) that may confound detection of adverse events related to device placement

    • Note: Additional Exclusion Criteria may apply

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Pennsylvania Medical Center Philadelphia Pennsylvania United States 19104
    2 Rigshospitalet Copenhagen Denmark

    Sponsors and Collaborators

    • W.L.Gore & Associates

    Investigators

    • Principal Investigator: Scott E. Kasner, MD, FAHA, University of Pennsylvania Medical Center
    • Principal Investigator: John F. Rhodes, MD, Medical University of South Carolina
    • Principal Investigator: Lars Søndergaard, MD, Rigshospitalet, Denmark

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    W.L.Gore & Associates
    ClinicalTrials.gov Identifier:
    NCT00738894
    Other Study ID Numbers:
    • HLX 06-03
    First Posted:
    Aug 21, 2008
    Last Update Posted:
    Nov 20, 2020
    Last Verified:
    Oct 1, 2020
    Keywords provided by W.L.Gore & Associates
    cryptogenic
    stroke
    transient ischemic attack
    TIA
    PFO
    Patent foramen ovale
    HELEX
    Septal Occluder
    PFO Occluder
    Additional relevant MeSH terms:
    Stroke
    Ischemic Attack, Transient
    Foramen Ovale, Patent
    Aspirin
    Dipyridamole
    Clopidogrel

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Device Closure Medical Management
    Arm/Group Description PFO closure with study septal occluder device plus antiplatelet medical therapy Septal Occluder Device: GORE® HELEX® Septal Occluder or GORE® CARDIOFORM Septal Occluder Antiplatelet Medical Therapy: Investigator's choice of one of three regimen options specified in protocol Antiplatelet medical therapy alone Antiplatelet Medical Therapy: Investigator's choice of one of three regimen options specified in protocol
    Period Title: Overall Study
    STARTED 441 223
    COMPLETED 402 190
    NOT COMPLETED 39 33

    Baseline Characteristics

    Arm/Group Title Device Closure Medical Management Total
    Arm/Group Description PFO closure with study septal occluder device plus antiplatelet medical therapy Septal Occluder Device: GORE® HELEX® Septal Occluder or GORE® CARDIOFORM Septal Occluder Antiplatelet Medical Therapy: Investigator's choice of one of three regimen options specified in protocol Antiplatelet medical therapy alone Antiplatelet Medical Therapy: Investigator's choice of one of three regimen options specified in protocol Total of all reporting groups
    Overall Participants 441 223 664
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    45.4
    (9.3)
    44.8
    (9.6)
    45.2
    (9.4)
    Sex: Female, Male (Count of Participants)
    Female
    180
    40.8%
    85
    38.1%
    265
    39.9%
    Male
    261
    59.2%
    138
    61.9%
    399
    60.1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    22
    5%
    9
    4%
    31
    4.7%
    Not Hispanic or Latino
    413
    93.7%
    213
    95.5%
    626
    94.3%
    Unknown or Not Reported
    6
    1.4%
    1
    0.4%
    7
    1.1%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    2
    0.5%
    0
    0%
    2
    0.3%
    Asian
    0
    0%
    2
    0.9%
    2
    0.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    14
    3.2%
    12
    5.4%
    26
    3.9%
    White
    412
    93.4%
    203
    91%
    615
    92.6%
    More than one race
    3
    0.7%
    1
    0.4%
    4
    0.6%
    Unknown or Not Reported
    10
    2.3%
    5
    2.2%
    15
    2.3%
    Region of Enrollment (Count of Participants)
    United States
    216
    49%
    115
    51.6%
    331
    49.8%
    Canada
    17
    3.9%
    8
    3.6%
    25
    3.8%
    Denmark
    79
    17.9%
    38
    17%
    117
    17.6%
    Finland
    18
    4.1%
    8
    3.6%
    26
    3.9%
    Norway
    25
    5.7%
    14
    6.3%
    39
    5.9%
    Sweden
    64
    14.5%
    31
    13.9%
    95
    14.3%
    United Kingdom
    22
    5%
    9
    4%
    31
    4.7%
    Time from qualifying event to randomization (days) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [days]
    100
    (52)
    101
    (53)
    101
    (53)
    Current smoking (Count of Participants)
    Count of Participants [Participants]
    63
    14.3%
    25
    11.2%
    88
    13.3%
    Hypertension (Count of Participants)
    Count of Participants [Participants]
    112
    25.4%
    58
    26%
    170
    25.6%
    Diabetes mellitus (Count of Participants)
    Count of Participants [Participants]
    18
    4.1%
    10
    4.5%
    28
    4.2%
    Stroke or TIA before index event (Count of Participants)
    Previous either
    62
    14.1%
    23
    10.3%
    85
    12.8%
    Previous stroke
    42
    9.5%
    13
    5.8%
    55
    8.3%
    Previous TIA
    26
    5.9%
    11
    4.9%
    37
    5.6%
    Index event (Count of Participants)
    Stroke w/ symptoms >=24 hr
    402
    91.2%
    199
    89.2%
    601
    90.5%
    Stroke symptoms <24 hr, w/ imaging confirmation
    39
    8.8%
    24
    10.8%
    63
    9.5%
    Patent foramen ovale shunt size (Count of Participants)
    Small (1-5 bubbles)
    77
    17.5%
    43
    19.3%
    120
    18.1%
    Moderate (6-25 bubbles)
    166
    37.6%
    94
    42.2%
    260
    39.2%
    Large (>25 bubbles)
    182
    41.3%
    79
    35.4%
    261
    39.3%
    Atrial septal aneurysm (Count of Participants)
    Count of Participants [Participants]
    86
    19.5%
    86
    38.6%

    Outcome Measures

    1. Primary Outcome
    Title Number of Subjects With Freedom From Recurrent Ischemic Stroke (Primary Outcome #1)
    Description A recurrent stroke event was defined as the first occurrence post-randomization of either a) neurological deficit presumed due to ischemia and persisting longer than 24 hours or until death, or b) transient neurological deficit presumed due to ischemia, persisting less than 24 hours with MRI evidence of a new relevant brain infarction.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    Intention to Treat: includes all subjects randomized
    Arm/Group Title Device Closure Medical Management
    Arm/Group Description PFO closure with study septal occluder device plus antiplatelet medical therapy Septal Occluder Device: GORE® HELEX® Septal Occluder or GORE® CARDIOFORM Septal Occluder Antiplatelet Medical Therapy: Investigator's choice of one of three regimen options specified in protocol Antiplatelet medical therapy alone Antiplatelet Medical Therapy: Investigator's choice of one of three regimen options specified in protocol
    Measure Participants 441 223
    Count of Participants [Participants]
    6
    1.4%
    12
    5.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Device Closure, Medical Management
    Comments Test null hypothesis of equal or lower recurrent stroke-free survivorship for device closure compared to medical management. H0: Sd(t) ≤ Sm(t) for all t, versus H1: Sd(t) > Sm(t) for all t, where Sd(t) and Sm(t) are true Kaplan-Meier product-limit survivor functions for the device closure and medical management arms and t is time from randomization to event or censoring. Event-free subjects were censored at time of last follow-up. Significance threshold (1-sided alpha) = 0.025.
    Type of Statistical Test Superiority
    Comments This is the first of two primary outcomes for this study. Assumptions for power calculations: expected event free for medical management 92% at 24 months; expected event free for device closure 96.4% at 24 months (55% risk reduction); 664 subjects randomly assigned 2:1 to device closure or medical management provides 80% power with 15% attrition (over 5 years) and 1-sided alpha = 0.024 to allow for interim analysis (interim analysis later rescinded from plan).
    Statistical Test of Hypothesis p-Value 0.001
    Comments 1-sided p-value was adjusted for multiplicity with 2nd primary outcome using Dubey and Armitage-Parmer (D/AP) procedure.
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.23
    Confidence Interval (2-Sided) 95%
    0.09 to 0.62
    Parameter Dispersion Type:
    Value:
    Estimation Comments Hazard ratio (test/control) obtained from Cox proportional hazards model with treatment arm as sole explanatory variable, the exponentiated coefficient of which provided the hazard ratio. Unadjusted for multiplicity.
    2. Primary Outcome
    Title Number of Subjects With New Brain Infarct or Recurrent Stroke (Primary Outcome #2)
    Description Responders were subjects who showed one or more new infarctions on MRI since screening, or experienced a confirmed recurrent stroke, through 24 months (913 days). Nonresponders were subjects who did not show new infarction on MRI since screening and were confirmed free of recurrent stroke through at least 549 days. An infarction was defined as a new (since screening) T2 hyperintense MRI lesion with diameter ≥ 3 mm.
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    Intention to Treat: includes all subjects randomized and evaluated for brain infarct
    Arm/Group Title Device Closure Medical Management
    Arm/Group Description PFO closure with study septal occluder device plus antiplatelet medical therapy Septal Occluder Device: GORE® HELEX® Septal Occluder or GORE® CARDIOFORM Septal Occluder Antiplatelet Medical Therapy: Investigator's choice of one of three regimen options specified in protocol Antiplatelet medical therapy alone Antiplatelet Medical Therapy: Investigator's choice of one of three regimen options specified in protocol
    Measure Participants 383 177
    Count of Participants [Participants]
    22
    5%
    20
    9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Device Closure, Medical Management
    Comments Test null hypothesis of equal or higher proportion with brain infarct for device closure compared to medical management. H0: Pm - Pd ≤ 0, versus H1: Pm - Pd > 0, where Pd and Pm are true proportions of subjects with brain infarct for the device closure and medical management arms. Significance threshold (1-sided alpha) = 0.025.
    Type of Statistical Test Superiority
    Comments This is the second of two primary outcomes for this study. Assumptions for power calculations: expected proportion of brain infarct is 3-7 times the clinical stroke rate; expected brain infarct proportion for medical management 14.5% (2.9% clinical stroke x 5); expected brain infarct for device closure 6.5% (55% risk reduction); 597 subjects (10% attrition from 664) provides 73% power with 1-sided alpha = 0.0125 (based conservatively on a Bonferroni adjustment of alpha/2).
    Statistical Test of Hypothesis p-Value 0.024
    Comments 1-sided p-value was adjusted for multiplicity with 1st primary outcome using Dubey and Armitage-Parmer (D/AP) procedure.
    Method z-test, 1-sided
    Comments
    Method of Estimation Estimation Parameter Risk Difference (RD)
    Estimated Value 0.056
    Confidence Interval (2-Sided) 95%
    0.003 to 0.108
    Parameter Dispersion Type:
    Value:
    Estimation Comments Unadjusted for multiplicity.
    3. Secondary Outcome
    Title Number of Subjects With Study-related Serious Adverse Events
    Description Adverse event seriousness and relationship to study treatments (device, procedure, or antiplatelet medical therapy) as reported by each investigative site
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    Intention to Treat: all subjects randomized
    Arm/Group Title Device Closure Medical Management
    Arm/Group Description PFO closure with study septal occluder device plus antiplatelet medical therapy Septal Occluder Device: GORE® HELEX® Septal Occluder or GORE® CARDIOFORM Septal Occluder Antiplatelet Medical Therapy: Investigator's choice of one of three regimen options specified in protocol Antiplatelet medical therapy alone Antiplatelet Medical Therapy: Investigator's choice of one of three regimen options specified in protocol
    Measure Participants 441 223
    Count of Participants [Participants]
    102
    23.1%
    62
    27.8%
    4. Secondary Outcome
    Title Number of Subjects With Effective Closure in Test (Device) Arm
    Description Assessment of PFO closure in test (device) arm subjects by transesophageal echocardiography (TEE) at 24-month follow-up. Effective closure defined as occluded, small, or moderate shunt (0-25 bubbles).
    Time Frame 24 months

    Outcome Measure Data

    Analysis Population Description
    All subjects randomized to test (device) arm with 24-month PFO closure assessment
    Arm/Group Title Device Closure
    Arm/Group Description PFO closure with study septal occluder device plus antiplatelet medical therapy Septal Occluder Device: GORE® HELEX® Septal Occluder or GORE® CARDIOFORM Septal Occluder Antiplatelet Medical Therapy: Investigator's choice of one of three regimen options specified in protocol
    Measure Participants 318
    Count of Participants [Participants]
    312
    70.7%

