Article Text

Download PDFPDF

Criticisms of the VAPOUR trial in a recent commentary are unsubstantiated and incorrect
  1. William Clark1,
  2. Paul Bird2,
  3. Terry Diamond2,
  4. Peter Gonski3,
  5. Elizabeth Barnes4,
  6. Val Gebski4
  1. 1 Interventional Radiology, St George Private Hospital, Sydney, New South Wales, Australia
  2. 2 Univsersity of New South Wales, St George and Sutherland Clinical School, Kogarah, New South Wales, Australia
  3. 3 University of New South Wales - Randwick Campus, School of Public Health and Community Medicine, Randwick, New South Wales, Australia
  4. 4 University of Sydney - Camperdown and Darlington Campus, NHMRC Clinical Trials Centre, New South Wales, Sydney, Australia
  1. Correspondence to William Clark, St George Private Hospital Interventional Radiology, 1 South Street, Sydney, New South Wales, 2217, Australia; williamxrayclark{at}bigpond.com

Statistics from Altmetric.com

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).

Table 1

Comparison of inclusion criteria, baseline fracture duration and NRS pain measures, baseline hospitalisation status prior to enrolment, placebo and masking analysis, crossover and primary endpoints in the three masked vertebroplasty trials that have been published

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.

References

  1. 1.
  2. 2.
  3. 3.
  4. 4.
  5. 5.
View Abstract

Footnotes

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; internally peer reviewed.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.