Preoperative endoscopic versus percutaneous biliary drainage in potentially resectable perihilar cholangiocarcinoma: DRAINAGE Trial

Cholestasis is a significant risk factor in the treatment of patients with
suspected perihilar cholangiocarcinoma (PHC) requiring major liver resection.
Preoperative biliary drainage (PBD) attenuates the effects of cholestasis
caused by the tumor, but there is controversy over the preferred technique of
PBD, either via endoscopic biliary drainage (EBD) or using percutaneous
transhepatic biliary drainage (PTBD). As PHC is a relatively uncommon disease
which complicates patient accrual, no randomised studies have yet been
conducted to identify the optimal method of preroperative biliary drainage. Due
to the high rate of drainage related complications there is a high need for
such a study.

This is a Dutch multi-centre study that aims to complete patient accrual
through national collaboration. Patients with resectable PHC will be randomized
to undergo either EBD or PTBD. The objective of the study is to identify a
difference in the rate of drainage related complications between EBD and PTBD
as preoperative biliary drainage in PHC.

The DRAINAGE Trial is a nationwide multi-centre randomized controlled trial
that will be conducted at the Academic Medical Centre (AMC) in Amsterdam, the
Erasmus Medical Centre (Erasmus MC) in Rotterdam, the University Medical Centre
Groningen (UMCG), the Maastricht University Medical Centre (MUMC) and the
University Medical Centre Utrecht (UMC Utrecht).

Patients with obstructive jaundice due to a perihilar cholangiocarcinoma who
are scheduled to undergo a curative resection will be allocated to either EBD
or PTBD by minimisation. The minimisation will be based on three factors:

- Centre of inclusion (AMC, UMCG, Erasmus MC, AZM or UMC Utrecht)
- Tumor progression into the bilateral segmental bile ducts (BC type 4 tumor,
yes/no)
- Drainage naivety (drainage procedure prior to inclusion, yes/no).

The study will be based on the intention-to-treat principle with a superiority
design for the primary outcome measure (i.e., the incidence of severe drainage
related complications). Crossover treatment will be allowed as specified below.

The study cannot be blinded to the patient or treating physician. A blinded
adjudication committee will evaluate all events relevant to the primary outcome
measure.

Final follow-up is at 90 days after explorative laparotomy.

The index drainage procedure is scheduled at 5 days after treatment allocation.
EBD consists of an endoscopic retrograde cholangiography and placement of a
plastic endoprosthesis through the stenosis. EBD procedures can be performed in
day-care. PTBD consists of ultrasonography-guided cannulation of dilated bile
ducts and placement of an internally-externally draining catheter. Patients who
undergo a PTBD procedure are admitted to the hospital for 1 or 2 days.

Participating subjects are not subject to an additional risk during
participation in this study. Preoperative biliary drainage is required for all
patients with resectable PHC, so patients would inevitably have been subjected
to either drainage modality. There are currently no guidelines for the choice
of EBD or PTBD in the preoperative setting, and it is current practice to use
both EBD and PTBD in a mixed fashion to accomplish sufficient drainage. In an
attempt to structure the use of EBD and PTBD, this trial aims to identify
differences between both treatment modalities.
Participation is associated with a small additional burden. This burden
includes a baseline patient history assessment, a single ultrasound 7 days
after the initial drainage procedure to assess residual dilatation of the bile
ducts, and completing quality-of-life questionnaires.

Biliary drainage has an intrinsic risk of inducing seeding metastasis after
resection of the tumor. It is currently unknown which drainage technique has
the highest risk of inducing seeding metastases. As participating patients
would have been subjected to biliary drainage anyway, participation in this
study does not carry an increased risk of inducing seeding metastases.