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NCT Number: NCT07817602

Real-world Evaluation of Different Endoscopic Biliary Drainage Techniques in Patients With Jaundice of Biliopancreatic Malignant Origin

The incidence of pancreatic cancer is rising. Tumor-induced obstruction of the distal bile duct is a common complication, occurring during the course of nearly 80% of pancreatic tumors. Approximately 10% of these obstructions are complicated by cholangitis, and jaundice is associated with tumor progression due to the resulting impairment of cellular immunity. The standard treatment for distal bile duct obstruction is transpapillary drainage via endoscopic retrograde cholangiopancreatography (ERCP). This procedure is performed under general anesthesia and carries a failure rate of 15% and a complication rate of up to 9%. In recent years, alternative techniques for endoscopic ultrasound (EUS)-guided biliary drainage have been developed, such as hepaticogastrostomy, choledochoduodenostomy, and cholecystogastrostomy. These EUS-guided biliary drainage techniques overcome failures caused by malignant duodenal stenosis (present in up to 25% of such cases), with lower morbidity and greater clinical efficacy compared to percutaneous radiological drainage. EUS-guided biliary drainage techniques have been simplified by the advent of lumen-apposing metal stents (LAMS), which have enabled technical success rates of nearly 90%. The two techniques most frequently described in the literature are choledochoduodenostomy (CDS)-connecting the common bile duct to the duodenal bulb-and hepaticogastrostomy (HGS)-connecting the left intrahepatic bile ducts to the stomach. CDS is less morbid and technically easier to perform but has limitations in cases of duodenal stenosis, an insufficiently dilated common bile duct, or an unfavorable puncture window. For a long time, endoscopic gallbladder drainage via cholecystogastrostomy (CGS) was restricted to treating acute cholecystitis in patients ineligible for surgery; its use for biliary drainage in cases of malignant jaundice remained anecdotal, for reasons that were not clearly identified. The investigators were the first to publish a multicenter comparative study contrasting CGS with CDS following failed ERCP for distal malignant biliary obstruction. This study demonstrated comparable technical and clinical success rates for both techniques, with a better long-term morbidity profile favoring CGS. More recently, a large-scale international multicenter study validated the efficacy of gallbladder drainage compared to common bile duct drainage as a first-line approach. The study team previously launched the COPPINE cohort (Prospective Cohort of Innovative Endoscopic Procedures) in 2024, aiming to continuously enroll all patients undergoing innovative endoscopic procedures, including endoscopic ultrasound-guided biliary drainage. This study aims to prospectively compare the clinical outcomes of patients with malignant distal biliary obstruction based on the biliary drainage technique they received.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

CHU Dupuytren, Limoges, France

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Distal biliary obstruction of malignant etiology (pancreas, ampulloma, compressive metastatic lymphadenopathy, other distal tumors).
  • Decision made to proceed with biliary drainage.
  • Patient informed and no objection raised, in accordance with the MR-004 framework and COPPINE procedure

Exclusion criteria

  • The subject is participating in another study
  • The subject unable to expression on-objection
  • It is impossible to give the subject informed information
  • The patient is under safeguard of justice or state guardianship
  • Proximal/hilar or benign obstruction (non-tumoral lesions).
  • Contraindication to endoscopy/anesthesia (uncorrectable hemodynamic instability, uncontrolled coagulation disorders, etc.).
  • History of prior biliary drainage.
  • Pregnant or breastfeeding patient.

Treatment and study plan

endoscopic drainage

Procedure

Choice of modalities: ERCP, EUS-guided gallbladder drainage (EUS-GBD), EUS-guided choledochoduodenostomy (EUS-CDS), and EUS-guided hepaticogastrostomy (EUS-HGS)

Primary outcomes

  1. Biliary stent dysfunction between different endoscopic drainage modalities

    Time frame: Month 12

    Yes/no, according to Guidelines on Reporting Outcomes in Biliary Drainage Trials

Secondary outcomes

  1. Technical success rate of biliary stent placement with immediate visualization of biliary flow during the procedure between different endoscopic drainage modalities

    Time frame: Month 12

    Yes/no, where stent malposition or incomplete deployment requiring conversion or rescue maneuvers will not be considered technical successes.

  2. Clinical success

    Time frame: Month 12

    Yes/no, measured as reduction of ≥50% in total bilirubin level compared to the pre-procedural value within 2 weeks of the index procedure, or achieving a total bilirubin level of less than 25% of the pre-procedural value within 6 weeks

  3. Use of advanced cannulation techniques versus endoscopic ultrasound (EUS)-guided techniques in cases of difficult ERCP

    Time frame: Month 12

    Yes/no for use of: double-guidewire technique, precut, infundibulotomy, other

  4. Segment showing highest drainage efficacy

    Time frame: Month 12

    Segment (II or III) with best bilirubin levels (µmol/L)

  5. Tumor stage

    Time frame: Month 12

    TNM staging

  6. Tumor size

    Time frame: Month 12

    cm

  7. Tumor invasion of the cystic-common bile duct junction

    Time frame: Month 12

    Yes/no

  8. Distance between the tumor and the cystic-common bile duct junction

    Time frame: Month 12

    mm

  9. Physician experience

    Time frame: Month 12

    Classed as: resident, senior registrar/assistant, junior attending (<500 procedures), or experienced attending (>500 procedures)

  10. Location of stenosis

    Time frame: Month 12

    Classed as: pylorus, D1, D2, D3, D4, jejunum, or multiple segments

  11. length of stenosis

    Time frame: Month 12

    cm

  12. tumor invasion of the papilla

    Time frame: Month 12

    yes/no

  13. Clinical success rate

    Time frame: Month 12

    Yes/no, where success is classed as ≥50% reduction in total bilirubin levels compared to the pre-procedural value within 2 weeks of the index procedure, or achieving a total bilirubin level below 25% of the pre-procedural value within 6 weeks.

