Evaluation of Differences Between the Standered NAC Regimen Protocol and the SNAP Regimen Protocol in the Treatment of Paracetamol Toxicity for Cases Presented Early and Late to Assiut University Hospitals in Terms of Safety and Efficiecy.

Official title

Comparative Study of Twelve Hours Versus Twenty One Hours Protocols of Intravenous N-Acetyl Cystiene Treatment in Paracetamol Toxicity at Assiut University Childern's Hospital

Overview

Evaluation of differences between the 21 h NAC regimen protocol and the 12 h NAC regimen protocol in the treatment of paracetamol toxicity (over dose) for cases presented early and late to Assiut University Hospitals in terms of safety and efficiecy.

Detailed description

Acetamenphen is an analgesic and antipyretic drug . It is used as an active ingredient in many over-the-counter and prescription medications. It is generally considered safe at therapeutic doses. However, toxicity can be caused by multiple supratherapeutic doses or an acute, high overdose .

Acetaminophen is metabolized by the cytochrome P450 2E1 to N-acetyl para- benzoquinone-imine (NAPQI), a metabolit extremely toxic to the liver. This process depletes glutathione; thus, NAPQI binds to cellular and mitochondrial proteins to form adducts, impairing mitochondrial respiration and generating oxidative stress .

N-Acetylcysteine (NAC) is a 20-21-hour regimen which involves 3 weight related infusions. The first 150mg/kg is given over 1 hour, second 50mg/kg given over 4 hours and the last 100mg/kg given over 16 hours. This has been the optimal available therapy since 1980 .

Several evidence shows various adverse effect of this regimen which include anaphylactoid reaction, nausea, vomiting and medication error .

Recently the intravenous regimen has been simplified from a three-bag regimen to a two-bag regimen in many parts of the world, which has reduced the early very high concentrations and therefore adverse reaction rate .

Different clinical studies have been carried out to propose the adoption of a shorter regimen, the Scottish and Newcastle Antiemetic Pre-treatment (SNAP) 12-hours NAC regimen into clinical practice .

The SNAP is a two-bag regimen which involves giving 100mg/kg infusion over 2hours, then last 200mg/kg infusion giving over 10hours .

The SNAP regimen confirms that it produces fewer adverse drug reactions (ADRs) and has similar efficacy with regard to preventing liver injury when compared to the 21 h NAC regimen. Further clinical development and adoption of the SNAP regimen could improve treatment safety for this patient group, potentially shorten the length of treatment without compromising antidote effectiveness.

Interventions

• Other Evidence-based medical care for paracetamol toxicity
  adminstration of Standered 21 h NAC regimen for patient comes early within 8 h from ingestion of toxic dose of paracetamol
• Other Evidence-based medical care for paracetamol toxicity
  adminstration of Standered 21 h NAC regimen for patient comes late after 8 h from ingestion of toxic dose of paracetamol
• Other Evidence-based medical care for paracetamol toxicity
  adminstration of 12 h NAC regimen for patient comes early within 8 h from ingestion of toxic dose of paracetamol
• Other Evidence-based medical care for paracetamol toxicity
  adminstration of 12 h NAC regimen for patient comes late after 8 h from ingestion of toxic dose of paracetamol

Primary outcome measures

• 1-Change in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) [Time frame: 1- Day 2]
• change in serum creatinine level [Time frame: Day 2]
• Incidence of adverse drug reactions [Time frame: Day 2]

Secondary outcome measures (2)

• rate of clinical recovery [Time frame: immediately after the intervention]
• incidence of serious complications [Time frame: immediately after the intervention]

Eligibility criteria

Inclusion criteria

• All cases admitted to Assiut University Hospitals with history of acute paracetamol overdose ingestion .

Exclusion criteria

• \* Co-ingestion of other hepatotoxic drugs .

• Pre-existing liver diseases: Chronic hepatitis B or C, Autoimmune hepatitis, Wilson's disease, Known cirrhosis , Sepsis, shock, or hypoxic injury affecting the liver.
• Hemolytic disorders causing abnormal LFTs.
• Genetic or metabolic diseases that affect liver functions.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Egypt · 1 center

• Faculty of Medicine Assiut University — Asyut

Publications

• Morrison EE, Oatey K, Gallagher B, Grahamslaw J, O'Brien R, Black P, Oosthuyzen W, Lee RJ, Weir CJ, Henriksen D, Dear JW; POP Trial Investigators. Principal results of a randomised open label exploratory, safety and tolerability study with calmangafodipir in patients treated with a 12 h regimen of N-acetylcysteine for paracetamol overdose (POP trial). EBioMedicine. 2019 Aug;46:423-430. doi: 10.101 PMID 31311721

Identifiers

NCT: NCT07454590 · TTT of paracetamol toxicity

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