Hepatotoxicity, Idiosyncratic Drug Effect, Prednisone
Conditions
Keywords
Prednisone, Idiosyncrasic hepatotoxicity
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.
Interventions
DRUGPrednisone
Placebo
Sponsors
Fundación Pública Andaluza para la Investigación de Málaga en Biomedicina y Salud
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Prednisone medication and its placebo will be identical in appearance and in organoleptic properties.
Intervention model description
Controlled with placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Contacts
Primary ContactMª Isabel Lucena, PhD
Backup ContactGloria Luque
Outcome results
None listed