  14. Bilirubin levels

    Time frame: Day 0, Day 14, Day 45, Month 6, and Month 12.

    µmol/l

  15. New biliary drainage procedure

    Time frame: Month 12

    Yes/no

  16. Interval between the 1st and 2nd procedure if necessary

    Time frame: Month 12

    Days

  17. Re-intervention strategy/types of re-intervention

    Time frame: Month 12

    Classed as: ERCP, HGS, CGS, CDS, radiological drainage

  18. Time to initiation of chemotherapy

    Time frame: Month 12

    Measured from day of the endoscopic procedure and Day 1 of chemotherapy

  19. Proportion of patients with a surgical plan

    Time frame: Month 12

    Yes/no

  20. Proportion of patients with a chemotherapy plan

    Time frame: Month 12

    Yes/no

  21. Proportion of patients with a palliative care plan

    Time frame: Month 12

    Yes/no

  22. Proportion of patients for whom surgery performed

    Time frame: Month 12

    Yes/no

  23. Proportion of patients for whom chemotherapy performed

    Time frame: Month 12

    Yes/no

  24. surgical complication related to the prior endoscopic procedure

    Time frame: Month 12

    Yes/no

  25. Technique used in cases of duodenal stenosis

    Time frame: Month 12

    Classed as: ERCP, HGS, CDS, CGS, radiological drainage

  26. CGS drainage technique

    Time frame: Month 12

    Classed as cholecystogastric or cholecystoduodenal

  27. Cumulative incidence of adverse events

    Time frame: Month 12

    Number

  28. Timing of adverse events

    Time frame: Month 12

    Classed as: early: <30 days; late: ≥30 days

  29. Causality of adverse events

    Time frame: Month 12

    Classed as: procedure-related, disease-related, or unrelated

  30. Severity of adverse events

    Time frame: Month 12

    According to the AGREE classification (grades I to V) and the ASGE lexicon (Nass et al. 2022); - Specifically reported adverse events will include: cholangitis, bile leak, hemorrhage, pneumoperitoneum, perforation, stent migration, stent occlusion, cholecystitis (EUS-GBD arm), and buried stent syndrome. Chemotherapy interruption directly attributable to a drainage-related event will be documented as an indirect adverse event.

  31. Overall survival between different endoscopic drainage modalities

    Time frame: Month 12

  32. Survival free from biliary re-intervention between different endoscopic drainage modalities

    Time frame: Month 12

  33. Mean total cost per patient

    Time frame: Month 12

    Including the initial procedure, expressed in euros; calculated from the perspective of the healthcare system (hospitals + health insurance) and including the costs of hospitalizations, transport, and endoscopic procedures (initial procedure and any re-interventions).

  34. Proportion of operable or borderline patients who were surgically explored

    Time frame: Month 12

    Defined as the actual performance of a laparotomy or laparoscopy with the aim of pancreatic resection

  35. Proportion of operable or borderline patients who were resected

    Time frame: Month 12

    Defined as the performance of a pancreatic resection procedure

  36. Need for an associated vascular procedure

    Time frame: Month 12

    yes/no (including venous or arterial resection and/or reconstruction)

  37. Conversion to laparotomy in patients initially operated on via a minimally invasive approach

    Time frame: Month 12

    Yes/no

  38. Margin status

    Time frame: Month 12

    Resection margin status: R0 / R1

  39. Lymph node dissection

    Time frame: Month 12

    Number of lymph nodes analyzed: continuous quantitative variable (absolute number)

  40. Postoperative pathological stage (ypTNM)

    Time frame: Month 12

    measured according to the classification in effect at the time of surgery

  41. Presence of severe morbidity

    Time frame: Month 12

    Occurrence of at least one severe postoperative complication, defined as: Clavien-Dindo ≥ III

  42. 30-day mortality

    Time frame: Day 30

    Yes/no

  43. 90-day mortality

    Time frame: Day 90

    Yes/no

  44. Feasibility rate

    Time frame: Month 24

    Percentage of centers that enrolled at least 5 patients within the scheduled timeframe

  45. Enrollment rate for eligible patients

    Time frame: Month 12

    Calculated as: number of patients enrolled / number of eligible patients identified

  46. Data completeness rate for the minimum variables required for the future registry

    Time frame: Month 24

    Percentage

Study contacts

Contact information is provided by the study sponsor or research team.

Ludovic Caillo

CONTACT

[email protected]

06.70.88.85.07

Sponsors and collaborators

Lead sponsor

Centre Hospitalier Universitaire de Nīmes

Other

Registry information

Acronym: PROBILEUS

Important dates

Study start
2026
Primary completion
2028
Study completion
2028
First posted
Sep 14, 2026
Registry last updated
Sep 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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