Proof-of-concept phase II study protocol to evaluate the efficacy and safety of prednisone in the treatment of idiosyncratic hepatotoxicity and its mechanistic pathways through an integrative analysis: the DILICORT clinical trial
4 affiliations
- 1IBIMA Plataforma Bionand, Instituto de Investigación Biomédica de Málaga, Servicios de Aparato Digestivo y Farmacología Clínica, Hospital Universitario Virgen de la Victoria, Departamentos de Medicina y Dermatología y de Farmacología y Pediatría, Universidad de Málaga
- 2Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)
- 3Unidad de Investigación Clínica y Ensayos Clínicos, Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina
- 4Plataforma de Investigación Clínica, Spanish Clinical Research Network (SCReN), Instituto de Salud Carlos III
Abstract
Introduction: Idiosyncratic drug-induced liver injury (DILI) is an unpredictable adverse reaction ranging from mild liver enzyme elevations to acute liver failure, with management largely limited to withdrawal of the causative drug. An international propensity score-matched study of 724 DILI cases associated corticosteroid therapy with a higher liver enzyme normalization rate, particularly in moderate-to-severe cases without early improvement. These findings informed the design and selection f endpoints for the DILICORT trial, which aims to evaluate the efficacy and safety of prednisone in patients with DILI. The trial will also investigate the effects of treatment on liver function recovery and identify biomarkers associated with therapeutic response.
Methods: DILICORT (EUCT 2024-513004-33–00; NCT06251232) is a national, randomized, double-blind, placebo-controlled phase II proof-of-concept trial. Sixty patients with moderate-to-severe DILI who show no ≥ 15% reduction in alanine aminotransferase (ALT) or have persistently increasing total bilirubin levels within 5–10 days will be recruited across 15 Spanish centers and followed for 12 weeks. Participants will be randomized to receive a 5-week course of prednisone or matching placebo. The primary objectives are to evaluate prednisone efficacy, assessed by the time to bilirubin reduction or normalization, and its safety and tolerability. Secondary objectives include changes in ALT, aspartate aminotransferase and international normalized ratio, progression to acute liver failure, and health-related quality of life. In addition, there are mechanistic objectives focused on elucidating DILI pathogenesis and biomarker discovery.
Discussion: DILICORT is the first multicenter, randomized, double-blind, placebo-controlled trial of prednisone in acute idiosyncratic DILI, designed to provide the highest evidence for this therapeutic approach. It specifically targets patients with moderate-to-severe DILI who do not show a favorable early clinical course and incorporates centralized adjudication of suspected DILI cases. Its integrated mechanistic approach may improve understanding of DILI pathophysiology, identify prognostic and treatment-response biomarkers, and facilitate the development of precision medicine strategies and evidence-based clinical guidelines.
Clinical Trial Registration: https://www.clinicaltrialsregister.eu/ctr-search/search , identifier EUCT 2024-513004-33-00; https://clinicaltrials.gov/ , identifier NCT06251232.
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BibTeX
@article{garridorodriguez2026proofofconcept,
title = {{Proof-of-concept phase II study protocol to evaluate the efficacy and safety of prednisone in the treatment of idiosyncratic hepatotoxicity and its mechanistic pathways through an integrative analysis: the DILICORT clinical trial}},
author = {Vanesa Garrido-Rodríguez and Ángela Remesal-Doblado and Miren García-Cortés and Hao Niu and Jose Cárdenas-Quesada and José M. Pinazo-Bandera and Juan Pedro Toro-Ortiz and Elena Pérez-López and Rocío Moreno-González and Elvira Bonilla-Toyos and Daniel E. Di Zeo-Sánchez and Gonzalo Matilla-Cabello and Marina Villanueva-Paz and Raúl J. Andrade and M. Isabel Lucena and Ismael Alvarez-Alvarez and Judith Sanabria-Cabrera and Mercedes Robles-Díaz},
journal = {Frontiers in Pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1963613},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1963613/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Proof-of-concept phase II study protocol to evaluate the efficacy and safety of prednisone in the treatment of idiosyncratic hepatotoxicity and its mechanistic pathways through an integrative analysis: the DILICORT clinical trial
AU - Vanesa Garrido-Rodríguez
AU - Ángela Remesal-Doblado
AU - Miren García-Cortés
AU - Hao Niu
AU - Jose Cárdenas-Quesada
AU - José M. Pinazo-Bandera
AU - Juan Pedro Toro-Ortiz
AU - Elena Pérez-López
AU - Rocío Moreno-González
AU - Elvira Bonilla-Toyos
AU - Daniel E. Di Zeo-Sánchez
AU - Gonzalo Matilla-Cabello
AU - Marina Villanueva-Paz
AU - Raúl J. Andrade
AU - M. Isabel Lucena
AU - Ismael Alvarez-Alvarez
AU - Judith Sanabria-Cabrera
AU - Mercedes Robles-Díaz
PY - 2026
DA - 2026/10/26
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1963613
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1963613/full
AB - Introduction: Idiosyncratic drug-induced liver injury (DILI) is an unpredictable adverse reaction ranging from mild liver enzyme elevations to acute liver failure, with management largely limited to withdrawal of the causative drug. An international propensity score-matched study of 724 DILI cases associated corticosteroid therapy with a higher liver enzyme normalization rate, particularly in moderate-to-severe cases without early improvement. These findings informed the design and selection f endpoints for the DILICORT trial, which aims to evaluate the efficacy and safety of prednisone in patients with DILI. The trial will also investigate the effects of treatment on liver function recovery and identify biomarkers associated with therapeutic response. Methods: DILICORT (EUCT 2024-513004-33–00; NCT06251232) is a national, randomized, double-blind, placebo-controlled phase II proof-of-concept trial. Sixty patients with moderate-to-severe DILI who show no ≥ 15% reduction in alanine aminotransferase (ALT) or have persistently increasing total bilirubin levels within 5–10 days will be recruited across 15 Spanish centers and followed for 12 weeks. Participants will be randomized to receive a 5-week course of prednisone or matching placebo. The primary objectives are to evaluate prednisone efficacy, assessed by the time to bilirubin reduction or normalization, and its safety and tolerability. Secondary objectives include changes in ALT, aspartate aminotransferase and international normalized ratio, progression to acute liver failure, and health-related quality of life. In addition, there are mechanistic objectives focused on elucidating DILI pathogenesis and biomarker discovery. Discussion: DILICORT is the first multicenter, randomized, double-blind, placebo-controlled trial of prednisone in acute idiosyncratic DILI, designed to provide the highest evidence for this therapeutic approach. It specifically targets patients with moderate-to-severe DILI who do not show a favorable early clinical course and incorporates centralized adjudication of suspected DILI cases. Its integrated mechanistic approach may improve understanding of DILI pathophysiology, identify prognostic and treatment-response biomarkers, and facilitate the development of precision medicine strategies and evidence-based clinical guidelines. Clinical Trial Registration: https://www.clinicaltrialsregister.eu/ctr-search/search , identifier EUCT 2024-513004-33-00; https://clinicaltrials.gov/ , identifier NCT06251232.
SN - 1663-9812
ER -