Clinical trial NCT06251232: Proof-of-concept to Evaluate the Efficacy and Safety of Prednisone in Idiosyncratic Hepatotoxicity
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Hepatotoxicity
Idiosyncratic Drug Effect
Prednisone
Keywords: Prednisone
Idiosyncrasic hepatotoxicity
Lead sponsor: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
Sponsor class: OTHER
First posted: 2024-02-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Controlled with placebo
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Total bilirubin
timeFrame: Through study completation, an average 2 years
Secondary outcomes:
measure: Peak alanine aminotransferase level
timeFrame: 2 years
measure: Aspartate aminotransferase level
timeFrame: 2 years
measure: International normalized ratio values
timeFrame: Through study completation, an average 2 years
Other outcomes:
Locations:
Study officials:
affiliation: SAS
name: Raúl Andrade, PhD
role: PRINCIPAL_INVESTIGATOR
References: