KAVIAR Study - Kyphoplasty And Vertebroplasty In the Augmentation and Restoration of Vertebral Body Compression Fractures

Study Overview
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Brief Summary
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Patients with osteoporotic vertebral body compression fractures will be randomly assigned to treatment with balloon kyphoplasty or vertebroplasty. Over 2 years of follow-up, back pain, back function, quality of life, adverse events, subsequent fractures and cumulative healthcare costs will be compared.

Detailed Description
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Medtronic Spine LLC is sponsoring the KAVIAR study, a randomized clinical trial comparing balloon kyphoplasty to vertebroplasty for the treatment of osteoporotic vertebral body compression fractures (VCFs). Up to 1,234 subjects at up to 75 study centers with one to three VCFs and VB morphologies suitable for both balloon kyphoplasty and vertebroplasty will be randomly assigned to receive one or the other procedure. Study visits will occur at baseline, 30 days postoperatively, and at 3, 12 and 24 months postoperatively. At all visits, adverse events, back pain, back function and quality of life will be assessed. In addition, a 7-day phone call will be conducted, which will include assessment of back pain, narcotic use and adverse events. At baseline, pre-discharge, 3-, 12- and 24-month visits, lateral spine x-rays will be taken. The primary endpoint will be the proportion of patients with one or more subsequent fractures at 12 and 24 months, detected radiographically as determined by a core radiology laboratory. Secondary clinical endpoints include changes from baseline in back pain, back function and quality of life, and adverse events. Secondary radiographic comparisons include the restoration and maintenance of VB height and angulation, and sagittal vertical axis, a measure of global sagittal balance. A postoperative CT scan will be evaluated to detect cement extravasation and to examine the relationship between cement distribution and clinical outcomes. Another important feature of the study is a detailed healthcare utilization data assessment. Combined with a costing methodology based on Medicare cost data and other sources, cumulative two-year healthcare costs related to VCF will be estimated. Combined with quality of life measurements, the cost analysis will allow a calculation of the relative cost-effectiveness of balloon kyphoplasty and vertebroplasty. Sample size is based on the primary endpoint, the proportion with subsequent fractures at 12 and 24 months.

Official Title
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A Multicenter, Randomized, Prospective Clinical Trial to Compare the Short- and Long-term Safety and Effectiveness of Balloon Kyphoplasty to Vertebroplasty in the Treatment of Painful, Acute Osteoporosis-related Vertebral Body Compression Fractures (VCFs).

Conditions
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Vertebral Body Compression Fractures

Intervention / Treatment
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* Procedure: Vertebroplasty
* Procedure: Kyphoplasty


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria All subjects must meet all of the following criteria to be enrolled into the study: Age > 21 1 to 3 target VCFs meeting the following criteria: Fracture due to diagnosed or presumed underlying primary or secondary osteoporosis All target VCFs are between T5 and L5 All target VCFs to be treated show either: i. Height change: An acute (< 6 month) change in VB height or morphology from a previous x-ray, CT or MRI, with height loss at the anterior, middle or posterior portion of the VB consistent with a worsening of 1 or more grades by the Genant criteria (17), OR ii. Positive MRI or bone scan: VB shows hyperintense signal on STIR sequence MRI or target VB is positive on radionuclide bone scan All VCFs to be treated have fracture age (time from pain onset to evaluation by the Investigator) of 6 months or less Back pain correlating with the location of at least one VCF Treatment of all target VCFs is technically feasible by and clinically appropriate for BOTH vertebroplasty and balloon kyphoplasty. (Team approach only: Both the vertebroplasty and balloon kyphoplasty physician have reviewed radiographic studies and agree to this prior to enrolling the subject in the study.) Pre-treatment back pain by numerical rating scale (NRS) score > 4 (0-10 scale) Pre-treatment Oswestry Disability Index >20 (0 - 100 scale) Subject states availability for all study visits Subject is able to understand the risks and benefits of participating in the study and is willing to provide written informed consent Subject has mental capacity to comply with the protocol requirements for 2-year duration of study Exclusion Criteria Subjects who meet any of the following conditions may not be enrolled into the study: VB morphology or configuration is such that either balloon kyphoplasty OR vertebroplasty is not technically feasible for the targeted VCFs Fracture due to high-energy trauma Suspected OR proven cancer inside index vertebral body. Note that patients with chemotherapy-related osteoporosis may be included. Disabling back pain due to causes other than acute fracture (e.g., sacroiliac fracture, symptomatic degenerative disc disease, lumbar spinal stenosis) Any painful VCF with fracture age > 6 months Any objective evidence of neurologic compromise at baseline Previous balloon kyphoplasty or vertebroplasty for any VCF Spine stabilization beyond balloon kyphoplasty or vertebroplasty required for targeted VCFs Significant clinical comorbidity that may potentially interfere with long-term data collection or follow-up (e.g., dementia, severe comorbid illness) Pre-existing conditions contrary to either balloon kyphoplasty or vertebroplasty, such as: Irreversible coagulopathy or bleeding disorder. Note regarding reversible coagulopathies: Subjects on coumadin or other anticoagulants may participate. Investigators should follow routine practices for perioperative discontinuation and re-initiation of anticoagulants. Allergy to any device materials (e.g., bone cement) for balloon kyphoplasty or vertebroplasty. Note that in subjects with allergy to iodine-based contrast, other non-iodine contrast solutions may be used. Any evidence of VB or systemic infection Pregnant or child-bearing potential

