Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04902352 |
| Other study ID # |
RRK6941 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
April 6, 2021 |
| Est. completion date |
October 6, 2024 |
Study information
| Verified date |
November 2023 |
| Source |
University Hospital Birmingham NHS Foundation Trust |
| Contact |
Nikolaos A Chatzizacharias, FRCS |
| Phone |
07787731126 |
| Email |
Nikolaos.Chatzizacharias[@]uhb.nhs.uk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
There is a high rate of R1 resection following patients undergoing pancreaticoduodenectomy
for pancreatic cancer. The most commonly positive margin is the SMA. Peri-adventitial
dissection has been proposed as an effective method of achieving R0 margins. There is lack of
standardisation of the proposed technique and no grade 1 evidence to support routine use of
this technique.
The goal of this randomised controlled trial is to investigate the role of routine
peri-adventitial dissection on the SMA margin status.
Description:
Pancreatic cancer is the 4th cause of cancer death in Europe. With the existing treatments
the overall 5-year survival remains 8%. For patients with non-metastatic disease, many are
conventionally judged unresectable with just 10-20% eligible for upfront surgery and a 5-year
survival of 10-30%. Microscopically positive margins (R1) have been associated with poorer
survival of patients undergoing pancreaticoduodenectomy. The incidence of R1 varies between
16-79% in the published literature and the median survival for patients undergoing R0
resections is between 19-21 months versus 9-13 months for patients undergoing R1. Therefore,
to investigate strategies to decrease the rate of R1 resection is crucial to significantly
improve the patient survival1.
The SMA margin is positive in 47-77% of these resections, even when the margin is "clear" on
the pre-operative staging CT2,4. Many different techniques are in practice and have been
described for this part of the pancreaticoduodenectomy procedure, including the use of
diathermy and ties, energy devices such as Ligasure, and staplers. The main denominator is
staying close to the SMA and removing the so called "mesopancreas"3.Peri-adventitial arterial
dissection is a technique that has been a commune practise in several pancreatic centres and
has been proposed as an effective surgical technique to achieve R0 margins. On the other
hand, SMA dissection may theoretically increase the risk of acute haemorrhage, vascular
injury, and thrombosis, development of pseudo-aneurysms or persistent chyle leak due to the
extensive lymphoneural dissection. Furthermore, the published evidence reveal variability in
the definition of a "positive margin", as well as the lack of accurate description of the
surgical technique in the majority of the studies, with only about 25% of the studies
reporting the use of the technique4. Moreover, none of the published studies have documented
standardisation in the use of the technique with regards to the extent of the periadventitial
dissection on the SMA, longitudinally and circumferentially.
In the University Hospitals of Birmingham NHS Trust, pancreatic surgery is centralised in
Queen Elizabeth Hospital. Peri-adventitial dissection is selectively performed in cases where
there is a close relation of the tumour to the arteries in an effort to achieve an R0
resection. Routine practice of peri-adventitial dissection during pancreaticoduodenectomy for
resectable tumours has been performed in a subset of patients based on surgeon's preference.
The results suggest a R1 rate of 20%, with SMA margin positivity 5%, compared to a rate of
44% margin positivity within the unit, with 54% SMA R1 rate. Furthermore, complication rates
are comparable to the average described by the unit's results and published literature (20.8%
of grade B and above complications as per the Clavien-Dindo classification). More
specifically, there have been no incidences of vascular related injury or complication
related to the technique; or persistent chyle leak (one episode of chyle leak grade A
recorded that was managed conservatively).
The goal of this prospective study is to investigate the role of routine peri-adventitial
dissection on the SMA margin status. Primary outcome is SMA margin status. Secondary outcomes
are: length of stay, complications, overall survival, disease free survival and adjuvant
treatment uptake.
This will be a two arm, randomised 1:1 (periadventitial dissection : no periadventitial
dissection) study. A pilot phase will determine feasibility to proceed with the rest of the
trial and to determine:
1. Feasibility of patient recruiting and randomisation
2. Feasibility and reproducibility of the technique
3. Feasibility of use of intraoperative photography
4. Intraoperative and postoperative complication rate and severity (Clavien-Dindo
classification)
5. Positive SMA margin status rate
Feasibility criteria to be met in order to proceed with the rest of the trial:
6. Recruitment of at least 20 patients in 6 months (both arms)
7. Periadventitial dissection technique to be performed in at least 80% of the randomised
patients to that arm as documented by intraoperative photography
8. Increase in the complication rate no more than 10%
For the full trial a sample size of 51 patients per arm has been based on a margin positivity
of 44%, based on the unit's results, and expected 60% reduction (expected R1 18%) at power
80% (type A error 0.05).
