Removable Intraductal Stenting in Duct-to-duct Biliary Reconstruction in Liver Transplantation

Transplantation, Liver Clinical Trial

— BILIDRAINT  

Official title:

Efficacy Of A Removable Intraductal Stent In Duct-To-Duct Biliary Reconstruction To Prevent Biliary Complications In Liver Transplantation: A Randomized Controlled Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02356939
• Other study ID #: P 130919
• Status: Terminated
• Phase: N/A
• Start date: April 3, 2015
• Est. completion date: May 22, 2019

Study information

• Verified date: October 2021
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Randomized controlled trial including 7 French transplantation centers. Pre-inclusion of the patients is made when enlisted for liver transplantation (LT). Definitive inclusion and randomization is performed during LT, for patients undergoing a duct-to-duct biliary anastomosis with a graft bile duct diameter smaller than 7mm. In the intraductal stent tube group, a custom-made segment of a T-tube is placed into the bile duct, and removed endoscopically four to six months postoperative. The surgical technique is available on a movie during randomization on the website. The primary endpoint is the occurrence of biliary complications, including biliary fistulae and strictures, during six months of follow-up. Secondary evaluation criteria are the incidence of complications related to the stent placement and its extraction by endoscopy.

Discussion: Biliary complications following LT are significant causes of morbidity, retransplantation and eventually mortality. Although controversial, the use of a T-tube has been proven to be useless and even responsible for specific complications in many studies, including several randomized trials. However, several studies have identified a small bile duct diameter as a risk factor for biliary stenosis. A threshold of 7mm was found to be significantly associated to biliary stenosis. Our team published a preliminary study including 20 patients using a new technique of intraductal stenting. Only 4 complications were reported in the overall study population while no biliary complication occurred in the subgroup of patients who received a whole graft LT. Moreover, no technical failure and no procedure-related complications were noted before and during drain removal. Although intraductal stent tube in duct-to duct biliary anastomosis seems feasible and safe, a multicentric randomized controlled study is needed to validate it as a protective tool for biliary complications following LT.

Description:

Comparative, multicentric, prospective, randomized non-blinded, two-groups study.

The follow-up is set at six months postoperative for a good screening of the majority of biliary complications.

The inclusion period is set at 3.5 years, for total study duration of 4 years. The patients' inclusion will be made in 7 liver transplantation centers in France.

Patients' inclusion will be performed in consultation at the moment of enlistment for LT, where they will be informed of the content, the benefits and risks of the study, and have to sign a written consent.

Definitive inclusion will be performed in operating room, during LT, and depends on fulfilling of the following "definitive inclusion criteria" (see above).

The randomization will be performed in operating room by the investigator and coordinated by the Clinical Research Unit of promoters' center (Saint Antoine Hospital, Paris), with a specific software accessible on the Internet.

In the IST group, the surgeon will place the IST in the bile duct, which is a custom-made segment (2 cm) of a 8 French T-tube with no side holes. The stent is inserted in the biliary duct without suture fixation.

In order to minimize bias and to homogenize the technique, a short technical explanatory movie will be realized by the promoter's team and distributed in each center.

Each center will perform its habitual postoperative follow up. Clinical, biological, and radiological exhaustive data will be collected at Day 1, Day 7, Day 15, Month 1, Month 3, Month 6.

A Magnetic Resonance Cholangiography (MRC) will be systematically performed at six months post LT.

In the IST group, an endoscopic retrograde cholangio-pancreatography (ERCP) with sphincterotomy will be planned between the 4th and the 5th month post-transplantation, requiring a short stay in hospital, a general anesthesia, clinical and biological tests including plasmatic lipase dosage at Day 1.

Every undesirable event will be immediately reported to the promoter for further investigation within its severity. Severe undesirable events will be previously defined.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 493
• Est. completion date: May 22, 2019
• Est. primary completion date: May 22, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients eligible for a liver transplantation

• Patients' written informed consent signed

• Patient with social coverage (excepting AME)

Exclusion criteria:

• Biliary reconstruction decided to be a hepaticojejunostomy for anatomical/biliary disease reason

• Non eligibility for liver transplantation:

1. - Uncontrolled infectious process

2. - Incompatible physical or mental state with the observance of the immunosuppressive drugs

3. - Cardiopulmonary comorbidities severe / uncontrolled

4. - Active alcohol intoxication or addiction

5. - Pregnant or breastfeeding women (pregnancy test will be performed at baseline)

• Latex Allergy, polymer or rubber

• Patient participating in another interventional study about biliary disease

Related Conditions & MeSH terms

• Transplantation, Liver

Intervention

Device:
• intraductal removable stent custom-made segment (2 cm)
: In the IST group, the surgeon will place the IST in the bile duct, which is a custom-made segment (2 cm) of a 8 French T-tube. The stent is inserted in the biliary duct without suture fixation. In order to minimize bias and to homogenize the technique, a short technical explanatory movie was realized by the promoter's team and edited on internet. In the IST group, an endoscopic retrograde cholangio-pancreatography (ERCP) with sphincterotomy will be planned between the 4th and the 5th month post-transplantation, requiring a short stay in hospital, a general anesthesia, clinical and biological tests including plasmatic lipase dosage at Day 1.