    Adverse Events

    Time Frame 24 months
    Adverse Event Reporting Description
    Arm/Group Title Device Closure Medical Management
    Arm/Group Description PFO closure with study septal occluder device plus antiplatelet medical therapy Septal Occluder Device: GORE® HELEX® Septal Occluder or GORE® CARDIOFORM Septal Occluder Antiplatelet Medical Therapy: Investigator's choice of one of three regimen options specified in protocol Antiplatelet medical therapy alone Antiplatelet Medical Therapy: Investigator's choice of one of three regimen options specified in protocol
    All Cause Mortality
    Device Closure Medical Management
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 2/441 (0.5%) 0/223 (0%)
    Serious Adverse Events
    Device Closure Medical Management
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 102/441 (23.1%) 62/223 (27.8%)
    Cardiac disorders
    Atrial fibrillation 10/441 (2.3%) 1/223 (0.4%)
    Palpitations 2/441 (0.5%) 0/223 (0%)
    Acute myocardial infarction 0/441 (0%) 1/223 (0.4%)
    Angina pectoris 0/441 (0%) 1/223 (0.4%)
    Atrial flutter 1/441 (0.2%) 0/223 (0%)
    Bradycardia 1/441 (0.2%) 0/223 (0%)
    Cardiac arrest 1/441 (0.2%) 0/223 (0%)
    Cardiac tamponade 1/441 (0.2%) 0/223 (0%)
    Coronary artery disease 1/441 (0.2%) 0/223 (0%)
    Myocardial ischaemia 1/441 (0.2%) 0/223 (0%)
    Pericardial cyst 1/441 (0.2%) 0/223 (0%)
    Pericarditis 1/441 (0.2%) 0/223 (0%)
    Pulseless electrical activity 1/441 (0.2%) 0/223 (0%)
    Tachycardia 1/441 (0.2%) 0/223 (0%)
    Ear and labyrinth disorders
    Vertigo 4/441 (0.9%) 1/223 (0.4%)
    Endocrine disorders
    Adrenal mass 1/441 (0.2%) 0/223 (0%)
    Hypothyroidism 1/441 (0.2%) 0/223 (0%)
    Eye disorders
    Blindness unilateral 0/441 (0%) 1/223 (0.4%)
    Eye haemorrhage 1/441 (0.2%) 0/223 (0%)
    Glaucoma 1/441 (0.2%) 0/223 (0%)
    Retinal detachment 1/441 (0.2%) 0/223 (0%)
    Vision blurred 1/441 (0.2%) 0/223 (0%)
    Vitreous haemorrhage 0/441 (0%) 1/223 (0.4%)
    Gastrointestinal disorders
    Nausea 3/441 (0.7%) 0/223 (0%)
    Abdominal pain upper 0/441 (0%) 2/223 (0.9%)
    Abdominal pain lower 0/441 (0%) 1/223 (0.4%)
    Ascites 0/441 (0%) 1/223 (0.4%)
    Diverticulum intestinal haemorrhagic 0/441 (0%) 1/223 (0.4%)
    Gastric ulcer 1/441 (0.2%) 0/223 (0%)
    Gastrointestinal haemorrhage 0/441 (0%) 1/223 (0.4%)
    Hiatus hernia 0/441 (0%) 1/223 (0.4%)
    Inguinal hernia 1/441 (0.2%) 0/223 (0%)
    Pancreatitis 1/441 (0.2%) 0/223 (0%)
    Umbilical hernia 1/441 (0.2%) 0/223 (0%)
    Vomiting 1/441 (0.2%) 0/223 (0%)
    General disorders
    Non-cardiac chest pain 3/441 (0.7%) 1/223 (0.4%)
    Fatigue 2/441 (0.5%) 1/223 (0.4%)
    Adverse drug reaction 1/441 (0.2%) 0/223 (0%)
    Chest discomfort 1/441 (0.2%) 0/223 (0%)
    Chest pain 1/441 (0.2%) 0/223 (0%)
    Complication of device removal 1/441 (0.2%) 0/223 (0%)
    Puncture site haemorrhage 1/441 (0.2%) 0/223 (0%)
    Hepatobiliary disorders
    Cholecystitis 1/441 (0.2%) 1/223 (0.4%)
    Cholelithiasis 0/441 (0%) 2/223 (0.9%)
    Biliary colic 1/441 (0.2%) 0/223 (0%)
    Liver disorder 0/441 (0%) 1/223 (0.4%)
    Infections and infestations
    Appendicitis 2/441 (0.5%) 1/223 (0.4%)
    Pneumonia 1/441 (0.2%) 2/223 (0.9%)
    Campylobacter infection 1/441 (0.2%) 0/223 (0%)
    Chronic tonsillitis 0/441 (0%) 1/223 (0.4%)
    Cystitis 1/441 (0.2%) 0/223 (0%)
    Ear infection 0/441 (0%) 1/223 (0.4%)
    Empyema 1/441 (0.2%) 0/223 (0%)
    Gastroenteritis 1/441 (0.2%) 0/223 (0%)
    Gastrointestinal infection 1/441 (0.2%) 0/223 (0%)
    Influenza 0/441 (0%) 1/223 (0.4%)
    Malaria 1/441 (0.2%) 0/223 (0%)
    Renal abscess 0/441 (0%) 1/223 (0.4%)
    Staphylococcal skin infection 1/441 (0.2%) 0/223 (0%)
    Streptococcal infection 0/441 (0%) 1/223 (0.4%)
    Urosepsis 0/441 (0%) 1/223 (0.4%)
    Viral pericarditis 0/441 (0%) 1/223 (0.4%)
    Injury, poisoning and procedural complications
    Meniscus injury 0/441 (0%) 2/223 (0.9%)
    Wrist fracture 2/441 (0.5%) 0/223 (0%)
    Ankle fracture 1/441 (0.2%) 0/223 (0%)
    Cartilage injury 0/441 (0%) 1/223 (0.4%)
    Clavicle fracture 1/441 (0.2%) 0/223 (0%)
    Face injury 1/441 (0.2%) 0/223 (0%)
    Facial bones fracture 1/441 (0.2%) 0/223 (0%)
    Fall 1/441 (0.2%) 0/223 (0%)
    Foot fracture 1/441 (0.2%) 0/223 (0%)
    Head injury 1/441 (0.2%) 0/223 (0%)
    Incision site complication 1/441 (0.2%) 0/223 (0%)
    Incision site haematoma 1/441 (0.2%) 0/223 (0%)
    Incision site haemorrhage 1/441 (0.2%) 0/223 (0%)
    Joint dislocation 0/441 (0%) 1/223 (0.4%)
    Patella fracture 1/441 (0.2%) 0/223 (0%)
    Pelvic fracture 0/441 (0%) 1/223 (0.4%)
    Post procedural haemorrhage 1/441 (0.2%) 0/223 (0%)
    Postoperative fever 1/441 (0.2%) 0/223 (0%)
    Tendon rupture 1/441 (0.2%) 0/223 (0%)
    Tibia fracture 0/441 (0%) 1/223 (0.4%)
    Metabolism and nutrition disorders
    Obesity 1/441 (0.2%) 1/223 (0.4%)
    Hyponatraemia 1/441 (0.2%) 0/223 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/441 (0%) 2/223 (0.9%)
    Intervertebral disc protrusion 2/441 (0.5%) 0/223 (0%)
    Myalgia 2/441 (0.5%) 0/223 (0%)
    Arthritis 0/441 (0%) 1/223 (0.4%)
    Compartment syndrome 1/441 (0.2%) 0/223 (0%)
    Musculoskeletal pain 1/441 (0.2%) 0/223 (0%)
    Neck mass 1/441 (0.2%) 0/223 (0%)
    Neck pain 1/441 (0.2%) 0/223 (0%)
    Osteoarthritis 1/441 (0.2%) 0/223 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine leiomyoma 0/441 (0%) 2/223 (0.9%)
    Breast cancer 0/441 (0%) 1/223 (0.4%)
    Chronic lymphocytic leukaemia 1/441 (0.2%) 0/223 (0%)
    Parathyroid tumour benign 0/441 (0%) 1/223 (0.4%)
    Prostate cancer 1/441 (0.2%) 0/223 (0%)
    Thyroid cancer 1/441 (0.2%) 0/223 (0%)
    Nervous system disorders
