Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03497104 |
| Other study ID # |
244423 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
July 1, 2018 |
| Est. completion date |
May 31, 2023 |
Study information
| Verified date |
September 2022 |
| Source |
NHS Lothian |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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.
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).
