Fracture REduction Evaluation (FREE) Study Efficacy and Safety of Balloon Kyphoplasty Compared with Non-surgical Care for Vertebral Compression Fracture (FREE): A Randomised Controlled Trial Wardlaw Lancet 2009 Balloon Kyphoplasty for the Treatment of Acute Vertebral Compression Fractures: 2 year Results from a Randomized Trial Boonen JBMR 2011 [speaker] [title] PMD006367-1.0 ClinicalTrials.gov NCT00211211
Level I Clinical Evidence Randomized Controlled Trial (RCT) Kyphon Balloon Kyphoplasty (BKP) vs. Non-surgical Management (NSM) Largest RCT for any vertebral augmentation procedure Multicenter, Multinational 21 European sites, 8 countries Large Cohort, Randomized n = 300 patients: 149 Balloon Kyphoplasty, 151 Non-surgical Management 24-month Follow-up 2-year results (f/u 1, 3, 6, 12, and 24 months) Multiple Validated Outcome Measures QOL, back function, activity days, back pain, analgesic usage, patient satisfaction Independent Statistical & Radiographic Assessment 2 PMD006367-1.0 FREE Study Outcomes
Inclusion/Exclusion Criteria Major Inclusion Criteria 1 to 3 VCFs between T5 - L5 At least one with edema on MRI At least one with 15% height loss Fractures due to osteoporosis (primary or secondary), multiple myeloma or osteolytic metastatic tumors Back pain score 4 on VAS (0-10) Major Exclusion Criteria Fractures 3 months old Previous vertebroplasty Neurological deficit Radicular pain Spinal cord compression Canal narrowing History of disabling back pain, not caused by VCFs Dementia Unable to walk prior to fracture 3 PMD006367-1.0 FREE Study Outcomes
Study Design Fracture 3 months 300 Patients Screening MRI Baseline Stratified for: Gender Etiology of fracture Bisphosphonate use Corticosteroid use Randomization Balloon Kyphoplasty (BKP) n = 149 Images: courtesy of Dr J Van Meirhaeghe 149 138 134 131 124 Start Treatment 5-10 days 1 month 3 month 6 month 12 month 151 128 117 115 111 120 24 month 112 Non-surgical Care (Control) n = 151 Treatment according to hospital protocol - Pain medication - Bed rest - Bracing - Physiotherapy - Rehabilitation programs - Walking aids 4 PMD006367-1.0 FREE Study Outcomes
Study Design: Endpoints Primary SF-36 PCS (Physical Component Summary) at 1 month (scale 0 100) Validated global QOL measure weighted on physical abilities Secondary Quality of Life (QOL) SF-36 subscales (scale 0 100) EuroQol-5D (EQ-5D) Questionnaire (scale 0 1) Back Function & Mobility Roland-Morris Disability (0 24) Restricted activity days and bed rest due to back pain in the past 2 weeks Back Pain: visual-analogue scale (0 10) Pain medication use (narcotics & opioids) Patient satisfaction (Likert Scale, 1 20) Device- & procedure-related safety Radiograph assessments and economic data collected but not reported in 12mo or 24mo publications 5 PMD006367-1.0 FREE Study Outcomes
Baseline Demographics & Characteristics BKP (n = 149) NSM (n = 151) Age: years Mean (SD) 72.2 (± 9.3) 74.1 (± 9.4) Age Range: years 44.5 95.2 52.8 89.1 Female n (%) 115 (77%) 117 (77%) Underlying cause of Fracture Primary Osteoporosis n (%) 145 (97%) 143 (95%) Secondary Osteoporosis (steroids) n (%) 2 (1.3%) 6 (4.0%) Multiple myeloma / metastatic n (%) 2 (1.3%) 2 (1.3%) Bisphosphonate use (at baseline) n (%) 49 (33%) 49 (32%) 12 months use n (%) 13 (9%) 16 (11%) Glucocorticoid use n (%) 26 (17%) 26 (17%) Baseline Fractures 1 n (%) 100 (67%) 115 (76%) 2 n (%) 34 (23%) 28 (19%) 3 n (%) 15 (10%)* 8 (5%) Baseline Fracture Location n = 214 n = 195 Thoracic (T5-T9) n (%) 49 (23%) 41 (21%) Thoracolumbar Junction (T10-L2) n (%) 127 (59%) 130 (67%) Lumbar (L3-L5) n (%) 38 (18%) 24 (12%) Groups similar at baseline with the exception of multiple fractures * One patient had a fourth index fracture identified between screening and planned surgery 6 PMD006367-1.0 FREE Study Outcomes
Baseline Demographics & Characteristics BKP NSM Fracture grade (Genant*) n = 149 n = 151 grade 2 (>25% deformity) (%) 63% 77% grade 3 (>40% deformity) (%) 27% 31% Hip T-score n = 122 n = 121 Normal ( -1.0) n (%) 30 (25%) 18 (15%) Osteopenic (< -1.0 to -2.5) n (%) 58 (48%) 61 (50%) Osteoporotic (< -2.5) n (%) 34 (28%) 42 (35%) Spine T-score n = 135 n = 128 Normal ( -1.0) n (%) 28 (21%) 20 (16%) Osteopenic (< -1.0 to -2.5) n (%) 54 (40%) 57 (45%) Osteoporotic (< -2.5) n (%) 53 (39%) 51 (40%) Groups similar at baseline. * Genant HK, et al. Vertebral Fracture Assessment Using a Semiquantitative Technique. J Bone Miner Res. 1993;8(9):1137-48. 7 PMD006367-1.0 FREE Study Outcomes