    Headache 6/441 (1.4%) 4/223 (1.8%)
    Cerebrovascular accident 4/441 (0.9%) 5/223 (2.2%)
    Transient ischaemic attack 4/441 (0.9%) 5/223 (2.2%)
    Dizziness 4/441 (0.9%) 4/223 (1.8%)
    Dysaesthesia 6/441 (1.4%) 2/223 (0.9%)
    Migraine with aura 5/441 (1.1%) 3/223 (1.3%)
    Syncope 2/441 (0.5%) 4/223 (1.8%)
    Paraesthesia 2/441 (0.5%) 2/223 (0.9%)
    Migraine 2/441 (0.5%) 1/223 (0.4%)
    Carotid artery dissection 1/441 (0.2%) 1/223 (0.4%)
    Cerebral infarction 1/441 (0.2%) 1/223 (0.4%)
    Dysarthria 1/441 (0.2%) 1/223 (0.4%)
    Hemiparesis 2/441 (0.5%) 0/223 (0%)
    Monoparesis 1/441 (0.2%) 1/223 (0.4%)
    Aphasia 1/441 (0.2%) 0/223 (0%)
    Diabetic hyperosmolar coma 0/441 (0%) 1/223 (0.4%)
    Dural arteriovenous fistula 0/441 (0%) 1/223 (0.4%)
    Ischaemic stroke 1/441 (0.2%) 0/223 (0%)
    Lacunar infarction 0/441 (0%) 1/223 (0.4%)
    Nystagmus 0/441 (0%) 1/223 (0.4%)
    Partial seizures 1/441 (0.2%) 0/223 (0%)
    Sciatica 1/441 (0.2%) 0/223 (0%)
    Seizure 0/441 (0%) 1/223 (0.4%)
    Tension headache 0/441 (0%) 1/223 (0.4%)
    Thunderclap headache 1/441 (0.2%) 0/223 (0%)
    Tremor 0/441 (0%) 1/223 (0.4%)
    Ulnar tunnel syndrome 0/441 (0%) 1/223 (0.4%)
    Vertebral artery dissection 1/441 (0.2%) 0/223 (0%)
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous 1/441 (0.2%) 0/223 (0%)
    Product Issues
    Device dislocation 3/441 (0.7%) 0/223 (0%)
    Thrombosis in device 2/441 (0.5%) 0/223 (0%)
    Psychiatric disorders
    Depression 2/441 (0.5%) 1/223 (0.4%)
    Anxiety 1/441 (0.2%) 1/223 (0.4%)
    Psychotic disorder 0/441 (0%) 2/223 (0.9%)
    Bipolar disorder 1/441 (0.2%) 0/223 (0%)
    Completed suicide 1/441 (0.2%) 0/223 (0%)
    Conversion disorder 0/441 (0%) 1/223 (0.4%)
    Delusion 0/441 (0%) 1/223 (0.4%)
    Major depression 1/441 (0.2%) 0/223 (0%)
    Mania 1/441 (0.2%) 0/223 (0%)
    Mental status changes 0/441 (0%) 1/223 (0.4%)
    Paranoia 1/441 (0.2%) 0/223 (0%)
    Schizoaffective disorder 1/441 (0.2%) 0/223 (0%)
    Suicidal ideation 1/441 (0.2%) 0/223 (0%)
    Renal and urinary disorders
    Nephrolithiasis 3/441 (0.7%) 0/223 (0%)
    Calculus urethral 0/441 (0%) 1/223 (0.4%)
    Urethral meatus stenosis 1/441 (0.2%) 0/223 (0%)
    Reproductive system and breast disorders
    Menorrhagia 0/441 (0%) 2/223 (0.9%)
    Dysfunctional uterine bleeding 1/441 (0.2%) 0/223 (0%)
    Ovarian cyst 0/441 (0%) 1/223 (0.4%)
    Ovarian cyst ruptured 1/441 (0.2%) 0/223 (0%)
    Uterine haemorrhage 0/441 (0%) 1/223 (0.4%)
    Uterine prolapse 1/441 (0.2%) 0/223 (0%)
    Vaginal haemorrhage 1/441 (0.2%) 0/223 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism 2/441 (0.5%) 1/223 (0.4%)
    Pleural effusion 1/441 (0.2%) 1/223 (0.4%)
    Dyspnoea 0/441 (0%) 1/223 (0.4%)
    Respiratory arrest 1/441 (0.2%) 0/223 (0%)
    Sleep apnoea syndrome 1/441 (0.2%) 0/223 (0%)
    Surgical and medical procedures
    Osteosynthesis 1/441 (0.2%) 0/223 (0%)
    Vascular disorders
    Deep vein thrombosis 0/441 (0%) 2/223 (0.9%)
    Hypotension 2/441 (0.5%) 0/223 (0%)
    Aortic dissection 1/441 (0.2%) 0/223 (0%)
    Arteriovenous fistula 1/441 (0.2%) 0/223 (0%)
    Haematoma 1/441 (0.2%) 0/223 (0%)
    Hypertension 1/441 (0.2%) 0/223 (0%)
    Orthostatic hypotension 0/441 (0%) 1/223 (0.4%)
    Peripheral embolism 0/441 (0%) 1/223 (0.4%)
    Vena cava thrombosis 1/441 (0.2%) 0/223 (0%)
    Other (Not Including Serious) Adverse Events
    Device Closure Medical Management
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 324/441 (73.5%) 154/223 (69.1%)
    Blood and lymphatic system disorders
    Anaemia 2/441 (0.5%) 2/223 (0.9%)
    Lymphadenopathy 1/441 (0.2%) 1/223 (0.4%)
    Increased tendency to bruise 1/441 (0.2%) 0/223 (0%)
    Lymphocytosis 1/441 (0.2%) 0/223 (0%)
    Cardiac disorders
    Palpitations 64/441 (14.5%) 14/223 (6.3%)
    Atrial fibrillation 21/441 (4.8%) 0/223 (0%)
    Tachycardia 10/441 (2.3%) 1/223 (0.4%)
    Angina pectoris 3/441 (0.7%) 1/223 (0.4%)
    Sinus tachycardia 2/441 (0.5%) 1/223 (0.4%)
    Supraventricular extrasystoles 2/441 (0.5%) 1/223 (0.4%)
    Ventricular extrasystoles 3/441 (0.7%) 0/223 (0%)
    Atrial flutter 1/441 (0.2%) 0/223 (0%)
    Bradycardia 0/441 (0%) 1/223 (0.4%)
    Extrasystoles 2/441 (0.5%) 0/223 (0%)
    Myocardial ischaemia 1/441 (0.2%) 0/223 (0%)
    Arrhythmia 1/441 (0.2%) 0/223 (0%)
    Arrhythmia supraventricular 1/441 (0.2%) 0/223 (0%)
    Atrial thrombosis 1/441 (0.2%) 0/223 (0%)
    Atrioventricular block first degree 1/441 (0.2%) 0/223 (0%)
    Cardiac discomfort 1/441 (0.2%) 0/223 (0%)
    Postural orthostatic tachycardia syndrome 0/441 (0%) 1/223 (0.4%)
    Sinus node dysfunction 1/441 (0.2%) 0/223 (0%)
    Ventricular tachycardia 0/441 (0%) 1/223 (0.4%)
    Congenital, familial and genetic disorders
    Arteriovenous malformation 1/441 (0.2%) 0/223 (0%)
    Developmental hip dysplasia 1/441 (0.2%) 0/223 (0%)
    Pulmonary arteriovenous fistula 1/441 (0.2%) 0/223 (0%)
    Ear and labyrinth disorders
    Vertigo 8/441 (1.8%) 4/223 (1.8%)
    Tinnitus 6/441 (1.4%) 2/223 (0.9%)
    Ear pain 2/441 (0.5%) 2/223 (0.9%)
    Vertigo positional 4/441 (0.9%) 0/223 (0%)
    Deafness unilateral 1/441 (0.2%) 1/223 (0.4%)
    Tympanic membrane perforation 2/441 (0.5%) 0/223 (0%)
    Cerumen impaction 1/441 (0.2%) 0/223 (0%)
    Cupulolithiasis 1/441 (0.2%) 0/223 (0%)
    Deafness neurosensory 1/441 (0.2%) 0/223 (0%)
    Eustachian tube disorder 0/441 (0%) 1/223 (0.4%)
    Eustachian tube dysfunction 1/441 (0.2%) 0/223 (0%)
    Tympanic membrane hyperaemia 1/441 (0.2%) 0/223 (0%)
    Endocrine disorders
    Hypothyroidism 4/441 (0.9%) 1/223 (0.4%)
    Thyroid mass 1/441 (0.2%) 2/223 (0.9%)
    Eye disorders