Procedure:
• stent extraction by ERCP
stent extraction by endoscopic retrograde cholangio-pancreatography

Locations

Country	Name	City	State
France	Hôpital Pitié Salpétrière	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (28)

Akamatsu N, Sugawara Y, Hashimoto D. Biliary reconstruction, its complications and management of biliary complications after adult liver transplantation: a systematic review of the incidence, risk factors and outcome. Transpl Int. 2011 Apr;24(4):379-92. doi: 10.1111/j.1432-2277.2010.01202.x. Epub 2010 Dec 10. Review. — View Citation

Ben-Ari Z, Neville L, Davidson B, Rolles K, Burroughs AK. Infection rates with and without T-tube splintage of common bile duct anastomosis in liver transplantation. Transpl Int. 1998;11(2):123-6. — View Citation

CATTELL RB, BRAASCH JW. An eveluation of the long T-tube. Ann Surg. 1961 Aug;154:252-4. — View Citation

Chaput U, Scatton O, Bichard P, Ponchon T, Chryssostalis A, Gaudric M, Mangialavori L, Duchmann JC, Massault PP, Conti F, Calmus Y, Chaussade S, Soubrane O, Prat F. Temporary placement of partially covered self-expandable metal stents for anastomotic biliary strictures after liver transplantation: a prospective, multicenter study. Gastrointest Endosc. 2010 Dec;72(6):1167-74. doi: 10.1016/j.gie.2010.08.016. — View Citation

Consensus conference: Indications for Liver Transplantation, January 19 and 20, 2005, Lyon-Palais Des Congrès: text of recommendations (long version). Liver Transpl. 2006 Jun;12(6):998-1011. — View Citation

Cotton PB, Garrow DA, Gallagher J, Romagnuolo J. Risk factors for complications after ERCP: a multivariate analysis of 11,497 procedures over 12 years. Gastrointest Endosc. 2009 Jul;70(1):80-8. doi: 10.1016/j.gie.2008.10.039. Epub 2009 Mar 14. — View Citation

Duailibi DF, Ribeiro MA Jr. Biliary complications following deceased and living donor liver transplantation: a review. Transplant Proc. 2010 Mar;42(2):517-20. doi: 10.1016/j.transproceed.2010.01.017. Review. — View Citation

Farhat S, Bourrier A, Gaudric M, Dousset B, Scatton O, Chaussade S, Prat F. Endoscopic treatment of biliary fistulas after complex liver resection. Ann Surg. 2011 Jan;253(1):88-93. doi: 10.1097/SLA.0b013e3181f9b9f0. — View Citation

Gastaca M. Biliary complications after orthotopic liver transplantation: a review of incidence and risk factors. Transplant Proc. 2012 Jul-Aug;44(6):1545-9. doi: 10.1016/j.transproceed.2012.05.008. Review. — View Citation

Hwang S, Lee SG, Sung KB, Park KM, Kim KH, Ahn CS, Lee YJ, Lee SK, Hwang GS, Moon DB, Ha TY, Kim DS, Jung JP, Song GW. Long-term incidence, risk factors, and management of biliary complications after adult living donor liver transplantation. Liver Transpl. 2006 May;12(5):831-8. — View Citation

Jain A, Reyes J, Kashyap R, Dodson SF, Demetris AJ, Ruppert K, Abu-Elmagd K, Marsh W, Madariaga J, Mazariegos G, Geller D, Bonham CA, Gayowski T, Cacciarelli T, Fontes P, Starzl TE, Fung JJ. Long-term survival after liver transplantation in 4,000 consecutive patients at a single center. Ann Surg. 2000 Oct;232(4):490-500. — View Citation

López-Andújar R, Orón EM, Carregnato AF, Suárez FV, Herraiz AM, Rodríguez FS, Carbó JJ, Ibars EP, Sos JE, Suárez AR, Castillo MP, Pallardó JM, De Juan Burgueño M. T-tube or no T-tube in cadaveric orthotopic liver transplantation: the eternal dilemma: results of a prospective and randomized clinical trial. Ann Surg. 2013 Jul;258(1):21-9. doi: 10.1097/SLA.0b013e318286e0a0. — View Citation

Marubashi S, Dono K, Nagano H, Kobayashi S, Takeda Y, Umeshita K, Monden M, Doki Y, Mori M. Biliary reconstruction in living donor liver transplantation: technical invention and risk factor analysis for anastomotic stricture. Transplantation. 2009 Nov 15;88(9):1123-30. doi: 10.1097/TP.0b013e3181ba184a. — View Citation

National Institutes of Health Consensus Development Conference Statement: liver transplantation--June 20-23, 1983. Hepatology. 1984 Jan-Feb;4(1 Suppl):107S-110S. — View Citation

