Trial reportPloS one2017
Phase I randomized clinical trial of N-acetylcysteine in combination with an adjuvant probenecid for treatment of severe traumatic brain injury in children.
Trial report in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01322009 (Overcoming Membrane Transporters to Improve CNS Drug Delivery), which is not on this map. Cited by 39 papers, 3 of them syntheses that pooled 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.
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.
Overcoming Membrane Transporters to Improve CNS Drug Delivery
Who cites it
39 citing papers in PubMed, 3 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- N-Acetylcysteine in Neurological Disorders: A Systematic Review of Clinical and Translational Evidence Across Seven Disorders.International journal of molecular sciences · 2026Pooled it
- Inorganic, Synthetic, Natural, and Innovative Hybrid Hydrogen Sulfide Donors and Inhibitors of Its Biosynthesis in the Treatment of Central and Peripheral Nervous System Injuries: A Systematic Analytical Review.International journal of molecular sciences · 2025Pooled it
- Effects of early adjunctive pharmacotherapy on serum levels of brain injury biomarkers in patients with traumatic brain injury: a systematic review of randomized controlled studies.Frontiers in pharmacology · 2023Pooled it
- Repurposing of high-dose N-acetylcysteine as anti-inflammatory, antioxidant and neuroprotective agent in moderate to severe traumatic brain injury patients: a randomized controlled trial.Inflammopharmacology · 2025Trial
- Exploratory Application of Neuropharmacometabolomics in Severe Childhood Traumatic Brain Injury.Critical care medicine · 2018Trial
- Review
- Redefining the role of the thiol-based agentRSC medicinal chemistry · 2026Review
- New Approaches and Strategies for the Repurposing of Iron Chelating/Antioxidant Drugs for Diseases of Free Radical Pathology in Medicine.Antioxidants (Basel, Switzerland) · 2025Review
- Brain injury biomarkers as targets for drugs development and personalized treatment for traumatic brain injury patients.Frontiers in pharmacology · 2025Review
- A novel multimodal pharmacologic approach using guanfacine, N-acetylcysteine, and donepezil in severe TBI: a case series.Frontiers in rehabilitation sciences · 2025Article
- Mitochondrial-targeted therapies in traumatic brain injury: From bench to bedside.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Mitochondria-Targeted Antioxidant Therapeutics for Traumatic Brain Injury.Antioxidants (Basel, Switzerland) · 2024Review
- Neuroprotection strategies in traumatic brain injury: Studying the effectiveness of different clinical approaches.Surgical neurology international · 2024Review
- N-Acetylcysteine and Probenecid Adjuvant Therapy for Traumatic Brain Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Multi-Mechanistic Approaches to the Treatment of Traumatic Brain Injury: A Review.Journal of clinical medicine · 2023Review
- Rescuing mitochondria in traumatic brain injury and intracerebral hemorrhages - A potential therapeutic approach.Neurochemistry international · 2021Review
- Targeting Oxidative Stress with Antioxidant Duotherapy after Experimental Traumatic Brain Injury.International journal of molecular sciences · 2021Article
- Recent trends in artificial intelligence-driven identification and development of anti-neurodegenerative therapeutic agents.Molecular diversity · 2021Article
- Impact of pediatric traumatic brain injury on hippocampal neurogenesis.Neural regeneration research · 2021Review
- NAC and Vitamin D Restore CNS Glutathione in Endotoxin-Sensitized Neonatal Hypoxic-Ischemic Rats.Antioxidants (Basel, Switzerland) · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThere are no therapies shown to improve outcome after severe traumatic brain injury (TBI) in humans, a leading cause of morbidity and mortality. We sought to verify brain exposure of the systemically administered antioxidant N-acetylcysteine (NAC) and the synergistic adjuvant probenecid, and identify adverse effects of this drug combination after severe TBI in children.
methodsIRB-approved, randomized, double-blind, placebo controlled Phase I study in children 2 to 18 years-of-age admitted to a Pediatric Intensive Care Unit after severe TBI (Glasgow Coma Scale [GCS] score ≤8) requiring an externalized ventricular drain for measurement of intracranial pressure (ICP). Patients were recruited from November 2011-August 2013. Fourteen patients (n = 7/group) were randomly assigned after obtaining informed consent to receive probenecid (25 mg/kg load, then 10 mg/kg/dose q6h×11 doses) and NAC (140 mg/kg load, then 70 mg/kg/dose q4h×17 doses), or placebos via naso/orogastric tube. Serum and CSF samples were drawn pre-bolus and 1-96 h after randomization and drug concentrations were measured via UPLC-MS/MS. Glasgow Outcome Scale (GOS) score was assessed at 3 months.
resultsThere were no adverse events attributable to drug treatment. One patient in the placebo group was withdrawn due to adverse effects. In the treatment group, NAC concentrations ranged from 16,977.3±2,212.3 to 16,786.1±3,285.3 in serum and from 269.3±113.0 to 467.9±262.7 ng/mL in CSF, at 24 to 72 h post-bolus, respectively; and probenecid concentrations ranged from 75.4.3±10.0 to 52.9±25.8 in serum and 5.4±1.0 to 4.6±2.1 μg/mL in CSF, at 24 to 72 h post-bolus, respectively (mean±SEM). Temperature, mean arterial pressure, ICP, use of ICP-directed therapies, surveillance serum brain injury biomarkers, and GOS at 3 months were not different between groups.
conclusionsTreatment resulted in detectable concentrations of NAC and probenecid in CSF and was not associated with undesirable effects after TBI in children.
trial registrationClinicalTrials.gov NCT01322009.
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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.