    Visual impairment 8/441 (1.8%) 3/223 (1.3%)
    Vision blurred 4/441 (0.9%) 4/223 (1.8%)
    Diplopia 1/441 (0.2%) 2/223 (0.9%)
    Blindness transient 1/441 (0.2%) 1/223 (0.4%)
    Cataract 2/441 (0.5%) 0/223 (0%)
    Conjunctival haemorrhage 2/441 (0.5%) 0/223 (0%)
    Eye haemorrhage 1/441 (0.2%) 0/223 (0%)
    Mydriasis 1/441 (0.2%) 1/223 (0.4%)
    Photopsia 1/441 (0.2%) 1/223 (0.4%)
    Abnormal sensation in eye 0/441 (0%) 1/223 (0.4%)
    Blepharospasm 0/441 (0%) 1/223 (0.4%)
    Blindness 1/441 (0.2%) 0/223 (0%)
    Dry eye 1/441 (0.2%) 0/223 (0%)
    Eye pain 1/441 (0.2%) 0/223 (0%)
    Eyelid ptosis 0/441 (0%) 1/223 (0.4%)
    Iridocyclitis 1/441 (0.2%) 0/223 (0%)
    Iritis 1/441 (0.2%) 0/223 (0%)
    Keratitis 1/441 (0.2%) 0/223 (0%)
    Lens disorder 1/441 (0.2%) 0/223 (0%)
    Ocular discomfort 1/441 (0.2%) 0/223 (0%)
    Ocular hyperaemia 1/441 (0.2%) 0/223 (0%)
    Retinal artery occlusion 0/441 (0%) 1/223 (0.4%)
    Scleritis 1/441 (0.2%) 0/223 (0%)
    Gastrointestinal disorders
    Nausea 14/441 (3.2%) 7/223 (3.1%)
    Abdominal pain upper 4/441 (0.9%) 2/223 (0.9%)
    Gastrooesophageal reflux disease 6/441 (1.4%) 2/223 (0.9%)
    Constipation 5/441 (1.1%) 2/223 (0.9%)
    Diarrhoea 5/441 (1.1%) 2/223 (0.9%)
    Abdominal pain 4/441 (0.9%) 2/223 (0.9%)
    Gastritis 3/441 (0.7%) 2/223 (0.9%)
    Vomiting 3/441 (0.7%) 1/223 (0.4%)
    Dyspepsia 3/441 (0.7%) 1/223 (0.4%)
    Haematochezia 2/441 (0.5%) 2/223 (0.9%)
    Inguinal hernia 2/441 (0.5%) 1/223 (0.4%)
    Gastric ulcer 1/441 (0.2%) 1/223 (0.4%)
    Haemorrhoids 2/441 (0.5%) 1/223 (0.4%)
    Hiatus hernia 2/441 (0.5%) 0/223 (0%)
    Abdominal distension 2/441 (0.5%) 0/223 (0%)
    Abdominal pain lower 1/441 (0.2%) 0/223 (0%)
    Epigastric discomfort 1/441 (0.2%) 1/223 (0.4%)
    Haemorrhoidal haemorrhage 2/441 (0.5%) 0/223 (0%)
    Large intestine polyp 2/441 (0.5%) 0/223 (0%)
    Pancreatitis 1/441 (0.2%) 0/223 (0%)
    Abdominal discomfort 1/441 (0.2%) 0/223 (0%)
    Abdominal wall cyst 1/441 (0.2%) 0/223 (0%)
    Anal haemorrhage 1/441 (0.2%) 0/223 (0%)
    Change of bowel habit 1/441 (0.2%) 0/223 (0%)
    Colitis microscopic 1/441 (0.2%) 0/223 (0%)
    Diverticulum 1/441 (0.2%) 0/223 (0%)
    Dysphagia 1/441 (0.2%) 0/223 (0%)
    Eructation 0/441 (0%) 1/223 (0.4%)
    Gastrointestinal disorder 1/441 (0.2%) 0/223 (0%)
    Gingival bleeding 1/441 (0.2%) 0/223 (0%)
    Lower gastrointestinal haemorrhage 1/441 (0.2%) 0/223 (0%)
    Oesophageal obstruction 1/441 (0.2%) 0/223 (0%)
    Oesophageal pain 1/441 (0.2%) 0/223 (0%)
    Oral dysaesthesia 0/441 (0%) 1/223 (0.4%)
    Peptic ulcer 0/441 (0%) 1/223 (0.4%)
    Pharyngo-oesophageal diverticulum 1/441 (0.2%) 0/223 (0%)
    Rectal fissure 0/441 (0%) 1/223 (0.4%)
    Stomatitis 1/441 (0.2%) 0/223 (0%)
    Toothache 1/441 (0.2%) 0/223 (0%)
    General disorders
    Non-cardiac chest pain 23/441 (5.2%) 11/223 (4.9%)
    Fatigue 13/441 (2.9%) 9/223 (4%)
    Chest discomfort 11/441 (2.5%) 2/223 (0.9%)
    Oedema peripheral 10/441 (2.3%) 0/223 (0%)
    Chest pain 4/441 (0.9%) 2/223 (0.9%)
    Peripheral swelling 3/441 (0.7%) 3/223 (1.3%)
    Adverse drug reaction 3/441 (0.7%) 0/223 (0%)
    Pyrexia 2/441 (0.5%) 1/223 (0.4%)
    Influenza like illness 1/441 (0.2%) 1/223 (0.4%)
    Oedema 1/441 (0.2%) 1/223 (0.4%)
    Puncture site haemorrhage 1/441 (0.2%) 0/223 (0%)
    Drug withdrawal syndrome 1/441 (0.2%) 0/223 (0%)
    Feeling abnormal 1/441 (0.2%) 0/223 (0%)
    Feeling hot 0/441 (0%) 1/223 (0.4%)
    Gait disturbance 1/441 (0.2%) 0/223 (0%)
    Hernia 1/441 (0.2%) 0/223 (0%)
    Malaise 0/441 (0%) 1/223 (0.4%)
    Pain 1/441 (0.2%) 0/223 (0%)
    Puncture site pain 1/441 (0.2%) 0/223 (0%)
    Suprapubic pain 0/441 (0%) 1/223 (0.4%)
    Temperature intolerance 0/441 (0%) 1/223 (0.4%)
    Thirst 0/441 (0%) 1/223 (0.4%)
    Vessel puncture site bruise 1/441 (0.2%) 0/223 (0%)
    Vessel puncture site haemorrhage 1/441 (0.2%) 0/223 (0%)
    Hepatobiliary disorders
    Cholelithiasis 0/441 (0%) 1/223 (0.4%)
    Hepatic steatosis 2/441 (0.5%) 0/223 (0%)
    Hypertransaminasaemia 0/441 (0%) 1/223 (0.4%)
    Jaundice 0/441 (0%) 1/223 (0.4%)
    Immune system disorders
    Drug hypersensitivity 2/441 (0.5%) 0/223 (0%)
    Seasonal allergy 1/441 (0.2%) 1/223 (0.4%)
    Hypersensitivity 0/441 (0%) 1/223 (0.4%)
    Infections and infestations
    Upper respiratory tract infection 23/441 (5.2%) 4/223 (1.8%)
    Sinusitis 13/441 (2.9%) 6/223 (2.7%)
    Bronchitis 11/441 (2.5%) 3/223 (1.3%)
    Urinary tract infection 12/441 (2.7%) 2/223 (0.9%)
    Influenza 11/441 (2.5%) 1/223 (0.4%)
    Nasopharyngitis 8/441 (1.8%) 4/223 (1.8%)
    Pneumonia 5/441 (1.1%) 2/223 (0.9%)
    Acute sinusitis 3/441 (0.7%) 2/223 (0.9%)
    Pharyngitis 4/441 (0.9%) 1/223 (0.4%)
    Herpes zoster 3/441 (0.7%) 1/223 (0.4%)
    Skin infection 1/441 (0.2%) 3/223 (1.3%)
    Chronic tonsillitis 2/441 (0.5%) 0/223 (0%)
    Cystitis 2/441 (0.5%) 0/223 (0%)
    Ear infection 1/441 (0.2%) 1/223 (0.4%)
    Gastroenteritis 1/441 (0.2%) 1/223 (0.4%)
    Onychomycosis 2/441 (0.5%) 1/223 (0.4%)
    Otitis media 3/441 (0.7%) 0/223 (0%)
    Cellulitis 2/441 (0.5%) 0/223 (0%)
    Diverticulitis 1/441 (0.2%) 1/223 (0.4%)
    Epididymitis 1/441 (0.2%) 1/223 (0.4%)
    Folliculitis 1/441 (0.2%) 1/223 (0.4%)
    Otitis externa 2/441 (0.5%) 0/223 (0%)
    Otitis media acute 2/441 (0.5%) 0/223 (0%)
    Pharyngitis streptococcal 1/441 (0.2%) 1/223 (0.4%)
    Pyelonephritis 2/441 (0.5%) 0/223 (0%)
    Subcutaneous abscess 2/441 (0.5%) 0/223 (0%)
    Tinea pedis 2/441 (0.5%) 0/223 (0%)
    Tooth infection 2/441 (0.5%) 0/223 (0%)
    Vaginal infection 2/441 (0.5%) 0/223 (0%)
    Viral labyrinthitis 1/441 (0.2%) 1/223 (0.4%)
    Abscess limb 1/441 (0.2%) 0/223 (0%)
