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

Phase 2

Not yet recruiting

• Conditions: Hepatotoxicity; Prednisone; Idiosyncratic Drug Effect
• Interventions: Drug: Prednisone

• Registration Number: NCT06251232
• Lead Sponsor: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud

Brief Summary

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.

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 Timeline

• Status Verified: 2023-11
• Study First Submitted: 2023-12-12
• Study First Submitted QC: 2024-02-01
• Study First Posted: 2024-02-09
• Last Update Submitted: 2024-04-04
• Last Update Posted: 2024-04-05
• Study Start: 2024-05-01
• Primary Completion: 2027-12-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 60

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active treatment	Prednisone	Oral prednisone
Placebo treatment	Prednisone	Placebo

Primary Outcome Measures

Name	Time	Method
Total bilirubin	Through study completation, an average 2 years	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.

Secondary Outcome Measures

Name	Time	Method
Aspartate aminotransferase level	2 years	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.
International normalized ratio values	Through study completation, an average 2 years	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.
Peak alanine aminotransferase level	2 years	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.