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We are concerned by commentary1 about the VAPOUR trial2 written by authors of two previous masked vertebroplasty trials.3 4 Having participated in the larger of these trials, INVEST,3 we adopted similar trial methodology in VAPOUR but restricted patient inclusion criteria to fractures <6 weeks duration causing severe pain (table 1).
The commentary speculates that trial procedures were inadequately masked because patients could not smell polymethyl methacrylate (PMMA). We replicated the placebo used in INVEST with the exception that the selected PMMA kit emitted no odour, and lidocaine was injected into the subcutaneous rather than periosteal space, precluding therapeutic effect. Intravenous sedation, and the verbal and tactile cues suggesting vertebroplasty was being performed, were identical to INVEST.
More patients in the vertebroplasty group than placebo group correctly guessed their assigned intervention and overwhelmingly nominated pain reduction as the principle reason for their guess, presuming this indicated vertebroplasty had been performed. Consistent with this reason, the between-group difference of patients correctly guessing their assigned intervention was the same as the between-group difference experiencing substantial pain reduction.
Unlike the other studies, the primary outcome for VAPOUR was the achievement of a benefit threshold of which patients were not aware (reinforcing the credibility of the result) so that even if patients correctly guessed their treatment, they were nevertheless unaware to the outcome benefit threshold. This was not the case in the other studies, and the extent to which recall bias may have influenced their results was not measured.
The ‘highly selected’ study population reflects appropriate selection criteria.5 Enrolment differences between centres is similar to the previous, smaller trial4 except that, unlike that trial, VAPOUR met the required enrolment target specified in the study design.
The assertion that only fractures ≤3 weeks duration in the thoracolumbar spine benefited from vertebroplasty is incorrect. Lack of efficacy in fractures >3 weeks and non-thoracolumbar fractures was not demonstrated in subgroup analysis.
The VAPOUR trial shows that patients with severe, uncontrolled pain due to osteoporotic, spinal fractures <6 weeks duration derive sustained benefit from early intervention with vertebroplasty. Contrary to the ‘known favourable natural history,’ the placebo group had poor outcomes persisting to 6 months and experienced worse complications than the vertebroplasty group.
Patients hospitalised with acute spinal fractures have severe pain and very recent fractures and are good candidates for vertebroplasty. They comprised 57% of patients in the VAPOUR trial but were either specifically excluded3 or not reported4 in the outpatient trials conducted by the authors of the commentary.
Competing interests None declared.
Provenance and peer review Not commissioned; internally peer reviewed.
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