    Atypical pneumonia 1/441 (0.2%) 0/223 (0%)
    Chronic sinusitis 0/441 (0%) 1/223 (0.4%)
    Conjunctivitis 1/441 (0.2%) 0/223 (0%)
    Cytomegalovirus infection 0/441 (0%) 1/223 (0.4%)
    Epstein-Barr virus infection 0/441 (0%) 1/223 (0.4%)
    Erysipelas 0/441 (0%) 1/223 (0.4%)
    Eye infection 0/441 (0%) 1/223 (0.4%)
    Gastroenteritis salmonella 0/441 (0%) 1/223 (0.4%)
    Groin infection 1/441 (0.2%) 0/223 (0%)
    Helicobacter infection 0/441 (0%) 1/223 (0.4%)
    Herpes simplex 0/441 (0%) 1/223 (0.4%)
    Hordeolum 1/441 (0.2%) 0/223 (0%)
    Impetigo 1/441 (0.2%) 0/223 (0%)
    Infectious mononucleosis 0/441 (0%) 1/223 (0.4%)
    Labyrinthitis 0/441 (0%) 1/223 (0.4%)
    Laryngitis 0/441 (0%) 1/223 (0.4%)
    Localised infection 0/441 (0%) 1/223 (0.4%)
    Oral viral infection 1/441 (0.2%) 0/223 (0%)
    Otitis media chronic 0/441 (0%) 1/223 (0.4%)
    Paronychia 0/441 (0%) 1/223 (0.4%)
    Perichondritis 0/441 (0%) 1/223 (0.4%)
    Pilonidal cyst 1/441 (0.2%) 0/223 (0%)
    Rash pustular 1/441 (0.2%) 0/223 (0%)
    Respiratory tract infection 1/441 (0.2%) 0/223 (0%)
    Tinea cruris 1/441 (0.2%) 0/223 (0%)
    Tonsillitis 1/441 (0.2%) 0/223 (0%)
    Vestibular neuronitis 0/441 (0%) 1/223 (0.4%)
    Viral infection 1/441 (0.2%) 0/223 (0%)
    Viral upper respiratory tract infection 1/441 (0.2%) 0/223 (0%)
    Wound infection 1/441 (0.2%) 0/223 (0%)
    Injury, poisoning and procedural complications
    Contusion 11/441 (2.5%) 2/223 (0.9%)
    Incision site pain 9/441 (2%) 0/223 (0%)
    Laceration 5/441 (1.1%) 3/223 (1.3%)
    Ligament sprain 6/441 (1.4%) 2/223 (0.9%)
    Post procedural haemorrhage 6/441 (1.4%) 0/223 (0%)
    Arthropod bite 4/441 (0.9%) 2/223 (0.9%)
    Incision site haematoma 5/441 (1.1%) 0/223 (0%)
    Incision site haemorrhage 5/441 (1.1%) 0/223 (0%)
    Foot fracture 4/441 (0.9%) 0/223 (0%)
    Incision site complication 3/441 (0.7%) 0/223 (0%)
    Limb injury 4/441 (0.9%) 0/223 (0%)
    Meniscus injury 1/441 (0.2%) 1/223 (0.4%)
    Wrist fracture 2/441 (0.5%) 0/223 (0%)
    Fall 2/441 (0.5%) 0/223 (0%)
    Hand fracture 1/441 (0.2%) 2/223 (0.9%)
    Procedural complication 3/441 (0.7%) 0/223 (0%)
    Procedural pain 3/441 (0.7%) 0/223 (0%)
    Road traffic accident 3/441 (0.7%) 0/223 (0%)
    Tendon rupture 1/441 (0.2%) 1/223 (0.4%)
    Ankle fracture 0/441 (0%) 1/223 (0.4%)
    Burns second degree 2/441 (0.5%) 0/223 (0%)
    Cartilage injury 1/441 (0.2%) 0/223 (0%)
    Concussion 2/441 (0.5%) 0/223 (0%)
    Epicondylitis 2/441 (0.5%) 0/223 (0%)
    Facial bones fracture 1/441 (0.2%) 0/223 (0%)
    Injury 1/441 (0.2%) 1/223 (0.4%)
    Joint dislocation 1/441 (0.2%) 0/223 (0%)
    Muscle strain 1/441 (0.2%) 1/223 (0.4%)
    Rib fracture 1/441 (0.2%) 1/223 (0.4%)
    Alcohol poisoning 0/441 (0%) 1/223 (0.4%)
    Anaemia postoperative 0/441 (0%) 1/223 (0.4%)
    Animal scratch 1/441 (0.2%) 0/223 (0%)
    Arthropod sting 0/441 (0%) 1/223 (0.4%)
    Chest injury 1/441 (0.2%) 0/223 (0%)
    Craniocerebral injury 1/441 (0.2%) 0/223 (0%)
    Endotracheal intubation complication 1/441 (0.2%) 0/223 (0%)
    Exposure to body fluid 1/441 (0.2%) 0/223 (0%)
    Face injury 1/441 (0.2%) 0/223 (0%)
    Femur fracture 0/441 (0%) 1/223 (0.4%)
    Fibula fracture 0/441 (0%) 1/223 (0.4%)
    Ligament rupture 1/441 (0.2%) 0/223 (0%)
    Limb traumatic amputation 0/441 (0%) 1/223 (0.4%)
    Persistent corneal epithelial defect 1/441 (0.2%) 0/223 (0%)
    Post-traumatic neck syndrome 1/441 (0.2%) 0/223 (0%)
    Procedural headache 1/441 (0.2%) 0/223 (0%)
    Procedural hypotension 0/441 (0%) 1/223 (0.4%)
    Radius fracture 1/441 (0.2%) 0/223 (0%)
    Scapula fracture 0/441 (0%) 1/223 (0.4%)
    Skin abrasion 1/441 (0.2%) 0/223 (0%)
    Subcutaneous haematoma 0/441 (0%) 1/223 (0.4%)
    Traumatic haematoma 1/441 (0.2%) 0/223 (0%)
    Upper limb fracture 1/441 (0.2%) 0/223 (0%)
    Wound complication 1/441 (0.2%) 0/223 (0%)
    Investigations
    Weight decreased 2/441 (0.5%) 0/223 (0%)
    Weight increased 1/441 (0.2%) 1/223 (0.4%)
    Blood magnesium decreased 1/441 (0.2%) 0/223 (0%)
    Grip strength decreased 0/441 (0%) 1/223 (0.4%)
    Heart rate irregular 1/441 (0.2%) 0/223 (0%)
    Platelet count increased 1/441 (0.2%) 0/223 (0%)
    Prostatic specific antigen abnormal 1/441 (0.2%) 0/223 (0%)
    Metabolism and nutrition disorders
    Hypokalaemia 5/441 (1.1%) 0/223 (0%)
    Hypercholesterolaemia 2/441 (0.5%) 2/223 (0.9%)
    Dehydration 2/441 (0.5%) 1/223 (0.4%)
    Iron deficiency 1/441 (0.2%) 2/223 (0.9%)
    Glucose tolerance impaired 1/441 (0.2%) 1/223 (0.4%)
    Hyperlipidaemia 1/441 (0.2%) 1/223 (0.4%)
    Hypoglycaemia 2/441 (0.5%) 0/223 (0%)
    Hyponatraemia 0/441 (0%) 1/223 (0.4%)
    Vitamin D deficiency 2/441 (0.5%) 0/223 (0%)
    Abnormal loss of weight 1/441 (0.2%) 0/223 (0%)
    Abnormal weight gain 0/441 (0%) 1/223 (0.4%)
    Decreased appetite 0/441 (0%) 1/223 (0.4%)
    Diabetes mellitus 1/441 (0.2%) 0/223 (0%)
    Dyslipidaemia 0/441 (0%) 1/223 (0.4%)
    Gout 0/441 (0%) 1/223 (0.4%)
    Hyperglycaemia 0/441 (0%) 1/223 (0.4%)
    Hyperhomocysteinaemia 0/441 (0%) 1/223 (0.4%)
    Hypertriglyceridaemia 1/441 (0.2%) 0/223 (0%)
    Hypocalcaemia 0/441 (0%) 1/223 (0.4%)
    Hypomagnesaemia 1/441 (0.2%) 0/223 (0%)
    Postprandial hypoglycaemia 1/441 (0.2%) 0/223 (0%)
    Type 2 diabetes mellitus 0/441 (0%) 1/223 (0.4%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 19/441 (4.3%) 9/223 (4%)
    Back pain 18/441 (4.1%) 8/223 (3.6%)
    Pain in extremity 18/441 (4.1%) 6/223 (2.7%)
    Myalgia 9/441 (2%) 5/223 (2.2%)
    Neck pain 3/441 (0.7%) 6/223 (2.7%)
    Musculoskeletal pain 4/441 (0.9%) 3/223 (1.3%)
    Muscle spasms 5/441 (1.1%) 2/223 (0.9%)
    Musculoskeletal chest pain 5/441 (1.1%) 1/223 (0.4%)
