Liver cell injury in acetaminophen overdose.
Conditions
Interventions
A Phase III multi-centre prospective randomized clinical trial with three treatment arms.
The patients in each centre will also be stratified into 4 groups based on reported dose ingested (>10 g) an
Sponsors
South Asian Clinical Toxicology Research Collaboration (SACTRC)
Eligibility
Inclusion criteria
Inclusion criteria: 1. Age 16 years and above 2. All patients who have taken a paracetamol overdose (>200mg/kg) where the physician determines an antidote is to be administered
Exclusion criteria
Exclusion criteria: 1. Patients presenting 24 hours or more after poisoning. 2. Patients who have already received an antidote (possible in other hospitals prior to transfer). 3. Patients who have received charcoal (which would interfere with oral antidotes). 4. Patients under the age of 16. 5. Patients who are institutionalized for any mental health condition. 6. Patients with known cognitive impairment (e.g. dementia). 7. Patients with unrelated life threatening illness (e.g. terminal cancer). 8. Patients who are pregnant. 9. Patients who have had a paracetamol overdose in the previous 4 weeks or have taken a significant dose of any other toxic substance in addition to paracetamol. 10. Patients who are on warfarin.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Proportion of patients with miRNA (micro (Micro Ribonucleic acid) evidence of progressive hepatotoxicity following treatment for paracetamol overdose. This will be defined as a ten-fold or greater rise in miR122 over 24 hours from initial tests. [miR122 (micro RNA miR122): On admission (t=0) otherwise t=-5(just before starting the treatment) if there is delay >2hrs to initiate the antidote, and at the 24 hours (end of the treatment).] | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. ALT > 50% elevated over pre-treatment value (ALT- alanine transaminase levels) 2. ALT above 1000 IU/L at any time point 3. INR > 2 at any time point (INR- international normalized ratio) 4. APAP-adduct concentrations Length of hospital stay (APAP-acetyl-para-aminophenol) 5. Number of days spent in the Intensive Care Unit. 6. Adverse antidote effects including nausea, vomiting, rash, hypotension, bronchospasm. 7. Proportion with full adherence to standard regimen in each arm 8. Log change in other miRNA (Micro Ribonucleic acid) 9. Acute kidney injury 10. Severe acute liver injury 11. Death [1. ALT: on admission (t=0) and at t8, t16, t24, and t36 hours post ingestion, and thereafter daily (Dn) until discharge 2. INR: t=0 and at 8, 16, 24, and 36 hours post ingestion, and thereafter daily until discharge. 3. APAP adduct concentrations: t=0 otherwise t=-5 (just before starting the treatment if there is delay >2hrs to initiate the antidote) and at the 24 hours (end of the treatment). 4. Length of Hospital Stay. 5. Adverse antidote effects including nausea, vomiting,rash,hypotension,bronchospasm; t=0 and at 8, 16, 24 hrs 6. Proportion with full adherence to standard regimen in each arm at 24 hours. 7. Log change in other micro ribonucleic acids (miRNAs):On admission t=0 otherwise t=-5 (just before starting the antidote if there is delay >2hrs to initiate the antidote) and at the 24 hours (end of the treatment) 8. Acute kidney injury: on admission and at 8, 16, 24, and 36 hours post ingestion, and thereafter daily until discharge. 9. Severe acute liver injury: t=0 and at 8, 16, 24, and 36 hours post ingestion, ] | — |
Countries
Sri Lanka
Contacts
Public ContactProf.Indika Bandara Gawarammana
Professor in Medicine
Outcome results
None listed