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.
TOPIC 2 has been designed as a pragmatic trial which collates data during the hospital
admission for thoracotomy then, by telephone interview and postal questionnaire at 3, 6 and
12 months. This schedule of events as well as both the type and amount of data collected has
been created with substantial input from 2 patient/public representatives.
Since the track record of recruitment to trials involving surgery is not as good as in other
areas of medicine, the trial has embedded a qualitative component which will specifically
look at the consent process and the reasons for patients either entering or not entering the
trial. Patients will therefore initially be asked to consent to the conversation introducing
the trial being recorded, and to participate in the main trial. They can choose to
participate in just the interview process (conducted in the clinic), just the main trial,
neither, or both.
The trial documentation has been prepared in advance of submission to ethics and recruitment
is estimated to start in the final quarter of 2018, for 30 months. The first 12 months of
recruitment will form an internal pilot phase during which the feasibility of the overall
trial will be assessed. Although the primary outcome requires only 6 months followup,
patients will be followed up for year to provide a further estimate of how long any
differences in pain levels lasts. It will take approximately a further 6 months to analyse
the data prior to publication.
