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

Hepatotoxicity Clinical Trial

— DILICORT  

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06251232
• Other study ID #: DILICORT
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: May 1, 2024
• Est. completion date: December 31, 2028

Study information

• Verified date: November 2023
• Source: Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
• Contact: Mª Isabel Lucena, PhD
• Phone: 34952131572
• Email: lucena[@]uma.es
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 31, 2028
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hepatotoxicity

Intervention

Drug:
• Prednisone
Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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