    Groin pain 5/441 (1.1%) 0/223 (0%)
    Intervertebral disc protrusion 3/441 (0.7%) 0/223 (0%)
    Osteoarthritis 3/441 (0.7%) 1/223 (0.4%)
    Rotator cuff syndrome 2/441 (0.5%) 2/223 (0.9%)
    Bursitis 3/441 (0.7%) 0/223 (0%)
    Limb discomfort 2/441 (0.5%) 1/223 (0.4%)
    Joint swelling 2/441 (0.5%) 0/223 (0%)
    Plantar fasciitis 2/441 (0.5%) 0/223 (0%)
    Synovial cyst 1/441 (0.2%) 1/223 (0.4%)
    Tendonitis 2/441 (0.5%) 0/223 (0%)
    Costochondritis 1/441 (0.2%) 0/223 (0%)
    Exostosis 1/441 (0.2%) 0/223 (0%)
    Fibromyalgia 1/441 (0.2%) 0/223 (0%)
    Flank pain 0/441 (0%) 1/223 (0.4%)
    Foot deformity 1/441 (0.2%) 0/223 (0%)
    Inguinal mass 1/441 (0.2%) 0/223 (0%)
    Intervertebral disc degeneration 1/441 (0.2%) 0/223 (0%)
    Jaw disorder 0/441 (0%) 1/223 (0.4%)
    Muscle haemorrhage 0/441 (0%) 1/223 (0.4%)
    Muscle tightness 1/441 (0.2%) 0/223 (0%)
    Muscular weakness 1/441 (0.2%) 0/223 (0%)
    Musculoskeletal discomfort 0/441 (0%) 1/223 (0.4%)
    Myalgia intercostal 1/441 (0.2%) 0/223 (0%)
    Myokymia 0/441 (0%) 1/223 (0.4%)
    Osteoporosis 1/441 (0.2%) 0/223 (0%)
    Pain in jaw 0/441 (0%) 1/223 (0.4%)
    Periarthritis 1/441 (0.2%) 0/223 (0%)
    Polymyalgia rheumatica 1/441 (0.2%) 0/223 (0%)
    Rheumatic disorder 1/441 (0.2%) 0/223 (0%)
    Rheumatoid arthritis 1/441 (0.2%) 0/223 (0%)
    Sjogren's syndrome 1/441 (0.2%) 0/223 (0%)
    Spinal osteoarthritis 1/441 (0.2%) 0/223 (0%)
    Synovitis 0/441 (0%) 1/223 (0.4%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Uterine leiomyoma 1/441 (0.2%) 0/223 (0%)
    Colon adenoma 2/441 (0.5%) 0/223 (0%)
    Acoustic neuroma 1/441 (0.2%) 0/223 (0%)
    Basal cell carcinoma 1/441 (0.2%) 0/223 (0%)
    Benign breast neoplasm 0/441 (0%) 1/223 (0.4%)
    Benign neoplasm of skin 1/441 (0.2%) 0/223 (0%)
    Bladder cancer 0/441 (0%) 1/223 (0.4%)
    Eye naevus 0/441 (0%) 1/223 (0.4%)
    Haemangioma of liver 0/441 (0%) 1/223 (0.4%)
    Lipoma 1/441 (0.2%) 0/223 (0%)
    Skin cancer 0/441 (0%) 1/223 (0.4%)
    Squamous cell carcinoma 1/441 (0.2%) 0/223 (0%)
    Squamous cell carcinoma of skin 0/441 (0%) 1/223 (0.4%)
    Nervous system disorders
    Headache 37/441 (8.4%) 32/223 (14.3%)
    Dizziness 34/441 (7.7%) 16/223 (7.2%)
    Dysaesthesia 19/441 (4.3%) 19/223 (8.5%)
    Migraine 15/441 (3.4%) 5/223 (2.2%)
    Migraine with aura 8/441 (1.8%) 4/223 (1.8%)
    Transient ischaemic attack 6/441 (1.4%) 5/223 (2.2%)
    Paraesthesia 10/441 (2.3%) 3/223 (1.3%)
    Cerebrovascular accident 1/441 (0.2%) 4/223 (1.8%)
    Syncope 5/441 (1.1%) 2/223 (0.9%)
    Memory impairment 5/441 (1.1%) 4/223 (1.8%)
    Dysarthria 3/441 (0.7%) 2/223 (0.9%)
    Monoparesis 3/441 (0.7%) 2/223 (0.9%)
    Presyncope 7/441 (1.6%) 0/223 (0%)
    Aphasia 1/441 (0.2%) 4/223 (1.8%)
    Hemiparesis 3/441 (0.7%) 1/223 (0.4%)
    Seizure 2/441 (0.5%) 2/223 (0.9%)
    Balance disorder 2/441 (0.5%) 2/223 (0.9%)
    Cervical radiculopathy 3/441 (0.7%) 1/223 (0.4%)
    Facial paralysis 2/441 (0.5%) 2/223 (0.9%)
    Visual field defect 2/441 (0.5%) 2/223 (0.9%)
    Amnesia 1/441 (0.2%) 2/223 (0.9%)
    Ataxia 1/441 (0.2%) 2/223 (0.9%)
    Cerebral infarction 1/441 (0.2%) 0/223 (0%)
    Disturbance in attention 1/441 (0.2%) 2/223 (0.9%)
    Hypoaesthesia 2/441 (0.5%) 1/223 (0.4%)
    Lumbar radiculopathy 1/441 (0.2%) 2/223 (0.9%)
    Sensory disturbance 2/441 (0.5%) 1/223 (0.4%)
    Tension headache 1/441 (0.2%) 1/223 (0.4%)
    Carpal tunnel syndrome 2/441 (0.5%) 0/223 (0%)
    Lacunar infarction 0/441 (0%) 1/223 (0.4%)
    Nerve compression 1/441 (0.2%) 1/223 (0.4%)
    Sciatica 0/441 (0%) 1/223 (0.4%)
    Sensory loss 2/441 (0.5%) 0/223 (0%)
    Tremor 1/441 (0.2%) 0/223 (0%)
    Amimia 1/441 (0.2%) 0/223 (0%)
    Aura 1/441 (0.2%) 0/223 (0%)
    Burning sensation 0/441 (0%) 1/223 (0.4%)
    Clumsiness 1/441 (0.2%) 0/223 (0%)
    Cognitive disorder 0/441 (0%) 1/223 (0.4%)
    Depressed level of consciousness 0/441 (0%) 1/223 (0.4%)
    Diabetic neuropathy 1/441 (0.2%) 0/223 (0%)
    Dizziness postural 1/441 (0.2%) 0/223 (0%)
    Encephalopathy 1/441 (0.2%) 0/223 (0%)
    Exertional headache 0/441 (0%) 1/223 (0.4%)
    Facial paresis 1/441 (0.2%) 0/223 (0%)
    Fine motor skill dysfunction 1/441 (0.2%) 0/223 (0%)
    Focal dyscognitive seizures 1/441 (0.2%) 0/223 (0%)
    Head discomfort 1/441 (0.2%) 0/223 (0%)
    Loss of consciousness 1/441 (0.2%) 0/223 (0%)
    Mental impairment 0/441 (0%) 1/223 (0.4%)
    Morton's neuralgia 1/441 (0.2%) 0/223 (0%)
    Muscle spasticity 0/441 (0%) 1/223 (0.4%)
    Neuropathy peripheral 0/441 (0%) 1/223 (0.4%)
    Nystagmus 0/441 (0%) 1/223 (0.4%)
    Occipital neuralgia 1/441 (0.2%) 0/223 (0%)
    Parkinson's disease 1/441 (0.2%) 0/223 (0%)
    Peroneal nerve palsy 0/441 (0%) 1/223 (0.4%)
    Pineal gland cyst 1/441 (0.2%) 0/223 (0%)
    Quadrantanopia 0/441 (0%) 1/223 (0.4%)
    Somnolence 0/441 (0%) 1/223 (0.4%)
    Speech disorder 1/441 (0.2%) 0/223 (0%)
    Subdural effusion 0/441 (0%) 1/223 (0.4%)
    Ulnar neuritis 0/441 (0%) 1/223 (0.4%)
    Upper motor neurone lesion 0/441 (0%) 1/223 (0.4%)
    Pregnancy, puerperium and perinatal conditions
    Gestational hypertension 1/441 (0.2%) 0/223 (0%)
    Psychiatric disorders
    Anxiety 17/441 (3.9%) 4/223 (1.8%)
    Depression 8/441 (1.8%) 8/223 (3.6%)
    Insomnia 8/441 (1.8%) 5/223 (2.2%)
    Post stroke depression 5/441 (1.1%) 2/223 (0.9%)
    Affect lability 3/441 (0.7%) 1/223 (0.4%)
    Confusional state 3/441 (0.7%) 1/223 (0.4%)
    Panic attack 2/441 (0.5%) 2/223 (0.9%)
    Sleep disorder 0/441 (0%) 4/223 (1.8%)
    Attention deficit/hyperactivity disorder 2/441 (0.5%) 0/223 (0%)
    Bipolar disorder 1/441 (0.2%) 0/223 (0%)
    Major depression 1/441 (0.2%) 0/223 (0%)
    Agitated depression 1/441 (0.2%) 0/223 (0%)
    Alcohol abuse 1/441 (0.2%) 0/223 (0%)
    Alcohol withdrawal syndrome 1/441 (0.2%) 0/223 (0%)
    Anxiety disorder 1/441 (0.2%) 0/223 (0%)
    Drug abuse 1/441 (0.2%) 0/223 (0%)
    Executive dysfunction 0/441 (0%) 1/223 (0.4%)
    Hallucination 1/441 (0.2%) 0/223 (0%)
    Mood altered 1/441 (0.2%) 0/223 (0%)
    Paranoia 1/441 (0.2%) 0/223 (0%)
    Post-traumatic stress disorder 1/441 (0.2%) 0/223 (0%)
    Somnambulism 0/441 (0%) 1/223 (0.4%)
    Stress 0/441 (0%) 1/223 (0.4%)
    Renal and urinary disorders
    Nephrolithiasis 6/441 (1.4%) 1/223 (0.4%)
    Dysuria 2/441 (0.5%) 0/223 (0%)
    Haematuria 1/441 (0.2%) 1/223 (0.4%)
    Stress urinary incontinence 2/441 (0.5%) 0/223 (0%)
    Urinary incontinence 1/441 (0.2%) 1/223 (0.4%)
    Haemorrhage urinary tract 1/441 (0.2%) 0/223 (0%)
    Renal failure 1/441 (0.2%) 0/223 (0%)
    Urethral stenosis 0/441 (0%) 1/223 (0.4%)
    Urine abnormality 1/441 (0.2%) 0/223 (0%)
    Reproductive system and breast disorders
    Menorrhagia 5/441 (1.1%) 2/223 (0.9%)
    Vaginal haemorrhage 1/441 (0.2%) 3/223 (1.3%)
    Breast pain 1/441 (0.2%) 1/223 (0.4%)
    Metrorrhagia 2/441 (0.5%) 0/223 (0%)
    Ovarian cyst 1/441 (0.2%) 0/223 (0%)
    Prostatitis 2/441 (0.5%) 0/223 (0%)
    Uterine prolapse 0/441 (0%) 1/223 (0.4%)
    Adnexa uteri mass 1/441 (0.2%) 0/223 (0%)
    Amenorrhoea 0/441 (0%) 1/223 (0.4%)
    Benign prostatic hyperplasia 0/441 (0%) 1/223 (0.4%)
    Breast mass 0/441 (0%) 1/223 (0.4%)
    Dysmenorrhoea 0/441 (0%) 1/223 (0.4%)
    Endometrial disorder 1/441 (0.2%) 0/223 (0%)
    Erectile dysfunction 1/441 (0.2%) 0/223 (0%)
    Menopausal symptoms 0/441 (0%) 1/223 (0.4%)
    Pelvic discomfort 1/441 (0.2%) 0/223 (0%)
    Polycystic ovaries 1/441 (0.2%) 0/223 (0%)
    Premenstrual dysphoric disorder 1/441 (0.2%) 0/223 (0%)
    Testicular mass 1/441 (0.2%) 0/223 (0%)
    Testicular pain 1/441 (0.2%) 0/223 (0%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 13/441 (2.9%) 6/223 (2.7%)
    Epistaxis 7/441 (1.6%) 5/223 (2.2%)
    Cough 7/441 (1.6%) 3/223 (1.3%)
    Sleep apnoea syndrome 5/441 (1.1%) 2/223 (0.9%)
    Oropharyngeal pain 5/441 (1.1%) 2/223 (0.9%)
    Dyspnoea exertional 4/441 (0.9%) 2/223 (0.9%)
    Pulmonary embolism 1/441 (0.2%) 0/223 (0%)
    Nasal congestion 2/441 (0.5%) 1/223 (0.4%)
    Pleural effusion 1/441 (0.2%) 0/223 (0%)
    Asthma 2/441 (0.5%) 0/223 (0%)
    Nasal septum deviation 2/441 (0.5%) 0/223 (0%)
    Pleurisy 1/441 (0.2%) 1/223 (0.4%)
    Pulmonary mass 0/441 (0%) 2/223 (0.9%)
    Sinus congestion 1/441 (0.2%) 1/223 (0.4%)
    Sinus disorder 1/441 (0.2%) 1/223 (0.4%)
    Asthma exercise induced 1/441 (0.2%) 0/223 (0%)
    Haemoptysis 0/441 (0%) 1/223 (0.4%)
    Hyperventilation 1/441 (0.2%) 0/223 (0%)
    Hypoxia 1/441 (0.2%) 0/223 (0%)
    Nasal polyps 1/441 (0.2%) 0/223 (0%)
    Nasal turbinate hypertrophy 1/441 (0.2%) 0/223 (0%)
    Paranasal sinus mucosal hypertrophy 1/441 (0.2%) 0/223 (0%)
    Productive cough 1/441 (0.2%) 0/223 (0%)
    Respiratory tract congestion 0/441 (0%) 1/223 (0.4%)
    Rhinorrhoea 1/441 (0.2%) 0/223 (0%)
    Sinus pain 0/441 (0%) 1/223 (0.4%)
    Wheezing 0/441 (0%) 1/223 (0.4%)
    Skin and subcutaneous tissue disorders
    Rash 3/441 (0.7%) 3/223 (1.3%)
    Alopecia 1/441 (0.2%) 2/223 (0.9%)
    Hyperhidrosis 2/441 (0.5%) 1/223 (0.4%)
    Pruritus 2/441 (0.5%) 1/223 (0.4%)
    Psoriasis 1/441 (0.2%) 1/223 (0.4%)
    Rosacea 2/441 (0.5%) 0/223 (0%)
    Swelling face 1/441 (0.2%) 1/223 (0.4%)
    Urticaria 1/441 (0.2%) 1/223 (0.4%)
    Acne 1/441 (0.2%) 0/223 (0%)
    Blister 1/441 (0.2%) 0/223 (0%)
    Chloasma 1/441 (0.2%) 0/223 (0%)
    Dermatitis 0/441 (0%) 1/223 (0.4%)
    Dermatitis allergic 1/441 (0.2%) 0/223 (0%)
    Dermatitis atopic 0/441 (0%) 1/223 (0.4%)
    Hand dermatitis 1/441 (0.2%) 0/223 (0%)
    Ingrowing nail 1/441 (0.2%) 0/223 (0%)
    Pemphigus 1/441 (0.2%) 0/223 (0%)
    Petechiae 0/441 (0%) 1/223 (0.4%)
    Precancerous skin lesion 0/441 (0%) 1/223 (0.4%)
    Pustular psoriasis 1/441 (0.2%) 0/223 (0%)
    Rash generalised 1/441 (0.2%) 0/223 (0%)
    Seborrhoeic dermatitis 1/441 (0.2%) 0/223 (0%)
    Skin depigmentation 1/441 (0.2%) 0/223 (0%)
    Skin irritation 1/441 (0.2%) 0/223 (0%)
    Skin lesion 1/441 (0.2%) 0/223 (0%)
    Stasis dermatitis 1/441 (0.2%) 0/223 (0%)
    Surgical and medical procedures
    Dental disorder prophylaxis 0/441 (0%) 1/223 (0.4%)
    Tooth extraction 0/441 (0%) 1/223 (0.4%)
    Vascular disorders
    Hypertension 21/441 (4.8%) 9/223 (4%)
    Hypotension 3/441 (0.7%) 0/223 (0%)
    Haematoma 3/441 (0.7%) 0/223 (0%)
    Flushing 2/441 (0.5%) 1/223 (0.4%)
    Orthostatic hypotension 1/441 (0.2%) 1/223 (0.4%)
    Varicose vein 3/441 (0.7%) 0/223 (0%)
    Essential hypertension 1/441 (0.2%) 1/223 (0.4%)
    Aortic aneurysm 0/441 (0%) 1/223 (0.4%)
    Hot flush 1/441 (0.2%) 0/223 (0%)
    Infarction 1/441 (0.2%) 0/223 (0%)
    Intermittent claudication 1/441 (0.2%) 0/223 (0%)
    Labile hypertension 0/441 (0%) 1/223 (0.4%)
    Peripheral embolism 0/441 (0%) 0/223 (0%)
    Phlebitis 1/441 (0.2%) 0/223 (0%)
    Thrombophlebitis 0/441 (0%) 1/223 (0.4%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    Publication of results requires review and approval by REDUCE Publication and Presentation Committee

    Results Point of Contact

    Name/Title Bryan Randall
    Organization W. L. Gore & Associates
    Phone 928-864-4832
    Email BRandall@WLGore.com
    Responsible Party:
    W.L.Gore & Associates
    ClinicalTrials.gov Identifier:
    NCT00738894
    Other Study ID Numbers:
    • HLX 06-03
    First Posted:
    Aug 21, 2008
    Last Update Posted:
    Nov 20, 2020
    Last Verified:
    Oct 1, 2020