EUS-guided Choledochoduodenostomy vs ERCP as First Line in Malignant Distal Obstruction in Resectable Disease (CARPEDIEM-1 Trial)

Endoscopic Ultrasound-Guided Biliary Drainage With Lumen-Apposing Stent vs Classical ERCP for First-line Therapy of Malignant Distal Biliary Obstruction in Resectable Disease: An Open-label, Multicenter Randomized Controlled Trial (CARPEDIEM-1 Trial)

The aim of this clinical trial is to evaluate temporal delay (days) between biliary drainage (EUS-CDS vs ERCP as first line therapy) and surgery in patients with resectable distal malignant biliary obstruction.

Study Overview

• Status: Not yet recruiting
• Conditions: Biliary Tract Neoplasms; Pancreatic Cancer Resectable; Malignant Biliary Obstruction
• Intervention / Treatment: Procedure: Endoscopic biliary drainage; Device: Lumen-apposing metal stent (LAMS) and double-pigtail plastic stent (DPPS); Device: Self-expandable metallic stent (SEMS)

Detailed Description

Ecoendoscopy-guided choledochoduodenostomy (EUS-CDS) has been extended as a second line treatment in cases of ERCP failure in malignant distal biliary obstruction (MDBO). However, there are clinical trials which have compared it with ERCP as a first line treatment for MDBO in palliative patients, showing similar clinical and technical success and adverse events (AEs) rate between both techniques. Data about the benefit of this techique in resectable patients is still limited.

A recent retrospective study (Janet J et al, Ann Surg Oncol 2023) which included resectable patients, found that EUS-CDS group had significantly less delay (days) between biliary drainage and surgery than the ERCP group, with fewer endoscopy and surgery AEs.

Thus, our hypothesis is that EUS-CDS has benefits in terms of decreasing delay between biliary drainage when compared to ERCP in MDBO in resectable patients.

• Study Type: Interventional
• Enrollment (Estimated): 44
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Maria Puigcerver-Mas, MD, Research fellow; Phone Number: +34687332007; Email: mariapuigcervermas@gmail.com
• Study Contact Backup: Name: Joan B Gornals, PhD; Phone Number: 2624 +34932607682; Email: jgornals@bellvitgehospital.cat

Study Locations

• Spain
  • Barcelona, Catalonia
    • L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain, 08907
      • Hospital Universitari de Bellvitge
      • Contact: Joan B Gornals, MD, PhD; Phone Number: 2624 +34 93 260 76 82; Email: jgornals@bellvitgehospital.cat
      • Sub-Investigator: Sandra Maisterra, MD
      • Principal Investigator: Carme Loras, MD, PhD
      • Principal Investigator: Charly Guarner Argente, MD, PHD
      • Principal Investigator: Juan J Vila, MD, PhD
      • Principal Investigator: Jose Lariño, MD, PhD
      • Principal Investigator: Vicente Sanchiz, MD, PhD
      • Contact: Maria Puigcerver-Mas, MD; Phone Number: +34 687332007; Email: mariapuigcervermas@gmail.com
      • Sub-Investigator: Berta Laquente, MD, PhD
      • Sub-Investigator: Juli Busquets, MD, PhD
      • Principal Investigator: Eduardo Redondo, MD, PhD
      • Sub-Investigator: Julia Escuer-Turu, MD
      • Sub-Investigator: Daniel Luna Rodriguez, MD
      • Sub-Investigator: Albert Sumalla, MD
      • Sub-Investigator: Julio Velasquez Rodriguez, MD
      • Principal Investigator: Rafael Pedraza, MD
      • Principal Investigator: Jose Ramon Aparicio, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Malignant distal biliary obstruction diagnosed in patient considered RESECTABLE with biliary drainage indication: i) impaired hepatic enzymes (including hyperbilirubinemia) x3 times upper the superior normal value. ii) Radiologic singns of extrahepatic bile duct obstruction with presence of retrograde dilatation, of at least 12-mm axial diameter.
• Consensual malignancy by a bilio-pancreatic multidisciplinar committe (histological confirmation is not mandatory)
• Patient capable of understanding and/or singning the informed consent.
• Patient who understands the type of study and will comply with all follow-up tests throughout its duration

Exclusion Criteria:

• Pregnancy or lactation.
• Severe coagulation disorder: INR > 1.5 non correctable with plasma administration and/or platelet count < 50.000/mm3.
• Distal malignant biliary strictures in patients considered borderline, non-surgical, unresectable, or palliative
• Benign or uncertain etiology of biliary strictures or strictures located proximally or in close proximity to the hilum.
• Patients with prior biliary stents or other biliary drainages (e.g., PTCD).
• Altered intestinal anatomy due to prior surgery that prevents or hinders papillary access (e.g., gastric bypass, Billroth II, duodenal switch, Roux-en-Y).
• Stenosis in the antral or duodenal region that prevents access to the duodenum and reaching the papilla.
• Situations that do not allow for upper gastrointestinal endoscopy (e.g., esophageal stricture).
• Patients with functional diversity, who lack the capacity to understand the nature and potential consequences of the study, except when a legal representative is available.
• Patients incapable of maintaining follow-up appointments (lack of adherence).
• Lack of informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ERCP with SEMS; Endoscopic retrograde cholangiopancreatography (ERCP) with deployment of a self-expandable metallic stent (SEMS). Gold standard in malignant distal biliary obstruction (MDBO) in current practice. ERCP technique: Cannulation with papillotome (advanced cannulation techniques are allowed). Sphincterotomy. Self-expandable metallic stent (SEMS) deployment.	Procedure: Endoscopic biliary drainage; Decompression of the bile duct by endoscopic aproach.; Other Names: Biliary drainage; Device: Self-expandable metallic stent (SEMS); Self-expandable metallic stent (SEMS) deployment: Covering: Uncovered or Partially Covered. Non covered if gallbladder is present.; Size: 10x40mm or 10x60mm or 10x80mm.
Experimental: EUS-CDS with LAMS-Pigtail; Echoendoscopy-guided Choledochoduodenostomy (EUS-CDS) with deployment of a lumen-apposing metal stent (LAMS) and axis-orienting double-pigtail plastic stent throug LAMS. EUS-CDS technique: Diagnostic EUS. Classic or free-hand with preloaded guidewire choledochoduodenostomy with LAMS. Pneumatic dilation whithin LAMS is allowed. In case of bile duct < 15mm is mandatory the 'push' technique. Deployment of a pigtail coaxial to LAMS.	Procedure: Endoscopic biliary drainage; Decompression of the bile duct by endoscopic aproach.; Other Names: Biliary drainage; Device: Lumen-apposing metal stent (LAMS) and double-pigtail plastic stent (DPPS); Lumen-apposing metal stent (LAMS) with coaxial double-pigtail plastic stent (DPPS) deployment: LAMS size: 6x8mm or 8x8mm. Consider 10x10mm if bile duct > 18mm.; DPPS size: 7Fr x 3-7cm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delay in days between endoscopic biliary drainage and cephalic duodenopancreatectomy (CDP)	Number of days between intervention (T1-biliary drainage) and surgery.	1 day to 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AE - biliary drainage	Adverse events rate related to biliary drainage according to the AGREE classification	0 to 30 days after BD
AE - surgery	Adverse events rate related to surgery according to the Claiven and Dindo classification.	0 to 90 days after surgery
Technical success	ERCP group: cannulation, cholangiogram, correct deployment of SEMS. EUS-CDS group: Correct deployment of both flaps of LAMS (and pigtail) in place, checked by ecoendoscopy/endoscopic image/floroscopy.	day 0
Clinical success	In jaundice: decreasing > 50% of bilirrubin or normalization of bilirrubin levels 14 days after endoscopic procedure. In cholangitis: stop of antibiotics without clinical recurrence or decreasing > 50% of acute phase reactants 14 days after the endoscopic procedure.	14 days after BD

Collaborators and Investigators

• Sponsor: Hospital Universitari de Bellvitge
• Collaborators: Hospital Universitario Ramon y Cajal; Complejo Hospitalario de Navarra; University of Salamanca; Hospital Mutua de Terrassa; Hospital General Universitario de Alicante; Complejo Hospitalario Universitario de Santiago; Hospital de Sant Pau; Hospital Álvaro Cunqueiro; University Hospital Virgen de las Nieves; Hospital General Universitario de Castellón; Hospital Clínico Universitario de Valencia
• Investigators: Principal Investigator: Joan B Gornals, PhD, Bellvitge University Hospital

Publications and helpful links

General Publications

• Teoh AYB, Napoleon B, Kunda R, Arcidiacono PG, Kongkam P, Larghi A, Van der Merwe S, Jacques J, Legros R, Thawee RE, Saxena P, Aerts M, Archibugi L, Chan SM, Fumex F, Kaffes AJ, Ma MTW, Messaoudi N, Rizzatti G, Ng KKC, Ng EKW, Chiu PWY. EUS-Guided Choledocho-duodenostomy Using Lumen Apposing Stent Versus ERCP With Covered Metallic Stents in Patients With Unresectable Malignant Distal Biliary Obstruction: A Multicenter Randomized Controlled Trial (DRA-MBO Trial). Gastroenterology. 2023 Aug;165(2):473-482.e2. doi: 10.1053/j.gastro.2023.04.016. Epub 2023 Apr 28.
• Janet J, Albouys J, Napoleon B, Jacques J, Mathonnet M, Magne J, Fontaine M, de Ponthaud C, Durand Fontanier S, Bardet SSM, Bourdariat R, Sulpice L, Lesurtel M, Legros R, Truant S, Robin F, Prat F, Palazzo M, Schwarz L, Buc E, Sauvanet A, Gaujoux S, Taibi A. Pancreatoduodenectomy Following Preoperative Biliary Drainage Using Endoscopic Ultrasound-Guided Choledochoduodenostomy Versus a Transpapillary Stent: A Multicenter Comparative Cohort Study of the ACHBT-FRENCH-SFED Intergroup. Ann Surg Oncol. 2023 Aug;30(8):5036-5046. doi: 10.1245/s10434-023-13466-8. Epub 2023 Apr 17.
• Paik WH, Lee TH, Park DH, Choi JH, Kim SO, Jang S, Kim DU, Shim JH, Song TJ, Lee SS, Seo DW, Lee SK, Kim MH. EUS-Guided Biliary Drainage Versus ERCP for the Primary Palliation of Malignant Biliary Obstruction: A Multicenter Randomized Clinical Trial. Am J Gastroenterol. 2018 Jul;113(7):987-997. doi: 10.1038/s41395-018-0122-8. Epub 2018 Jul 2. Erratum In: Am J Gastroenterol. 2018 Oct;113(10):1566.
• Bang JY, Hawes R, Varadarajulu S. Endoscopic biliary drainage for malignant distal biliary obstruction: Which is better - endoscopic retrograde cholangiopancreatography or endoscopic ultrasound? Dig Endosc. 2022 Jan;34(2):317-324. doi: 10.1111/den.14186. Epub 2021 Nov 29.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: April 16, 2024
• First Submitted That Met QC Criteria: April 18, 2024
• First Posted (Actual): April 19, 2024

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: ERCP; Therapeutic endoscopy; Lumen apposing metal stent; Biliary Drainage; Choledochoduodenostomy; Biliopancreatic maliognancy
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms
• Other Study ID Numbers: CARPEDIEM-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes