Secretin in Ex-situ Liver Perfusion

NCT07651748 | Enrolling By Invitation Phase 1 FDA Drug

• 1 other identifier: MEC-2024-0678
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The main objective is to assess whether the use of human synthetic secretin in a clinical (COR-)NMP procedure can restore physiological HCO3- content of the bile during ex-situ NMP.

Conditions

Liver Transplantation

Outcome Measures

Primary Outcomes (1)

• Cholangiocellular viability assessment - Biliary Bicarbonate

  A comparison will be made between livers that pass cholangiocyte viability assessment and livers that do not pass cholangiocyte viability assessment in the secretin cohort of this study. Analysis will be performed on bile composition, with the main outcome being the response in biliary bicarbonate increase 30 minutes after the second dose of administration (directly after viability assessment with the go-no go for transplantation).

  Periprocedural

Secondary Outcomes (1)

• Cholangiocellular viability assessment - Bile production

  Periprocedural

Other Outcomes (1)

• Comparison with historical cohort - Biliary complications

  Until 6 months post-transplant

Study Arms (2)

Historical control group

NO INTERVENTION

Historical cases of sequential hypo- to normothermic machine perfusion, linked with controlled oxygenated rewarming for 60 minutes (DHOPE-COR-NMP) livers that did not receive synthetic human secretin during the perfusion.

Secretin administration during liver machine perfusion (COR-NMP)

EXPERIMENTAL

These livers will be treated during ex-situ machine perfusion with a blood-based perfusate with doses of human synthetic secretin.

Drug: Secretin administration during ex-situ liver machine perfusion

Interventions

Secretin administration during ex-situ liver machine perfusion DRUG

In at least 20 cases of sequential hypo- to normothermic machine perfusion, linked with controlled oxygenated rewarming (COR) for 60 minutes (DHOPE-COR-NMP) livers, the investigators will add 16mcg of synthetic human secretin to the perfusate at the start of COR phase of the protocol and a second dose of 16mcg during the NMP phase after the decision moment whether to transplant or not. This number was chosen based on an average acceptance rate of 70%, and therefore would generate 14 transplanted livers while 6 livers are expected not to be transplanted (not passing the standard viability criteria). As the acceptance rate is subject to fluctuations over time (due to variations in the quality of donor offers), the investigators want to include at least 14 transplanted livers and 6 livers that are not transplanted (not passing the standard viability criteria), in order to have the best representative situation. When both numbers are reached, inclusions will stop.

Secretin administration during liver machine perfusion (COR-NMP)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients (\>18 years old)
• Donor livers that required resuscitation and viability assessment through the previously published sequential hypo- and normothermic liver machine perfusion (DHOPE-COR-NMP) protocol based on a blood-based perfusate.

You may not qualify if:

• Multiorgan transplantation
• Split liver transplant
• Living donor liver transplantation
• Organ donation after Euthanasia
• Previous donor organ perfusion (e.g. Normothermic Regional Perfusion)

Sponsors & Collaborators

• Erasmus Medical Center: lead

Study Sites (1)

Erasmus Medical Center

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Related Publications (8)

• de Jong IEM, Bodewes SB, van Leeuwen OB, Oosterhuis D, Lantinga VA, Thorne AM, Lascaris B, van den Heuvel MC, Wells RG, Olinga P, de Meijer VE, Porte RJ. Restoration of Bile Duct Injury of Donor Livers During Ex Situ Normothermic Machine Perfusion. Transplantation. 2023 Jun 1;107(6):e161-e172. doi: 10.1097/TP.0000000000004531. Epub 2023 May 23.

  PMID: 36721302 BACKGROUND

• Dutch Transplant Registry, Numbers about organ transplantation 2021-2022

  BACKGROUND

• Eden J, Sousa Da Silva R, Cortes-Cerisuelo M, Croome K, De Carlis R, Hessheimer AJ, Muller X, de Goeij F, Banz V, Magini G, Compagnon P, Elmer A, Lauterio A, Panconesi R, Widmer J, Dondossola D, Muiesan P, Monbaliu D, de Rosner van Rosmalen M, Detry O, Fondevila C, Jochmans I, Pirenne J, Immer F, Oniscu GC, de Jonge J, Lesurtel M, De Carlis LG, Taner CB, Heaton N, Schlegel A, Dutkowski P. Utilization of livers donated after circulatory death for transplantation - An international comparison. J Hepatol. 2023 May;78(5):1007-1016. doi: 10.1016/j.jhep.2023.01.025. Epub 2023 Feb 4.

  PMID: 36740047 BACKGROUND

• Orman ES, Mayorga ME, Wheeler SB, Townsley RM, Toro-Diaz HH, Hayashi PH, Barritt AS 4th. Declining liver graft quality threatens the future of liver transplantation in the United States. Liver Transpl. 2015 Aug;21(8):1040-50. doi: 10.1002/lt.24160.

  PMID: 25939487 BACKGROUND

• Nemes B, Gaman G, Polak WG, Gelley F, Hara T, Ono S, Baimakhanov Z, Piros L, Eguchi S. Extended-criteria donors in liver transplantation Part II: reviewing the impact of extended-criteria donors on the complications and outcomes of liver transplantation. Expert Rev Gastroenterol Hepatol. 2016 Jul;10(7):841-59. doi: 10.1586/17474124.2016.1149062. Epub 2016 Mar 2.

  PMID: 26831547 BACKGROUND

• van Leeuwen OB, Bodewes SB, Lantinga VA, Haring MPD, Thorne AM, Bruggenwirth IMA, van den Berg AP, de Boer MT, de Jong IEM, de Kleine RHJ, Lascaris B, Nijsten MWN, Reyntjens KMEM, de Meijer VE, Porte RJ. Sequential hypothermic and normothermic machine perfusion enables safe transplantation of high-risk donor livers. Am J Transplant. 2022 Jun;22(6):1658-1670. doi: 10.1111/ajt.17022. Epub 2022 Apr 18.

  PMID: 35286759 BACKGROUND

• Tabibian JH, Masyuk AI, Masyuk TV, O'Hara SP, LaRusso NF. Physiology of cholangiocytes. Compr Physiol. 2013 Jan;3(1):541-65. doi: 10.1002/cphy.c120019.

  PMID: 23720296 BACKGROUND

• Hohenester S, Wenniger LM, Paulusma CC, van Vliet SJ, Jefferson DM, Elferink RP, Beuers U. A biliary HCO3- umbrella constitutes a protective mechanism against bile acid-induced injury in human cholangiocytes. Hepatology. 2012 Jan;55(1):173-83. doi: 10.1002/hep.24691.

  PMID: 21932391 BACKGROUND

Study Officials

• Robert J Porte, MD, PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of HPB- and Transplant Surgery

Model Details: One study group receives secretin therapy, whilst the other group consists of historical controls without secretin therapy

Study Record Dates

• First Submitted: January 26, 2026
• First Posted: June 16, 2026
• Study Start: April 26, 2025
• Primary Completion: June 1, 2026
• Study Completion (Estimated): October 1, 2026
• Last Updated: June 16, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)