Group Means and 95% CI Primary Endpoint: SF-36 PCS at 1 Month SF-36 Physical Component Summary (PCS) Score Quality of life weighted on physical abilities 40 35 30 25 p=0.35 p<0.0001 p<0.0001 BKP treatment is superior to NSM when measured by SF-36 PCS (primary endpoint) Only BKP saw a statistical (p<0.0001) and clinical (>3.5 MCID) improvement 20 15 10 3.5 point change from baseline needed for clinical significance or MCID (Minimally Clinically Important Difference) Copay Spine J 2008 5 BKP 0 Baseline 1 Month NSM (control) 8 PMD006367-1.0 FREE Study Outcomes
Quality of Life SF-36 Physical component summary (PCS) score Quality of life weighted on physical abilities SF-36 PCS Score (mean and 95% CI) 100 50 40 30 20 10 0 p=0.001* p=0.096 p=0.13 Faster Improvement (Treatment x Visit p<0.0001) 0 6 12 18 24 Follow-up (Months) Treatment p=0.0001 BKP NSM (control) BKP provided: Better Treatment Effect Over 2 years On average 3.24 points greater across 24 mo Better Average Scores Statistically significantly* higher at 1, 3 and 6 mo Faster Improvement Statistically significantly greater efficacy at the early time points Near Return to Norm Swedish aged-matched norm PCS for females 75 years without VCF (~37) Sullivan SF-36 Hälsoenkät 2002 9 PMD006367-1.0 FREE Study Outcomes
Quality of Life EQ-5D (Global Health Outcome) Total EQ-5D (means and 95% CI) 1.0 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 p=0.002* p=0.0009* p=0.006* p=0.040* 0 6 12 18 24 Follow -up (m onths) Treatment p<0.0001 BKP NSM (control) BKP provided: Better Treatment Effect Over 2 years On average 0.12 points greater across 24 mo Better Average Scores Statistically significantly* higher at ALL time points BKP significantly better than NSM: Statistically higher QALY (Quality-Adjusted Life Years) in Year 1 (25.9%; p=0.007) and Year 2 (15.4%; p=0.029) 10 PMD006367-1.0 FREE Study Outcomes
Mobility Roland-Morris Score (mean and 95% CI) Roland Morris Disability Assessment of Back Function 24 20 16 12 8 4 0 Faster Improvement (Treatment x Visit ) Treatment p<0.0001 BKP p=0.059 NSM (control) 0 6 12 18 24 Follow-up (months) BKP provided: Better Treatment Effect Over 2 years On average -3.01 point difference across 24 mo Better Average Scores Statistically significantly* higher at 1, 3, 6 and 12 mo Faster Improvement Statistically significantly* greater efficacy at the early time points 11 PMD006367-1.0 FREE Study Outcomes
Reduced Activity (Days) (mean and 95% CI) Mobility Limited Activity Days 14 12 10 8 Faster Improvement (Treatment x Visit ) BKP NSM (control) Treatment p<0.0001 BKP provided: Better Treatment Effect Over 2 years On average -2.62-day difference over 24 mo Over 2 years, BKP patients had an estimated 136 more days (4.5 mo) of activity than NSM 6 4 2 0 p=0.0008* p=0.006* p=0.12 0 6 12 18 24 Follow-up (months) Better Average Scores Statistically significantly* higher at 1, 3, 6 and 12 mo Faster Improvement Statistically significantly* greater efficacy at the early time points Assessment of limited activity days (within 2 weeks) 12 PMD006367-1.0 FREE Study Outcomes
Pain Relief Back Pain & Bodily Pain BKP provided: Back Pain Score (mean and 95% CI) 10 8 7 6 5 4 3 2 p=0.001* BKP NSM (control) Treatment p<0.0001 p=0.006* Better Treatment Effect Over 2 years On average 1.49 points greater reduction over 24 mo Better Average Scores Statistically significantly*better back pain relief at ALL time points (1 wk 24 mo) ~30% or greater difference throughout the 24 months 1 0 (1wk) (1mo) 0 6 12 18 24 Follow-up (Months) 10-point back pain score (0=no pain, 10=max) SF-36 Bodily Pain Score (1 24) Reduced Bodily Pain Significantly reduced SF-36 Bodily Pain at all time points (9.75 points better than NSM over 24 mo; p<0.0001) 13 PMD006367-1.0 FREE Study Outcomes
Pain Medication & Patient Satisfaction BKP Patients Used Significantly Fewer Pain Meds Percent of patients requiring meds for fracture pain BKP NSM Any analgesics Baseline 94% 92% Narcotics (codeine or stronger) 12 months 52% 68% Baseline 73% 67% 6 months 30% 43% p = 0.01 p = 0.04 BKP Patients More Satisfied* Patients were more satisfied with BKP over 24 months (treatment effect 3.09 points, 95% CI 2.26-3.92, p<0.0001) Difference was significant at ALL time points including 24 months (24mo = 2.31 points difference, 95% CI 1.19-3.43, p<0.0001) * Likert Patient Satisfaction (Scale 1 20) 14 PMD006367-1.0 FREE Study Outcomes
Subsequent Fracture Outcomes No Difference BKP NSM P-value Patients with New Radiographic VCFs, n (%)* 0-3 months All subsequent 27/123 (22%) 27/100 (27%) 0.43 0-12 months All subsequent 45/118 (38%) 38/99 (38%) 1.00 All subsequent 56/118 (48%) 45/102 (44%) 0.68 0-24 months Adjacent 28/118 (24%) 17/102 (17%) 0.24 Worsening Index 5/118 (4%) 11/102 (11%) 0.07 Patients with New Clinical VCFs, n (%) VCFs 31/149 (21%) 27/151 (18%) 0.52 0-24 months Considered possibly device-related 11/149 (7%) N/A - Non-VCFs 20/149 (13%) 15/151 (10%) 0.35 Index = acute fractures identified at baseline to be treated according to randomization assignment (BKP or NSM). Worsening Index = any patient with an index fracture that worsened by at least one Genant grade. All Subsequent = patient with any new fracture including a worsening index or new fracture located adjacent to or remote from an index fracture. Adjacent = any patient with a new fracture located adjacent to an index fracture. * Radiographic fractures identified by core lab. Clinical fractures identified by investigators as adverse events MedDRA coded to musculoskeletal disorders. Considered to be possibly or probably related by the local investigator. Non-vertebral fractures include all other fractures (e.g., extremity, rib, hip, cranial) but exclude fractures to digits. 15 PMD006367-1.0 FREE Study Outcomes
Safety Endpoints through 24 months Similar safety profile between BKP and NSM BKP serious adverse events considered related to procedure/device 1 patient with a procedure-related post-operative urinary tract infection with subsequent spondylitis at the treated level possibly related to the cement 1 patient with a device-related subcutaneous hematoma 1 patient with worsening index fracture and anterior cement migration (possibly cement-related) No device- or procedure-related myocardial infarctions, pulmonary embolisms, neurological injuries, or deaths BKP did not result in a significant increase in number of patients with subsequent vertebral fractures or subsequent adjacent fractures 16 PMD006367-1.0 FREE Study Outcomes
Kyphon Balloon Kyphoplasty Important Safety Information The complication rate with Kyphon Balloon Kyphoplasty has been demonstrated to be low. There are risks associated with the procedure (e.g., cement extravasation), including serious complications, and though rare, some of which may be fatal. For complete information regarding indications for use, contraindications, warnings, precautions, adverse events, and methods of use, please reference the devices Instructions for Use included with the product. 17 PMD006367-1.0 FREE Study Outcomes
FREE Study Summary Level I Clinical Evidence in support of BKP Largest multicenter randomized clinical trial with 24-month follow-up supporting BKP as a beneficial treatment for acute VCFs BKP was shown to be more effective than NSM Faster and sustained pain relief Quicker return of mobility Better quality of life Greater patient satisfaction BKP is a safe procedure Overall frequency of patients with AEs and serious AEs was similar between BKP and NSM through 24 months No statistical difference in the number of patients with new radiographic or clinical fractures Only 2% of BKP patients had serious device/procedure-related AEs 18 PMD006367-1.0 FREE Study Outcomes
www.compressionfracturestudy.com www.medtronic.com Medtronic Kyphon Products Division 1221 Crossman Avenue Sunnyvale, CA 94089 Telephone: 408.548.6500 Customer Service: 866.959.7466 2011 Medtronic Spine LLC. All Rights Reserved. 19 PMD006367-1.0 FREE Study Outcomes