Evidence map›Paper›PMID 30621764›Full record

ArticleTrials2019

Randomised open label exploratory, safety and tolerability study with calmangafodipir in patients treated with the 12-h regimen of N-acetylcysteine for paracetamol overdose-the PP100-01 for Overdose of Paracetamol (POP) trial: study protocol for a randomised controlled trial.

POP Trial Investigators, James Dear

Registry-linked trialOpen access · goldAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in Trials, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03177395 (A Randomised Open Label Exploratory, Safety and Tolerability Study With PP100-01 in Patients Treated With the 12-hour Regimen of N-Acetylcysteine for Paracetamol/Acetaminophen Overdose), which is not on this map. Cited by 6 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03177395 phase1completednot on this map

A Randomised Open Label Exploratory, Safety and Tolerability Study With PP100-01 in Patients Treated With the 12-hour Regimen of N-Acetylcysteine for Paracetamol/Acetaminophen Overdose (The POP Trial)

TypeinterventionalSponsorEgetis TherapeuticsRan2017 to 2018Enrolled24ConditionsParacetamol OverdoseArmsPP100-01 (calmangafodipir), Acetylcysteine
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Review
  5. Review
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

POP Trial Investigators
James DearThe Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, UK. james.dear@ed.ac.uk.ORCID http://orcid.org/0000-0002-8630-8625
The Queen's Medical Research Institute · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundParacetamol (acetaminophen) overdose (POD) is the commonest cause of acute liver failure in Europe and North America. Current treatment involves the use of the antidote N-acetylcysteine (NAC) in patients deemed at risk of liver damage. This regimen was introduced in the 1970s and has remained largely unchanged even though the initial NAC infusion is frequently associated with adverse reactions, in particular nausea, vomiting, and anaphylactoid reactions. NAC has reduced efficacy for preventing liver injury in those patients who present later after overdose. We designed a randomised study investigating the safety and tolerability of a superoxide dismutase (SOD) mimetic, calmangafodipir (PP100-01), co-treatment with a 12-h NAC regimen compared with NAC treatment alone in patients with POD. METHODS/

designWe have designed an open-label, randomised, exploratory, rising dose design, NAC-controlled, phase 1 safety and tolerability study in patients treated with NAC for POD. A total of 24 patients will be assigned into one of three dosing cohorts of eight patients (n = 6 for PP100-01 and NAC; n = 2 for NAC alone). The doses of PP100-01 are 2, 5, and 10 μmol/kg. The primary outcome is the safety and tolerability of PP100-01 when co-administered with a 12-h NAC regimen compared with NAC treatment alone. Furthermore, the study will explore if PP100-01 has potential efficacy for the treatment of paracetamol-induced liver injury by measurement of conventional clinical and exploratory biomarkers. DISCUSSION: The aim of the study is to test the safety and tolerability of a SOD mimetic, PP100-01, in combination with a 12-h NAC regimen in patients presenting within 24 h of POD. This study will provide valuable data regarding the incidence of adverse events caused by the 12-h NAC plus PP100-01 regimen and may provide evidence of PP100-01 efficacy in the treatment of paracetamol-induced liver injury.

trial registrationEudraCT, 2017-000246-21; ClinicalTrials.gov, NCT03177395 . Registered on 6 June 2017.

Indexed as

AcetaminophenAcetylcysteineChemical and Drug Induced Liver InjuryClinical Trials Data Monitoring CommitteesClinical Trials, Phase I as TopicData Interpretation, StatisticalDrug OverdoseDrug Therapy, CombinationEdetic AcidFemaleHumansMaleOutcome Assessment, Health CarePyridoxal PhosphateRandomized Controlled Trials as TopicResearch DesignAcetaminophenAcetylcysteineEdetic AcidN,N'-bis(pyridoxal-5-phosphate)ethylenediamine-N,N'-diacetic acidPyridoxal PhosphateAcetylcysteineCalmangafodipirHepatotoxicityOverdoseParacetamol

Identifiers

PMID30621764
PMCPMC6325794
OpenAlexW2915018184

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.