Ultrasound-guided Percutaneous Biliary Drainage Versus Endoscopic Ultrasound-guided Biliary Drainage

Study Overview
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Brief Summary
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Prospective multi-site study of ultrasound-guided percutaneous biliary drainage and endoscopic ultrasound-guided biliary drainage with implantation of a self-expanding metal stent in patients with malignant, distal bile duct obstruction (PUMa-study)

Detailed Description
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In a recent systematic review and meta-analysis about the efficacy and safety of endoscopic ultrasound-guided biliary drainage (EUBD) in comparison with percutaneous transhepatic biliary drainage (PTBD), there was no difference in technical success between the two procedures, but PTBD was associated with a lower level of clinical success, a higher level of post-procedural adverse events and a higher rate of re-interventions. The authors concluded that EUBD should be favored for biliary drainage when endoscopic retrograde cholangiopancreaticography (ERCP) failed or wasn´t possible to perform due to anatomical reasons. The hypothesis of this prospective multicenter study is that PTBD wasn´t performed in an appropriate way to compare it adequately with EUBD. The following improvements should be done. First, color Doppler ultrasound-guidance for cannulating the bile duct should be used in PTBD. The transgression of blood vessels with the risk of severe intrahepatic bleedings or hemobilia can be avoided, which are common adverse events in PTBDs when it is performed by fluoroscopic guidance. Second, the access to the bile duct from the left side of the liver should be favored. The access from the right liver side causes more adverse events such as biliary effusion or pneumothorax, as well as more patient discomfort and pain. Third, implantation of the self-expanding metal stent should be performed in the first session as a one-step procedure. This has the advantage that no further re-intervention is necessary after insertion of an external or an external/internal drainage, an outcome which can cause further adverse events such as bile duct leak along the catheter, biliary ascites or catheter dislocation. Fourth, stent release should be performed under endoscopic luminal guidance. In this way, the positioning and the correct expansion of the distal tip of the metal stent can be observed directly in comparison with the stent release which is only controlled by fluoroscopic guidance. On the other hand, EUBD should be performed in its best manner (special metal stents included) with the three techniques that are usually necessary to perform a successful EUBD: EUS-guided antegrade transpapillary drainage, EUS-guided transhepatic drainage and EUS-guided choledochal drainage. The study focuses on patients with malignant distal (infra-hilar) bile duct obstruction. It is presumed that the technical and clinical success rate is equal (non-inferiority) but the adverse event rate, the number of re-interventions and the number of days of hospitalization may differ between the two interventions. An adequate number of cases (106 patients in each intervention, drop outs included) should be recruited to calculate relevant statistical differences. Furthermore, patients will be followed over six months after the intervention to calculate an estimated survival analysis (with and without palliative chemotherapy).

Official Title
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Prospective Multi-site Study of Ultrasound-guided Percutaneous Biliary Drainage and Endoscopic Ultrasound-guided Biliary Drainage With Implantation of a Self-expanding Metal Stent in Patients With Malignant, Distal Bile Duct Obstruction

Conditions
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Bile Duct Obstruction, Extrahepatic

Intervention / Treatment
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* Procedure: US-guided percutaneous biliary drainage
* Procedure: EUS-guided biliary drainage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inoperable, malignant disease with extrahepatic bile duct obstruction (infra- hilar) ERCP was not successful or wasn´t possible due to anatomical reasons (for example status post-gastrectomy) At least twofold elevated bilirubin level (> 2mg/dl) Histologically verified malignant disease Abdominal ultrasound was performed Computed tomography or magnetic resonance imaging of the abdomen was performed A written consent was given Exclusion Criteria: Relevant blood coagulation disorder (Quick < 50%, Partial thromboplastin time > 50 sec., thrombocytes < 50/nl) Extrahepatic cholangiocellular carcinoma (Klatskin tumor) Bismuth II-IV or intrahepatic cholangiocellular carcinoma Operable, malignant disease or disease which can be cured by chemotherapy (for example aggressive Non Hodgkin-lymphoma) Pregnancy or breastfeeding Participation in another trial concerning PTBD or EUBD

