A Trial of Vertebroplasty for Painful Acute Osteoporotic Vertebral Fractures
Condition: Osteoporosis; Vertebral Fracture
MeSH terms: Osteoporosis; Fractures, Bone; Spinal Fractures
Study type: Interventional
Phase: Phase 3

Summary: 
      The standard care in patients with a painful osteoporotic vertebral compression fracture
      (VCF) is conservative therapy. Percutaneous vertebroplasty (PV), is a new minimally invasive
      technique for pain treatment in which bone cement is injected in the fractured vertebra.
      Recent RCTs provide conflicting results: two sham-controlled studies show no benefit of PV
      while an unmasked but controlled RCT found significantly better pain relief after PV at
      acceptable costs.
    

Detailed description: 
      Objectives To evaluate the efficacy of bone cement injection in PV for patients with acute
      painful osteoporotic compression fractures, as compared with a simulated placebo procedure
      without injection of bone cement. We hypothesize that patients who had undergone PV would
      report less pain at 1 day, 1 week and 1, 3, 6 and 12 months (the primary outcomes) than those
      in the sham control group.

      Study design VERTOS IV is a multicenter RCT concerning the treatment of patients with a
      painful osteoporotic VCF. Patients are recruited on the Radiology departments of the
      participating hospitals and randomized to PV or a simulated procedure. Upon obtaining
      informed consent an independent central telephone operator completes the randomisation
      procedure, using a computer program. The maximum allowed unbalance (block size) is six, with
      a maximum sample size of 84 for each participating centre. A total of 180 patients will be
      enrolled, 90 in each group. This is based on the assumption of a 1.5 point difference in pain
      relief (VAS Score) and a 20% withdrawal rate (α=0.05 and β=0.20, 7 measurement points). The
      enrolment of patients will take place in four centres in The Netherlands: St. Elisabeth
      Ziekenhuis in Tilburg, Catharina Ziekenhuis in Eindhoven, Medisch Spectrum Twente in Enschede
      and Albert Schweitzer Ziekenhuis in Dordrecht. Randomization will start January 2011 with an
      expected completion of enrolment by January 2013. There is a one-year follow-up, with the
      possibility of an extended follow-up at two years.

      The overall Institutional Review Board is approval is obtained at the St. Elisabeth Hospital
      in Tilburg. In addition, each participating centre will obtain a local Institutional Review
      Board Approval. This study is registered at ClinicalTrials.gov., NCT01200277.

      Osteoporosis- and pain medication All patients receive osteoporosis medication, such as
      bisphosphonates together with supplemental calcium and vitamin D. Pain medication demanded by
      the patient is recorded. Analgesics are classified following the WHO classification: (1)
      Paracetamol (acetaminophen), (2) Tramadol, (3) Tramadol and Paracetamol, (4) Morphine. Non
      Steroid Anti Inflammatory Drugs (NSAID) are only prescribed if patients are intolerant for
      opiate-derivatives or when already used. Corrections in dose and classification of pain
      medication are made if necessary.

      Clinical follow-up An experienced nurse-practitioner requests patients to fill out a standard
      questionnaire before and at 1 day, 1 week, and 1, 3, 6 and 12 months after the procedure. The
      questionnaire consist of the VAS score and questions about use of pain medication, pain
      location, and pain type. The VAS score is a pain score ranging from 0 (no pain) to 10 (worst
      pain ever. Other medical treatment and visits to alternative medical specialists, GP's and
      physical therapists are recorded and compared between groups. Secondary outcomes are back
      pain related disability and QOL as measured with the Roland Morris Disability (RMD)
      Questionnaire and the Questionnaire of the European Foundation for Osteoporosis (Qualeffo),
      respectively. The Qualeffo is developed specifically for patients with osteoporosis. This
      questionnaire consists of 41 questions about: pain, physical function, social function,
      general health perception, and mental function. The Qualeffo score ranges from 0 (best
      quality of life) to 100 (worst quality of life). This questionnaire will be completed at five
      measurement moments (before and at 1, 3, 6, and 12 months after the procedure). The RMD
      questionnaire is a disability questionnaire that measures the functional status of patients
      with back pain. The RMD will be completed at all measurement points. All patients visit the
      internist at 1,3,6 and 12 months follow-up. All patients receive a pain diary. Patients are
      asked to fill out the VAS score and use of analgesics is recorded on a daily basis during the
      first month after randomization.

      Sample size considerations Assuming a 1.5 point difference in pain relief as measured by VAS
      score and a withdrawal rate of 20% (α=0.05 and β=0.20, 7 measurement points), a total of 180
      patients will be enrolled, 90 in each group.

      Statistical analysis The data will be analysed according to the intention-to-treat principle.
      Standard statistical techniques will be used to describe characteristics of patients in both
      groups. We will compare baseline characteristics in the two treatment groups and if
      incomparability appears, we will in secondary analysis adjust for differences. The primary
      outcome, significant pain relief will be compared with the analysis of variance for repeated
      measures. If adjustment for possible baseline incomparability is needed, analysis of
      covariance will be done. Since we expect the difference between the two groups will
      particularly become evident at 3, 6 and 12 months, the analysis will also be performed at
      these time points.
    

Intervention name(s): percutaneous vertebroplasty; sham procedure
Intervention type(s): Procedure; Procedure
Intervention description(s): Using fluoroscopic guidance, the practitioner infiltrates the skin and subcutaneous tissues overlying the pedicle of the target vertebra or vertebrae with 1% lidocaine and infiltrates the periosteum of the pedicles with 0.25% bupivacaine (marcaine. For the vertebroplasty procedure, 11-gauge or 13-gauge needles are passed into the central aspect of the target vertebra or vertebrae. Bone cement is prepared on the bench and injected under constant fluoroscopy into the vertebral body. Injection is stopped when the PMMA reaches to the posterior aspect of the vertebral body or leaks into an extraosseous space, such as the intervertebral disk or an epidural or paravertebral vein.; Using fluoroscopic guidance, the practitioner infiltrates the skin and subcutaneous tissues overlying the pedicle of the target vertebra or vertebrae with 1% lidocaine and infiltrates the periosteum of the pedicles with 0.25% bupivacaine (marcaine. During the sham intervention, verbal and physical cues, such as pressure on the patient's back, are given, and the methacrylate monomer is opened to simulate the odor associated with mixing of cement, but the needle is not placed and cement is not injected.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: osteoporosis; vertebral fracture; vertebroplasty; percutaneous