The effect of tamsulosin on the spontaneous passage of bile stones

Due to the rise in obesity the number of patients with biliary stones in the
common bile duct (CBD) rises as well. Currently it is common practice to remove
these biliary stones during an endoscopic retrograde cholangiography (ERC). In
up to 22-54% of patients with biliary stones in the CBD, the stones
spontaneously pass in to the duodenum. This patient group does not need an
invasive procedure like ERC. Urologists successfully use tamsulosin, an α1-
antagonist, to improve expulsion of ureteral stones. In vitro and in vivo
studies show relaxation of the sphincter of Oddi and the smooth muscle tissue
surrounding the CBD in cats, when an α-antagonist is administered. Human
research shows similar findings. One study has shown α-antagonists to improve
the expulsion of biliary stones in the CBD. The hypotheses in this study is:
use of Tamsulosin improves expulsion of biliary stones in the CBD.

Primary objective:
1. Determine difference in stone expulsion rate with -and without Tamsulosin

Secondary objectives:
1. Time to stone expulsion
2. Stone expulsion rate in patients with cholangitis with -and without
Tamsulosin
3. Adverse events
4. Usage of morphine

We are aiming for a single center double blind randomized controlled trial
comparing use of Tamsulosin (intervention group) and placebo (control group) in
patients with biliary stones in the CBD. The intervention group will receive
Tamsulosin 0.4mg, to be taken once a day until endoscopic retrograde
cholangiography (ERC) or objectivated stone passage during endoscopic
ultrasound (EUS). The control group receives a placebo with similar features as
Tamsulosin, to be taken once a day until ERC or objectivated stone passage
during EUS as well. All patients with biliary stones on EUS will get a
subsequent ERC, to remove remaining biliary stones. During ERC the endoscopist
will look for signs suggesting spontaneous passage of biliary stones. Such as,
the aspect of the duodenal papilla, presence of stones on cholangiogram,
passage of stones in to the duodenum during the ERC procedure, this will be
reported in all ERC reports.

This study does not delay the routine interventions of management of CBD
stones. The clinician and availability of ERC will determine the time to ERC.
For example, patients with cholangitis will be more likely to get an early ERC
compared to patients without cholangitis.

One of the following criteria must be present to state the biliary stone has
passed in to the duodenum:
- Absence of colic pain and a 50% decrease in liver test abnormalities
- Absence of biliary stone(s) during EUS/ERC

In order to reduce bias both patient and clinician will be blinded. This is
done by the pharmacy department where Tamsulosin and placebo will be stored and
from where it will be distributed. Before the start of the study a list with
inclusion number and either Tamsulosin or placebo will be made with a
randomization program. The pharmacy department will be in possession of this
list in order to be able to distribute the right medication.
The study will be a single center study taking place in the *Franciscus
Gasthuis & Vlietland* in Rotterdam.

The intervention group will receive Tamsulosin (Tamsulijn) 0.4mg once daily
until either ERC or objectivation of stone passage with endoscopic ultrasound.
The control group will receive a placebo once daily until either ERC or
objectivation of stone passage with endoscopic ultrasound.

Use of co-intervention

The use of analgesics according the WHO pain ladder is permitted. Use of
spasmolytics for example scopolaminebutyl (buscopan) is prohibited, since these
substances could influence study results.

Only participants randomized to the intervention group have the limited risk of
experiencing mild side effects of Tamsulosin. The most common side effects
(1-10%) are: dizziness, orthostatic hypotension, problems ejaculating e.g.
anejaculation or retrograde ejaculation. No other risks are expected.