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.
