Clinical trial NCT03546049: Ultrasound-guided Percutaneous Biliary Drainage Versus Endoscopic Ultrasound-guided Biliary Drainage
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Bile Duct Obstruction, Extrahepatic
Keywords: 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
Lead sponsor: Theresienkrankenhaus und St. Hedwig-Klinik GmbH
Sponsor class: OTHER
Collaborators: name: University Hospital Heidelberg
First posted: 2018-06-06
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: prospective, non-randomized multicenter study (each center performs the intervention which can do best)
Primary purpose: TREATMENT

Brief 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)

Detailed 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).

Eligibility criteria: 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

Primary outcomes:
measure: Technical success
timeFrame: 1 minute after injection of a radiocontrast agent into the expanded metal stent
Secondary outcomes:
measure: Clinical success
timeFrame: 7 days after the intervention
measure: Adverse events
timeFrame: Up to 30 days after the intervention
measure: Re-interventions
timeFrame: 6 months after successful implantation of the metal stent
measure: Duration of the procedure
timeFrame: The day of the performed procedure (24 h), usually from 10 minutes up to 180 minutes
measure: Length of hospital stay
timeFrame: 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.
measure: Survival time
timeFrame: Follow up of six months
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: Tertiary referral hospital: Theresienkrankenhaus und St. Hedwig Hospital
Study officials:
affiliation: Institut für Medizinische Biometrie und Informatik Abteilung Medizinische Biometrie, Heidelberg University Hospital
name: Anja Sander, Dr.M.Sc.
role: STUDY_DIRECTOR
References:
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.
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citation: 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.
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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.
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.
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.
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.
citation: Schmitz D, Valiente CT, Dollhopf M, Perez-Miranda M, Kullmer A, Gornals J, Vila J, Weigt J, Voigtlander T, Redondo-Cerezo E, von Hahn T, Albert J, Vom Dahl S, Beyna T, Hartmann D, Franck F, Garcia-Alonso FJ, Schmidt A, Garcia-Sumalla A, Arrubla A, Joerdens M, Kleemann T, Tomo JRA, Grassmann F, Rudi J. Percutaneous transhepatic or endoscopic ultrasound-guided biliary drainage in malignant distal bile duct obstruction using a self-expanding metal stent: Study protocol for a prospective European multicenter trial (PUMa trial). PLoS One. 2022 Oct 27;17(10):e0275029. doi: 10.1371/journal.pone.0275029. eCollection 2022.