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: prospective, non-randomized multicenter study (each center performs the intervention which can do best)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: US-guided percutaneous biliary drainage<br>The initial percutaneous transhepatic puncture of the bile duct is performed by ultrasound guidance with a Chiba-needle (0.7 mm). After injection of a radiopaque contrast media into the bile duct system, the malignant extrahepatic bile duct stenosis can be visualized by fluoroscopic guidance (digital remote-controlled fluoroscopy device). Then a 0.018 inch guide wire is introduced and proceeded beyond the tumor stenosis into the duodenum. Next, the Chiba needle is exchanged by a 5 F catheter and the 0.018 inch guide wire is exchanged by a 0.035 inch guide wire. After dilatation of the hepatic access route with bougies up to 12 F, a self-expandable metal stent is introduced. The placement of the metal stent is controlled by endoscopic luminal guidance (gastroscope or duodenoscope). | Procedure: US-guided percutaneous biliary drainage<br>* Device: metal stent. The self-expandable metal stent is implanted percutaneously by a transhepatic access route. The metal stent is partially covered or non-covered (in cases in which the gallbladder is not removed). Length: 6-10 cm. Diameter: 8-10 mm.<br>* Other names: WallFlex™ Biliary RX Stents Boston Scientific;|
| Experimental: EUS-guided biliary drainage<br>The initial transluminal puncture of the bile duct is performed by endoscopic ultrasound guidance (longitudinal echoendoscope) with an 19 G access needle. After injection of a radiopaque contrast media into the bile duct system, the malignant extrahepatic bile duct stenosis can be visualized by fluoroscopic guidance. Then, a 0.035 inch guide wire is introduced into the bile duct. After dilatation of the transluminal access route with a balloon catheter, a self-expandable metal stent is introduced as an antegrade biliary drainage, a transhepatic biliary drainage or a choledochal biliary drainage. The placement of the metal stent is controlled by fluoroscopic and endoscopic luminal guidance. | Procedure: EUS-guided biliary drainage<br>* Device: metal stent. The transluminal (transgastric, transduodenal or transenteric) implanted self-expandable metal stent is released via echoendoscope. The metal stent is partially covered or non-covered (in cases in which the gallbladder is not removed) or mixed covered (one half covered, one half non-covered). The mixed covered stent is used for the transhepatic access. Length: 6-10 cm. Diameter: 8-10 mm.<br>* Other names: WallFlex™ Biliary RX Stents Boston Scientific;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Technical success | Successful implantation of a self-expanding metal stent to drain the obstructed bile duct, measured by the successful drainage of the radiocontrast agent by the metal stent | 1 minute after injection of a radiocontrast agent into the expanded metal stent | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical success | Decrease of bilirubin level on more than a half of the initial value | 7 days after the intervention | 
| Adverse events | All adverse events caused by the intervention | Up to 30 days after the intervention | 
| Re-interventions | Number of re-interventions (PTBD or EUBD) that are necessary in the follow up (for example due to due stent occlusion or stent migration) after successful stent implantation | 6 months after successful implantation of the metal stent | 
| Duration of the procedure | Duration of biliary drainage procedure (US-guided percutaneous biliary drainage or EUS-guided biliary drainage) in minutes | The day of the performed procedure (24 h), usually from 10 minutes up to 180 minutes | 
| Length of hospital stay | Length of hospital stay from the day of the first intervention (PTBD or EUBD) to the the day of discharge (days) | The day of the first PTBD or EUBD is counted as day 1 of hospital stay. The day of the discharge from the hospital is counted as the last day of hospital stay. An average 7 to 14 days is estimated.y. | 
| Survival time | Time from the day of intervention to the death of the patient | Follow up of six months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ultrasound-guided percutaneous transhepatic biliary drainage, endoscopic ultrasound-guided antegrade biliary drainage, endoscopic ultrasound-guided transhepatic biliary drainage, endoscopic ultrasound-guided choledochal biliary drainage, self-expandable metal stent, malignant bile duct obstruction