Trial Information

A Double Blind, Randomized Controlled Prospective Trial of Endo-biliary Radio-frequency Ablation for Maintenance of Metal Stent Patency in Patients With Malignant Obstructive Jaundice

We assume that application of endobiliary RFA to the malignant stricture which results in
considerable charring of the tumor would result in prolongation of Self-expandable metal
Stent (SEMS) patency by decreasing tumor in-growth and overgrowth. It is further speculated
that prolonged stent patency will improve the quality of life of these patients, prevent
cholangitis and optimize chemotherapy. A further outcome may be an improvement in the
survival.

The research questions which we intend to answer through this trial would be:

1. Does application of prior endo-biliary radiofrequency affect patency of SEMS?

2. What are the complications associated with the use of endo-biliary RFA?

3. Does endo-biliary RFA with immediate placement of SEMS improve patient survival?

4. Is there any improvement in the quality of life of the patient with the combined use of
endo-biliary RFA and SEMS?

Study protocol:

The study design is a double blind, sham operated, randomized controlled trial.

Inclusion criteria:

1. Patients: Clinical data and investigations suggestive of unresectable malignant bile
duct obstruction. All patients will be discussed at the hepato-biliary
multidisciplinary meeting which should come to a unanimous decision on tumor
unresectability.

2. Age more than 18 years

3. Histologically/ Cytologically confirmed malignancy

4. Informed consent: The patient should voluntarily agree to participation and
randomization. Oral and written information about the nature of the trial will be given
to all patients considered for inclusion.

Exclusion Criteria:

1. Informed consent not obtained or withdrawn

2. Extremely poor general condition not amenable for conscious sedation used for
Endoscopic retrograde Cholangiography (ERC)

3. Candidate suitable for surgical resection

4. Klatskin type 4 tumor

5. Previous biliary intervention such as plastic stent insertion for more than 1 month

6. Any other contra-indication to ERC

Randomization:

After obtaining an informed consent and satisfying the inclusion criteria, the patients will
be randomized to one of the following two arms using computer generated randomization
blocks. The operator and the patient will be blinded to use of RFA

1. Experimental arm: Insertion and activation of the endo-biliary RF catheter at the site
of the stricture before insertion of a SEMS

2. Control arm: Insertion and sham activation of the endo-biliary RF catheter at the site
of the stricture before insertion of a SEMS.

All patients will get the same SEMS with variable lengths (depending on the stricture size)
to maintain uniformity. Endoscopic sphincterotomy will be performed in all patients prior to
endo-biliary RF application and SEMS insertion. Opacification of the cystic duct and whether
the endo-biliary RFA catheter was placed at the cystic duct opening will be recorded.

Data Collection:

Baseline data will be collected by an advanced endoscopy fellow and will include age,
gender, WHO performance score, presence of gall bladder or gall stones, primary tumor type
and stage, baseline liver function test, adjuvant chemo/radiotherapy

After discharge from the hospital, the patients will be followed up in the clinic at 1 week,
1 month, 3 months, 6 months, 9 months and 12 months. At each visit, a detailed clinical
history, examination, adverse events, adjuvant therapy and liver function tests will be
carried out. Patients will be assessed according to the World Health Organization
performance classification.

WHO score

- 0 - Asymptomatic (Fully active, able to carry on all predisease activities without
restriction)

- 1 - Symptomatic but completely ambulatory (Restricted in physically strenuous activity
but ambulatory and able to carry out work of a light or sedentary nature. For example,
light housework, office work)

- 2 - Symptomatic, <50% in bed during the day (Ambulatory and capable of all self care
but unable to carry out any work activities. Up and about more than 50% of waking
hours)

- 3 - Symptomatic, >50% in bed, but not bedbound (Capable of only limited self-care,
confined to bed or chair 50% or more of waking hours)

- 4 - Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to
bed or chair)

- 5 - Death All patients will be referred for an oncological opinion for palliative
chemotherapy. The patients and their care-givers will be told about symptoms of
cholangitis and stent obstruction and will be asked to contact the hospital immediately
in such cases. In the event of a confirmed SEMS occlusion, either a new SEMS or a
plastic stent will be placed depending on the patient's prognosis.

End points:

1. Stent occlusion:

1. Cholangitis

2. or serum bilirubin > 3mg/dL with a previously normal bilirubin or above the
baseline.

3. Any clinical jaundice should be confirmed as being caused by stent occlusion by
imaging or ERC

2. Death

3. Uneventful follow-up for 12 months

Evaluation:

The primary aim will be to compare the two groups for duration of stent patency.

The secondary aims will be:

1. To study any complications attributable to endo-biliary RFA

2. To study if there is any improvement in patient survival

3. To study if there is any improvement in patient's quality of life

Statistics:

We assume that the metal stent patency will improve from 50% to 80% at 6-8 months. With a
80% power and alpha error of 5%, we will need 43 patients in each arm. The Fisher exact test
will be used to evaluate any differences in the patient distribution. The Student unpaired t
test will be used to compare the laboratory tests, age and sex. Cumulative stent patency and
patient survival will be estimated using the Kaplan-Meier method.