A Randomised Controlled Trial to Investigate the Effectiveness of ThOracic Epidural and Paravertebral Blockade In Reducing Chronic Post- Thoracotomy Pain: 2

At the present time, both thoracic epidural block (TEB) and paravertebral blockade (PVB) are routinely used in the UK to provide pain relief for patients undergoing elective open thoracotomy. TEB has long been regarded as the 'gold standard' technique of pain relief for thoracotomy but this has recently been challenged from an overview of the literature on trends and new evidence in the management of acute and chronic post-thoracotomy pain.

In TOPIC 2 the interventional arm will be peri-operative (at or around the time of surgery) pain relief using PVB and the comparator arm will be peri-operative pain relief using TEB. The only pre-operative change to the patient pathway in TOPIC 2 is that the patient will be approached during pre-operative assessment at least 24 hours prior to surgery.

Post-operatively patients will receive analgesia in line with current practice. The trial's hypothesis is that in adult patients undergoing elective open thoracotomy, the use of paravertebral blockade for pain relief at or around the time of surgery reduces both the number of people reporting chronic pain and the persistence of chronic pain at six months by at least 10%, compared with the use of thoracic epidural block. To detect this difference a total of 1026 patients will be recruited from approximately 20 UK hospitals.

Interim analyses of safety and efficacy for presentation to the independent DMC will take place during the study. The committee will meet prior to study commencement to agree the manner and timing of such analyses but this is likely to include the analysis of the primary and major secondary outcomes and full assessment of safety (SAEs) at least at annual intervals. Criteria for stopping or modifying the study based on this information will be ratified by the DMC, but there is also an embedded pilot phase which sets out criteria for assessing whether sufficient progress is made during the first 12 months of recruitment. Failure to open enough sites to recruitment or recruit enough patients from those sites, may be sufficient reason to terminate the trial, or at least re-design some of it to ease these problems.

A randomised controlled trial design has been chosen since this is the acknowledged "gold standard" for evidence based medicine and, because only the patients themselves can say how much pain they are in, patient reported outcomes are appropriate in answering the trial question. Because of the nature of the procedure it is not possible to conceal the surgical team performing the procedure from the allocation but they will not know in advance which of the allocated treatments will be received. There is no reason to believe that patients will have any preconceptions regarding the levels of chronic pain they will experience so the chance of bias is low in this regard.