Trial reportEBioMedicine2019
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).
Trial report in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 26 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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)
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
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- N-Acetylcysteine for Preventing Acetaminophen-Induced Liver Injury: A Comprehensive Review.Frontiers in pharmacology · 2022Pooled it
- Prediction of Acute Liver Injury Trajectory in Patients Following Acetaminophen Overdose: A Multibiomarker Machine Learning Proof-of-Concept Study.Clinical pharmacology and therapeutics · 2026Article
- Potential Therapeutic Strategies for Steatosis, Oxidative Stress, Inflammation, and Fibrosis in Liver Disease.International journal of molecular sciences · 2026Review
- A point-of-care diagnostic for drug-induced liver injury using surface-enhanced Raman scattering lateral flow immunoassay.Nature communications · 2025Article
- The emerging role of alternatively activated macrophages to treat acute liver injury.Archives of toxicology · 2025Review
- Clinically relevant therapeutic approaches against acetaminophen hepatotoxicity and acute liver failure.Biochemical pharmacology · 2024Review
- Targeting chronic liver diseases: Molecular markers, drug delivery strategies and future perspectives.International journal of pharmaceutics · 2024Review
- Article
- Loss of microRNA-21 protects against acetaminophen-induced hepatotoxicity in mice.Archives of toxicology · 2023Article
- Exacerbated Neuropathy in POLAR A and M Trials Due to Redox Interaction of PledOx-Associated MnAntioxidants (Basel, Switzerland) · 2023Article
- Fructose as a novel nutraceutical for acetaminophen (APAP)-induced hepatotoxicity.Metabolism and target organ damage · 2023Article
- Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage.Nature communications · 2022Article
- Oxidant Stress and Acetaminophen Hepatotoxicity: Mechanism-Based Drug Development.Antioxidants & redox signaling · 2021Article
- Novel Therapies for the Treatment of Drug-Induced Liver Injury: A Systematic Review.Frontiers in pharmacology · 2021Review
- Drug-Induced Liver Injury: Clinical Evidence of N-Acetyl Cysteine Protective Effects.Oxidative medicine and cellular longevity · 2021Review
- Novel strategies for the treatment of acetaminophen hepatotoxicity.Expert opinion on drug metabolism & toxicology · 2020Review
- The development and hepatotoxicity of acetaminophen: reviewing over a century of progress.Drug metabolism reviews · 2020Review
- May Mangafodipir or Other SOD Mimetics Contribute to Better Care in COVID-19 Patients?Antioxidants (Basel, Switzerland) · 2020Article
- Chemotherapy-induced peripheral neuropathy-part 2: focus on the prevention of oxaliplatin-induced neurotoxicity.Pharmacological reports : PR · 2020Review
- Novel Therapeutic Approaches Against Acetaminophen-induced Liver Injury and Acute Liver Failure.Toxicological sciences : an official journal of the Society of Toxicology · 2020Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundThe POP Trial was a phase 1, open-label, rising-dose, randomised study that explored the safety and tolerability of calmangafodipir (superoxide dismutase mimetic) co-treatment with n-acetylcysteine (NAC) for paracetamol overdose.
methodsPatients were recruited at the Royal Infirmary of Edinburgh (8th June 2017-10th May 2018). Inclusion criterion: adults within 24 h of a paracetamol overdose that required NAC. Within each of 3 sequential cohorts, participants were randomly assigned, with concealed allocation, to NAC and a single intravenous calmangafodipir dose (n = 6) or NAC alone (n = 2). Calmangafodipir doses were 2, 5, or 10 μmol/kg. Participants, study and clinical teams were not blinded. The primary outcome was safety and tolerability. Secondary outcomes were alanine transaminase (ALT), international normalised ratio (INR), keratin-18, caspase-cleaved keratin-18 (ccK18), microRNA-122, and glutamate dehydrogenase (GLDH). (Clinicaltrials.gov:NCT03177395).
findingsAll 24 participants received their allocated drug doses and were analysed. Primary endpoints: all participants experienced ≥1 adverse event (AE), most commonly gastrointestinal. Patients experiencing ≥1 serious adverse event (SAE): NAC alone, 2/6; NAC + calmangafodipir (2 μmol/kg), 4/6; NAC + calmangafodipir (5 μmol/kg), 2/6; NAC + calmangafodipir (10 μmol/kg), 3/6. No AEs or SAEs were probably or definitely calmangafodipir-related. Secondary safety outcomes demonstrated no differences between groups. With NAC alone, 2/6 had ALT > 100 U/L; with NAC + calmangafodipir, 0/18. No INR difference. Keratin-18 and ccK18 increased in the NAC alone group more than with calmangafodipir (baseline to 20 h fold change, NAC + calmangafodipir (5 μmol/kg) compared to NAC alone: 0.48 (95%CI 0.28-0.83)). microRNA-122 changes were similar to K18, GLDH was frequently undetected.
interpretationCalmangafodipir was tolerated when combined with NAC and may reduce biomarkers of paracetamol toxicity.
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What OpenQuestion holds
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.