Neuhaus P, Blumhardt G, Bechstein WO, Steffen R, Platz KP, Keck H. Technique and results of biliary reconstruction using side-to-side choledochocholedochostomy in 300 orthotopic liver transplants. Ann Surg. 1994 Apr;219(4):426-34. — View Citation

Ostroff JW. Post-transplant biliary problems. Gastrointest Endosc Clin N Am. 2001 Jan;11(1):163-83. Review. — View Citation

Park JB, Kwon CH, Choi GS, Chun JM, Jung GO, Kim SJ, Joh JW, Lee SK. Prolonged cold ischemic time is a risk factor for biliary strictures in duct-to-duct biliary reconstruction in living donor liver transplantation. Transplantation. 2008 Dec 15;86(11):1536-42. doi: 10.1097/TP.0b013e31818b2316. — View Citation

Roberts MS, Angus DC, Bryce CL, Valenta Z, Weissfeld L. Survival after liver transplantation in the United States: a disease-specific analysis of the UNOS database. Liver Transpl. 2004 Jul;10(7):886-97. — View Citation

Rolles K, Dawson K, Novell R, Hayter B, Davidson B, Burroughs A. Biliary anastomosis after liver transplantation does not benefit from T tube splintage. Transplantation. 1994 Feb;57(3):402-4. — View Citation

Scatton O, Meunier B, Cherqui D, Boillot O, Sauvanet A, Boudjema K, Launois B, Fagniez PL, Belghiti J, Wolff P, Houssin D, Soubrane O. Randomized trial of choledochocholedochostomy with or without a T tube in orthotopic liver transplantation. Ann Surg. 2001 Mar;233(3):432-7. — View Citation

Shaked A. Use of T tube in liver transplantation. Liver Transpl Surg. 1997 Sep;3(5 Suppl 1):S22-3. Review. — View Citation

Sharma S, Gurakar A, Jabbour N. Biliary strictures following liver transplantation: past, present and preventive strategies. Liver Transpl. 2008 Jun;14(6):759-69. doi: 10.1002/lt.21509. — View Citation

Sherman S, Jamidar P, Shaked A, Kendall BJ, Goldstein LI, Busuttil RW. Biliary tract complications after orthotopic liver transplantation. Endoscopic approach to diagnosis and therapy. Transplantation. 1995 Sep 15;60(5):467-70. — View Citation

Tranchart H, Zalinski S, Sepulveda A, Chirica M, Prat F, Soubrane O, Scatton O. Removable intraductal stenting in duct-to-duct biliary reconstruction in liver transplantation. Transpl Int. 2012 Jan;25(1):19-24. doi: 10.1111/j.1432-2277.2011.01339.x. Epub 2011 Sep 29. — View Citation

Vandenbroucke F, Plasse M, Dagenais M, Lapointe R, Lêtourneau R, Roy A. Treatment of post liver transplantation bile duct stricture with self-expandable metallic stent. HPB (Oxford). 2006;8(3):202-5. doi: 10.1080/13651820500501800. — View Citation

Vougas V, Rela M, Gane E, Muiesan P, Melendez HV, Williams R, Heaton ND. A prospective randomised trial of bile duct reconstruction at liver transplantation: T tube or no T tube? Transpl Int. 1996;9(4):392-5. — View Citation

Weiss S, Schmidt SC, Ulrich F, Pascher A, Schumacher G, Stockmann M, Puhl G, Guckelberger O, Neumann UP, Pratschke J, Neuhaus P. Biliary reconstruction using a side-to-side choledochocholedochostomy with or without T-tube in deceased donor liver transplantation: a prospective randomized trial. Ann Surg. 2009 Nov;250(5):766-71. doi: 10.1097/SLA.0b013e3181bd920a. — View Citation

Zalinski S, Soubrane O, Scatton O. Reducing biliary morbidity in full graft deceased donor liver transplantation: is it really a matter of T-tube? Ann Surg. 2010 Sep;252(3):570-1; author reply 571-2. doi: 10.1097/SLA.0b013e3181f07a6b. — View Citation

* Note: There are 28 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of biliary strictures and biliary fistulae within six months post-transplantation.	A biliary leakage is defined by the presence of bile in the abdominal drainage, and/or an intra-abdominal collection with bilious content requiring drainage.; A biliary stenosis is defined by a size discrepancy between the two sides of the bile duct anastomosis on specific imaging (MR cholangiography, ERCP), associated to an upstream bile tract distention, with a clinical and biological cholestasis, after excluding other cholestasis causes (rejection, viral reactivation).	6 months
Secondary	Incidence of specific complications related to the IST and its extraction by endoscopy	Secondary endpoints are the incidence of specific complications related to the IST and its extraction by endoscopy: cholangitis, stent migration, extraction difficulties, acute pancreatitis, digestive perforation, hemorrhage.	6 months
Secondary	Graft survival	Incidence of graft loss, i.e. retransplantation rate	6 months
Secondary	Patient survival	Incidence of patient death	6 months