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Kyphoplasty<br> | Procedure: Kyphoplasty<br>* Balloon Kyphoplasty involves two inflatable bone tamps placed into the vertebral body in the spine. After the tamps are removed, the void is filled with viscous bone cement.<br>|
| Active Comparator: Vertebroplasty<br> | Procedure: Vertebroplasty<br>* Vertebroplasty involves placement of a needle into the vertebral body. Cement is injected into the vertebral body.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent of Subjects With One or More Subsequent Radiographic Fractures at 12 Months |  | 12 months | 
| Percent of Subjects With One or More Subsequent Radiographic Fractures 24 Months |  | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Back Pain | Back pain was assessed on a 10-point Numerical Rating Scale (NRS) from 0 (no pain) to 10 (worst possible pain). | 7 days, 30 days, 3 months, 12 months, 24 months post-operation | 
| Back Function-Oswestry Disability Index | The Oswestry Disability Index (ODI) Questionnaire was used to assess patient back function. The ODI score ranges from 0-100. The best score is 0 (no disability) and worst is 100 (maximum disability). | 30 days, 3 months, 12 months, 24 months post-operation | 
| Quality of Life by SF-36 | The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) was used to assess general health status. The SF-36 results are summarized into two components, a physical component summary (PCS) and a mental component summary (MCS). The score for PCS and MCS is between 0 and 100, with higher scores denoting better quality of life. | 30 days, 3 months, 12 months, 24 months post-operation | 
| Quality of Life -- EQ5D Index | EQ-5D index scores range from 0 to 1.0 on a scale where 0 = death and 1.0 = perfect health. | 30 days, 3 months, 12 months, 24 months post-operation | 
| Rate of Serious Adverse Events at 30 Days | Rate of serious adverse events is presented as the percentage of the participants who reported serious adverse events within 30 days after initial treatment. For this study, serious adverse events (SAEs) included death, serious deterioration in health, life threatening injury/illness, hospitalization or prolonged hospitalization, or resulted in medical or surgical intervention. | 30 days post-operation | 
| Rate of Procedure/Device Related or Possibly Related Serious Adverse Events at 30 Days | Rate of Procedure/Device related or possibly related serious adverse events is presented as the percentage of the participants who reported Procedure/Device related or possibly related serious adverse events within 30 days after initial treatment. | 30 days post-operation | 
| Change in Anterior Vertebral Body Height |  | Pre-op, Pre-discharge, 3 months, 12 months, 24 months post-operation | 
| Change in Middle Vertebral Body Height |  | Pre-op, Pre-discharge, 3 months, 12 months, 24 months post-operation | 
| Change in Posterior Vertebral Body Height |  | Pre-op, Pre-discharge, 3 months, 12 months, 24 months post-operation | 
| Change in Vertebral Body Kyphosis Angle | The vertebral kyphosis angle was defined as the angle formed by lines drawn parallel to the superior and inferior endplates of the treated fractured vertebral body. | Pre-op, Pre-discharge, 3 months, 12 months, 24 months post-operation | 
| Change in Vertebral Body Local Cobb Angle (LCA) | The vertebral body local Cobb angle is a measurement of the 3-level functional unit consisting of the treated fractured vertebral body and the nearest adjacent vertebrae and is defined as the angle formed by lines drawn parallel to the superior endplate of the cranial adjacent vertebral body and the inferior endplate of the adjacent caudal vertebral body. | Pre-op, Pre-discharge, 3 months, 12 months, 24 months post-operation | 
| Change in Global Sagittal Balance. | Change in global sagittal balance as measured by sagittal vertical axis. | Pre-op, Pre-discharge, 3 months, 12 months, 24 months post-operation | 
| VCF-related Health Care Utilization | Health care utilization assessments conducted by monthly phone call to participating patients. | Monthly for 24 months post-op | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kyphoplasty, Vertebroplasty, Balloon Kyphoplasty, Inflatable Bone Tamp, Spine, Back Pain, Vertebral Compression Fracture, Vertebral Body Compression Fracture