BMJ Open (Feb 2024)

Personalised human albumin in patients with cirrhosis and ascites: design and rationale for the ALB-TRIAL - a randomised clinical biomarker validation trial

  • ,
  • Torben Hansen,
  • Pere Ginès,
  • Wim Laleman,
  • Peer Bork,
  • Vishal C Patel,
  • Debbie Shawcross,
  • Robert Schierwagen,
  • Camila Alvarez-Silva,
  • Florence Servant,
  • Jonel Trebicka,
  • Benjamin Lelouvier,
  • Manimozhiyan Arumugam,
  • Ed J Kuijper,
  • Frank Erhard Uschner,
  • Michael Praktiknjo,
  • Mária Papp,
  • Saeed Shoaie,
  • Michael Kühn,
  • Maja Thiele,
  • Paolo Angeli,
  • Joan Claria,
  • Vicente Arroyo,
  • Manolo Laiola,
  • Benoit Quinquis,
  • Sabine Klein,
  • Minneke J Coenraad,
  • François Fenaille,
  • Debbie Lindsay Shawcross,
  • Wenyi Gu,
  • Adria Juanola,
  • Elisa Pose,
  • Aleksander Krag,
  • Ivica Letunic,
  • Alain Pruvost,
  • Hervé M Blottière,
  • Nathalie Galleron,
  • Cristina López-Vicario,
  • Peter V Treit,
  • Matthias Mann,
  • Jelle Matthijnssens,
  • Mark J W Mcphail,
  • Philipp E Geyer,
  • Hans Olav Melberg,
  • Stefanie Kandels,
  • Cristina Sánchez-Garrido,
  • Florence A Castelli,
  • Christophe Junot,
  • Lars Asphaug,
  • Mads Israelsen,
  • Helene Bæk Juel,
  • Nikolaj Torp,
  • Minneke Coenraad,
  • Marko Korenjak,
  • Ferran Aguilar-Parera,
  • Patricia Sierra-Casas,
  • Anna Bosch-Comas,
  • David Tornai,
  • Boglarka Balogh,
  • Katrine Holtz Thorhauge,
  • Casper Sahl Poulsen,
  • Thea Van Rossum,
  • Suguru Nishijima,
  • Marisa I Keller,
  • Diënty H M Hazenbrink,
  • Sylvain Dechaumet,
  • Sebastian D Burz,
  • Emeline Chu-Van,
  • Etienne Thévenot,
  • Florian A Rosenberger,
  • Sebastian Van Blerk,
  • Amirouche Ouzerdine,
  • Alain Roulet,
  • Jean-Louis-Marie Insonere,
  • Céline Serres,
  • Mathieu Almeida,
  • Florence Thirion,
  • Camille Champion,
  • Chaima Ezzine,
  • Célia Chamignon,
  • Nicolas Lapaque,
  • Mamadou Gabou Thiam,
  • Lore Van Espen,
  • Quinten R Ducarmon,
  • Annelotte GC Broekhoven,
  • Susan Fischer,
  • Romy Zwittink,
  • Itziar De Lecuona,
  • Giulio Rosati,
  • Celia Fuentes-Chust,
  • Arben Merkoçi,
  • Massimo Urban,
  • José Alfonso Marrugo-Ramirez,
  • Ameli Schwalber,
  • Lindsey Ann Edwards,
  • Victoria Tatiana Kronsten,
  • David Moyes,
  • Azadeh Harzandi,
  • Jordi Gratacós-Ginès,
  • Martina Pérez-Guasch,
  • Miriam Pellón,
  • Bryan Contreras,
  • Max Brol,
  • Manfred Fobker,
  • Renata Antonina Feuerborn

DOI
https://doi.org/10.1136/bmjopen-2023-079309
Journal volume & issue
Vol. 14, no. 2

Abstract

Read online

Introduction Human albumin is used in the treatment of complications of cirrhosis. However, the use of long-term human albumin administration is costly and resource demanding for both patients and healthcare systems. A precision medicine approach with biomarkers to predict human albumin treatment response, so-called predictive biomarkers, could make this a viable treatment option in patients with cirrhosis and ascites.Methods and analysis ALB-TRIAL is a multinational, double-blind, placebo-controlled randomised controlled trial. We aim to validate a predictive biomarker, consisting of a panel of circulating metabolites, to predict the treatment response to human albumin in patients with cirrhosis and ascites. All enrolled patients are stratified into a high-expected or low-expected effect stratum of human albumin based on the biomarker outcome. After stratification, patients in each group are randomised into either active treatment (20% human albumin) or corresponding placebo (0.9% NaCl) every 10th day for 6 months. The primary outcome is the cumulative number of liver-related events (composite of decompensation episodes, transjugular intrahepatic shunt insertion, liver transplantation and death). Key secondary outcomes include time-to-event analysis of primary outcome components, an analysis of the total healthcare burden and a health economic analysis.Ethics and dissemination The trial obtained ethical and regulatory approval in Denmark, Germany, the Netherlands, Belgium, Hungary and Spain through the Clinical Trials Information System (CTIS) from 13 February 2023, while UK approvals from the Health Regulatory Authority, Medicines and Healthcare products Regulatory Agency and Research Ethics Committee are pending. Findings will be published in peer-reviewed journals, presented at conferences, communicated to relevant stakeholders and in the public registry of CTIS, following trial completion.Trial registration number NCT05056220 EU CT: 2022-501006-34-01