Proof-of-concept to Evaluate the Efficacy and Safety of Prednisone in Idiosyncratic Hepatotoxicity (DILICORT)

Proof-of-concept Phase II Study to Evaluate the Efficacy and Safety of Prednisone in the Treatment of Idiosyncratic Hepatotoxicity and Its Mechanistic Pathways Through an Integrative Analysis: the DILI-CORT Clinical Trial

This trial´s aim is to assess if oral prednisone (compared to placebo), administered over five weeks is beneficial in terms of decreased total bilirubin (TBL): reduction of the peak of TBL at least 50% at 14 days or reduction in the time to normalisation of TBL value.

Study Overview

• Status: Not yet recruiting
• Conditions: Prednisone; Hepatotoxicity; Idiosyncratic Drug Effect
• Intervention / Treatment: Drug: Prednisone

Detailed Description

This trial´s aim is to assess if oral prednisone (compared to placebo), administered over five weeks is beneficial in terms of decreased total bilirubin (TBL): reduction of the peak of TBL at least 50% at 14 days or reduction in the time to normalisation of TBL value, and to assess if oral prednisone (compared to placebo) is safe and well tolerated in patients with acute moderate to severe DILI.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Mª Isabel Lucena, PhD; Phone Number: 34952131572; Email: lucena@uma.es
• Study Contact Backup: Name: Gloria Luque; Phone Number: 34951291977; Email: gloria.luque@ibima.eu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Female and male patients, aged ≥ 18 years.
2. Patients who have been diagnosed with DILI by the expert committee.
3. Patients with moderate to severe DILI (elevations of ALT or AST ≥ 5 times the Upper Limit of Normal (ULN) and serum TBL ≥ 2.5 mg/dL).
4. Patients who do not show a 15% reduction in ALT values or TBL continues to increase 5-10 days after liver damage recognition despite the withdrawal of the culprit drug.

Exclusion Criteria:

1. No clear DILI diagnosis after an expert committee DILI assessment.
2. DILI due to immune-checkpoint inhibitors.
3. Presence of active infection as evidenced by positive urine or blood culture.
4. Acute liver failure (international normalized ratio (INR) > 1.5 and hepatic encephalopathy).
5. Model for End-Stage Liver Disease (MELD) ≥ 30.
6. Known hypersensitivity to prednisone or placebo components.
7. Pregnant or nursing mothers.
8. Co-existing infection with hepatitis C, hepatitis B, or human immunodeficiency virus (HIV).
9. Patients already receiving systemic steroids or other immunosuppressants.
10. Inability to provide informed consent.
11. Presence of clinically significant comorbid illnesses (by clinician's criteria) that might impede the completion of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo treatment; Placebo	Drug: Prednisone; Placebo; Other Names: Comparator
Active Comparator: Active treatment; Oral prednisone	Drug: Prednisone; Placebo; Other Names: Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total bilirubin	To assess if oral prednisone (compared to placebo), administered over five weeks is beneficial in terms of decreased total bilirubin (TBL): reduction of the peak of TBL at least 50% at 14 days or reduction in the time to normalisation of TBL value.	Through study completation, an average 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak alanine aminotransferase level	Comparison prednisone/placebo when reducing peak alanine aminotransferase (ALT), aspartate aminotransferase (AST) and international normalized ratio (INR) values by at least 50% at day 7 or reducing the time to normalisation.	2 years
Aspartate aminotransferase level	Comparison prednisone/placebo when reducing peak alanine aminotransferase (ALT), aspartate aminotransferase (AST) and international normalized ratio (INR) values by at least 50% at day 7 or reducing the time to normalisation.	2 years
International normalized ratio values	Comparison prednisone/placebo when reducing peak alanine aminotransferase (ALT), aspartate aminotransferase (AST) and international normalized ratio (INR) values by at least 50% at day 7 or reducing the time to normalisation.	Through study completation, an average 2 years

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
• Investigators: Principal Investigator: Raúl Andrade, PhD, SAS

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: December 12, 2023
• First Submitted That Met QC Criteria: February 1, 2024
• First Posted (Actual): February 9, 2024

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Prednisone; Idiosyncrasic hepatotoxicity
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: DILICORT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: National and international webs, manuscript
• IPD Sharing Time Frame: After 3 years
• IPD Sharing Access Criteria: Open access
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR

Drug and device information, study documents

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