Clinical trial NCT03497104: The Markers and Paracetamol Poisoning Study 2
Official title: The Markers and Paracetamol Poisoning Study 2 - Early Diagnosis of Drug-induced Liver Injury Using Point of Care Detection of microRNA
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Paracetamol Overdose
Lead sponsor: NHS Lothian
Sponsor class: OTHER_GOV
First posted: 2018-04-13
Enrollment: 464
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients presenting to Emergency Department or Acute Medical Unit with paracetamol overdose

Brief summary: Paracetamol overdose is one of the most common medical emergencies. Annually in the UK, 100,000 people seek medical attention and 50,000 need hospital admission. Treatment is with the antidote acetylcysteine (NAC), which is effective but takes 21 hours to administer intravenously and frequently produces adverse reactions.

Current tools that are used to decide who needs treatment are inadequate. this trial team have identified and validated new blood tests that accurately identify those patients at risk of liver injury by quantifying the fundamental in vivo toxicity mechanisms.

This study aim to gain further samples in order to develop a new point-of-care test specifically for the detection of liver damage.

Detailed description: Paracetamol overdose is one of the most common medical emergencies. Annually in the UK, 100,000 people seek medical attention and 50,000 need hospital admission. Treatment is with the antidote acetylcysteine (NAC), which is effective but takes 21 hours to administer intravenously and frequently produces adverse reactions. Paracetamol is the commonest cause of acute liver failure and directly kills around 200 people/year in the UK. Management of paracetamol overdose is estimated to cost around £48 million/year to the NHS.

Current tools that are used to decide who needs treatment are inadequate. This trial team have identified and validated new blood tests that accurately identify those patients at risk of liver injury by quantifying the fundamental in vivo toxicity mechanisms. Over the last 4 years the team have published data in leading journals such as The Lancet, Lancet Gastroenterology (the MAPP Trial), Hepatology and Clinical Pharmacology \& Therapeutics. The current gold standard marker, serum Alanine Aminotransferase Test (ALT) activity, lacks both sensitivity and specificity for early liver injury. This has resulted in being able to qualify 3 new liver biomarkers in over 1,200 patients (microRNA-122 (miR-122), High Mobility Group Box protein 1 (HMGB1) and keratin-18 (K18)) and demonstrated they predict liver injury at first presentation to hospital with high accuracy at a time when ALT is still normal.

This project develops a new point-of-care (POC) test for circulating microRNA specifically for the detection of liver damage after paracetamol overdose. The team have developed the microRNA biomarker (miR-122) to the point where it has received formal regulatory support from the USA Food and Drug Administration (FDA) and the European Medicines Agency (EMA). The proposed assay has backing from worldwide clinical opinion leaders and pharma partners such as AstraZeneca, GSK and Novartis. The engineering solution for POC microRNA detection is underpinned by robust pilot data and field-leading expertise. The current assay for miR-122 is PCR following extensive sample preparation which is too slow for acute clinical decision making and for dose-escalation decisions. To address this key roadblock (as identified by the FDA) the team will use electrochemical impedance spectroscopy (EIS). the trial team have over 10 years of experience in EIS-based POC test development. Pilot data demonstrate that EIS can detect miR-122 spiked into buffer and distinguish patients with DILI (high miR-122) from healthy subjects (low miR-122).

Eligibility criteria: Inclusion Criteria:

1. Age 16 years and over.
2. Hospital attendance with paracetamol overdose alone or as part of a mixed overdose
3. Patient is able to give informed consent

Exclusion Criteria:

1. Patient detained under the Mental Health Act
2. Inability to provide informed consent
3. Unreliable history of overdose
4. Prisoners

Primary outcomes:
measure: To establish a biobank of human serum samples from patients with paracetamol overdose to develop and test the performance of our POC Test
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
facility: NHS Lothian
Study officials:
affiliation: University of Edinburgh
name: James Dear
role: PRINCIPAL_INVESTIGATOR
References: