Percutaneous Vertebroplasty vs. Sham for Osteoporotic Vertebral Compression Fractures Focusing on Pain and Economy.

Study Overview
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Brief Summary
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The purpose of this randomized double-blind clinical trial is to determine the efficacy of percutaneous vertebroplasty (PVP) in relieving severe pain in patients with MRI-verified acute or sub-acute osteoporotic vertebral compression fractures (OVCFs) compared to sham as well as examine the socio-economic implications associated with performing vertebroplasty. The primary outcome is improvement of pain intensity as measured on a Visual Analog Scale (VAS, 0 to100) 12 weeks after treatment. Secondary outcomes include patient-reported back-related disability, patient-reported quality of life, spinal sagittal balance, complications associated with the procedure, incidence of new OVCFs and socioeconomic costs.

Detailed Description
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The study design is a prospective, double-blind, randomized, sham-controlled clinical trial where patients are stratified into either involvement of 1-2 vertebral levels or 3-4 levels and randomized to either vertebroplasty or a sham operation. The trial is designed in accordance with the SPIRIT guidelines. Patients will be examined in the outpatient clinic at the Center for Spine Surgery and Research, Lillebaelt Hospital, Middelfart, Denmark. MRI scans and X-ray images will be performed at the radiology department at the hospital. Experienced neuro-radiologists carry out image analyses. Spine surgeons who are experienced in PVP will perform the surgical procedures. Anaesthesiologists and spine surgeons are present at the facility in case of complications, following recommendations by the National Health Authority and have the capacity/capability to decompress the spinal canal in case of cement leakage. Study subjects will be recruited from patients diagnosed with painful x-ray verified vertebral compression fractures in the Region of southern Denmark. The patients will be identified and referred to the trial site by the patients' general practitioner, chiropractor, physiotherapist, or from hospital inpatient and emergency departments in the region of Southern Denmark. Subjects will initially be stratified into two groups based on the number of OVCFs into 1-2 levels or 3-4 levels. Within each of these two groups, randomization sheets in varying blocks of 8 with an equal number of PVP and sham patients in each block will be generated using software (www.randomizer.org) and will be placed in numbered, opaque, sealed envelopes. Treatment group assignment will be performed by a scrub nurse in the surgical theatre after the patient is draped but prior to skin incision. Throughout the trial, only the surgeon and the OR-nurse will have knowledge of the treatment assignment. The patient and all assessors remain blinded to the treatment group throughout the study. During hospitalization, perioperative data on operation time, theater time and complications will be collected from the operating room staff during surgery. Upon discharge, length of stay will be recorded for each patient. After discharge, all visits to the outpatient clinic, either to the surgeon, nurse or physiotherapist as well as phone calls with questions regarding their procedure to the surgical nurse and time spent will be recorded. Patients will be seen in the clinic for evaluation at 4, 12, and 52 weeks after treatment. MRI and full-standing anteroposterior and lateral radiographs will be taken at the 12-week follow-up time point. This will allow for identification of any healing at the index level as well as any new-onset OVCFs. Treatment effectiveness analyses of the randomized trial data will performed on an intent-to-treat basis. Enrolled patients and outcome assessors will remain blinded for the duration of the trial. The 12-week follow-up will be the primary endpoint.

Official Title
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Percutaneous Vertebroplasty vs. Sham for Osteoporotic Vertebral Compression Fractures Focusing on Pain and Economy: A Single-center, Double-blind Randomized Controlled Clinical Trial

Conditions
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Osteoporotic Fractures, Vertebral Fracture

Intervention / Treatment
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* Procedure: Vertebroplasty
* Procedure: Sham Vertebroplasty


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged 50+ and diagnosed with symptomatic osteoporotic spinal compression fractures between T6 and L5 (incl). Focal tenderness on the level of the vertebral fracture. Fractures verified with oedema of the relevant vertebra on the MRI STIR sequence Osteoporotic Fractures type 1-4. Fracture involves no more than 4 vertebral body levels. PVP can be done in one session. Back pain score measured on a Visual Analog Scale (VAS, 0 to 100) ≥ 60. Able to understand and read Danish. Written informed consent. Relevant pain started ≤ 3 months prior to enrollment. Exclusion Criteria: - Contra-indications for spine surgery. Platelets < 30 mia/l. Osteoporotic Fractures type 5 and Pincer-type. Complete collapse of the vertebral body precluding insertion of needle. Presence of neurologic deficit. Contraindications for MRI scanning. Psychological or psychiatric disorder that is expected to interfere with compliance. Active malignancy. Mini Mental State Examination (MMSE) test score below 24. History of chronic back pain requiring ongoing opiate use. Systemic or local infection of the spine.

Ages Eligible for Study
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Minimum Age: 50 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vertebroplasty<br>Polymethyl-methacrylate (PMMA) cement is prepared and injected slowly into the vertebral body under constant bi-plane fluoroscopy | Procedure: Vertebroplasty<br>* PVP<br>|
| Sham Comparator: Sham vertebroplasty<br>A short needle is passed through the skin, but not as far as the periosteum. PMMA is mixed to mimic the PVP procedure but not injected into the vertebral body. | Procedure: Sham Vertebroplasty<br>* Sham PVP<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity using the 100-point VAS | Self-reported average pain intensity over the previous 24 hours, using the 100-point VAS will be recorded at time of randomization and after 1, 2, 3, 4 and 5 days, and after 2, 4, 8 and 12 weeks, and finally at 12 months and 24 months post-randomization | VAS will be recorded at time of randomization and after 1, 2, 3, 4 and 5 days, and after 2, 4, 8 and 12 weeks, and finally at 12 months and 24 months post-randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient-reported disability. | The patients rate their disability at the time of enrolment and at 4 and 12 weeks, 12 and 24 months post-randomization using the Oswestry Disability Index (ODI) questionnaire | Recorded at enrolment and at 4 and 12 weeks, 12 and 24 months post-randomization | 
| Health-related quality of life. | HRQL on the EuroQol 5-dimension 5-level (EQ-5D-5L) | Recorded at enrolment and at 4 and 12 weeks, 12 and 24 months post-randomization | 
| Global Perceived Effect scale | Global perceived effect of the treatment will be assessed using single question with seven-point descriptive scaling with the answers | Recorded at 4 and 12 weeks, 12 and 24 months post-randomization | 
| Sagittal balance | Full-length 36 lateral scoliosis radiographs taken with hands placed on the clavicles will be obtained to measure Pelvic Incidence, Pelvic Tilt, Sacral Slope, C7-Plumb Line and Lumbar Lordosis/Thoracic Kyphosis both preoperatively and after 12 months | Recorded at enrolment and 12 months post-randomization | 
| Societal costs of treatment | The intervention costs will be obtained using data from hospital registries about outpatient contacts, inpatient admissions and length of stay, staff time for surgical procedure, recovery and rehabilitation. | Recorded 1 day at discharge and 12 months post-randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vertebroplasty, Pain