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

Bile Duct Obstruction, Extrahepatic Clinical Trial

— PUMa  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03546049
• Other study ID #: 2018-PUMa-3-12-001
• Status: Recruiting
• Phase: N/A
• Start date: December 1, 2018
• Est. completion date: December 1, 2024

Study information

• Verified date: August 2023
• Source: Theresienkrankenhaus und St. Hedwig-Klinik GmbH
• Contact: Daniel Schmitz, Dr.med.
• Phone: 00496214245575
• Email: d.schmitz[@]theresienkrankenhaus.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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)

Description:

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 216
• Est. completion date: December 1, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Bile Duct Obstruction, Extrahepatic
• Cholestasis
• Cholestasis, Extrahepatic

Intervention

Procedure:
• US-guided percutaneous biliary drainage
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.
• EUS-guided biliary drainage
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.

Locations

Country	Name	City	State
Germany	Tertiary referral hospital: Theresienkrankenhaus und St. Hedwig Hospital	Mannheim

Sponsors (2)

Lead Sponsor	Collaborator
Theresienkrankenhaus und St. Hedwig-Klinik GmbH	University Hospital Heidelberg

Country where clinical trial is conducted

Germany, 

References & Publications (9)

Artifon EL, Aparicio D, Paione JB, Lo SK, Bordini A, Rabello C, Otoch JP, Gupta K. Biliary drainage in patients with unresectable, malignant obstruction where ERCP fails: endoscopic ultrasonography-guided choledochoduodenostomy versus percutaneous drainage. J Clin Gastroenterol. 2012 Oct;46(9):768-74. doi: 10.1097/MCG.0b013e31825f264c. — View Citation

Bapaye A, Dubale N, Aher A. Comparison of endosonography-guided vs. percutaneous biliary stenting when papilla is inaccessible for ERCP. United European Gastroenterol J. 2013 Aug;1(4):285-93. doi: 10.1177/2050640613490928. — View Citation

Khashab MA, Valeshabad AK, Afghani E, Singh VK, Kumbhari V, Messallam A, Saxena P, El Zein M, Lennon AM, Canto MI, Kalloo AN. A comparative evaluation of EUS-guided biliary drainage and percutaneous drainage in patients with distal malignant biliary obstruction and failed ERCP. Dig Dis Sci. 2015 Feb;60(2):557-65. doi: 10.1007/s10620-014-3300-6. Epub 2014 Aug 1. — View Citation

Lee TH, Choi JH, Park do H, Song TJ, Kim DU, Paik WH, Hwangbo Y, Lee SS, Seo DW, Lee SK, Kim MH. Similar Efficacies of Endoscopic Ultrasound-guided Transmural and Percutaneous Drainage for Malignant Distal Biliary Obstruction. Clin Gastroenterol Hepatol. 2016 Jul;14(7):1011-1019.e3. doi: 10.1016/j.cgh.2015.12.032. Epub 2015 Dec 31. — View Citation

Liu YS, Lin CY, Chuang MT, Tsai YS, Wang CK, Ou MC. Success and complications of percutaneous transhepatic biliary drainage are influenced by liver entry segment and level of catheter placement. Abdom Radiol (NY). 2018 Mar;43(3):713-722. doi: 10.1007/s00261-017-1258-5. — View Citation

Schmitz D, Grosse A, Hallscheidt P, Roseneck A, Niemeyer J, Rudi J. Color Doppler ultrasound-guided PTBD with and without metal stent implantation by endoscopic control: prospective success and early adverse event rates. Z Gastroenterol. 2015 Nov;53(11):1255-60. doi: 10.1055/s-0041-104225. Epub 2015 Nov 12. — View Citation

Sharaiha RZ, Khan MA, Kamal F, Tyberg A, Tombazzi CR, Ali B, Tombazzi C, Kahaleh M. Efficacy and safety of EUS-guided biliary drainage in comparison with percutaneous biliary drainage when ERCP fails: a systematic review and meta-analysis. Gastrointest Endosc. 2017 May;85(5):904-914. doi: 10.1016/j.gie.2016.12.023. Epub 2017 Jan 4. — View Citation

Sharaiha RZ, Kumta NA, Desai AP, DeFilippis EM, Gabr M, Sarkisian AM, Salgado S, Millman J, Benvenuto A, Cohen M, Tyberg A, Gaidhane M, Kahaleh M. Endoscopic ultrasound-guided biliary drainage versus percutaneous transhepatic biliary drainage: predictors of successful outcome in patients who fail endoscopic retrograde cholangiopancreatography. Surg Endosc. 2016 Dec;30(12):5500-5505. doi: 10.1007/s00464-016-4913-y. Epub 2016 Apr 29. — View Citation

Sportes A, Camus M, Greget M, Leblanc S, Coriat R, Hochberger J, Chaussade S, Grabar S, Prat F. Endoscopic ultrasound-guided hepaticogastrostomy versus percutaneous transhepatic drainage for malignant biliary obstruction after failed endoscopic retrograde cholangiopancreatography: a retrospective expertise-based study from two centers. Therap Adv Gastroenterol. 2017 Jun;10(6):483-493. doi: 10.1177/1756283X17702096. Epub 2017 Apr 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Clinical success	Decrease of bilirubin level on more than a half of the initial value	7 days after the intervention
Secondary	Adverse events	All adverse events caused by the intervention	Up to 30 days after the intervention
Secondary	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
Secondary	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
Secondary	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.
Secondary	Survival time	Time from the day of intervention to the death of the patient	Follow up of six months