Trial reportAnnals of neurology2021
A Pilot Randomized, Controlled, Double-Blind Trial of Bumetanide to Treat Neonatal Seizures.
Trial report in Annals of neurology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 8 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
50 citing papers in PubMed, 8 syntheses or guidelines pooled it, 94 citations in OpenAlex.
- Pooled it
- [Guideline for the diagnosis and treatment of common neonatal diseases in primary healthcare institutions: neonatal seizures (2025)].Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics · 2025Guideline
- Prevalence of hearing impairment in neonatal encephalopathy due to hypoxia-ischemia: a systematic review and meta-analysis.Pediatric research · 2025Pooled it
- Eligible Infants Included in Neonatal Clinical Trials and Reasons for Noninclusion: A Systematic Review.JAMA network open · 2024Pooled it
- Race and Ethnicity of Infants Enrolled in Neonatal Clinical Trials: A Systematic Review.JAMA network open · 2023Pooled it
- Anti-seizure medications for neonates with seizures.The Cochrane database of systematic reviews · 2023Pooled it
- Efficacy of the anti-seizure medications in acute symptomatic neonatal seizures caused by stroke. A systematic review.Acta bio-medica : Atenei Parmensis · 2022Pooled it
- Efficacy and Safety of Levetiracetam vs. Phenobarbital for Neonatal Seizures: A Systematic Review and Meta-Analysis.Frontiers in neurology · 2021Pooled it
- Trial
- Comparison of the effect of phenobarbital & levetiracetam in the treatment of neonatal abstinence syndrome (NAS) as adjuvant treatment in neonates admitted to the neonatal intensive care unit: a randomized clinical trial.BMC pregnancy and childbirth · 2024Trial
- Risk of seizures in neonates with hypoxic-ischemic encephalopathy receiving hypothermia plus erythropoietin or placebo.Pediatric research · 2023Trial
- Clarifications regarding bumetanide for neonatal seizures.Epilepsia · 2022Trial
- Advancing the Paradigm of Temporal Lobe Epilepsy as a Network Disease: The Promise of Biomarkers and Targeted Disease Modification.International journal of molecular sciences · 2026Review
- WNK-SPAK/OSR1 signaling pathway facilitates ictal activity via reduced neuronal chloride extrusion rate.bioRxiv : the preprint server for biology · 2026Article
- GABACellular and molecular neurobiology · 2026Review
- Enhancing KCC2 function reduces interictal activity and prevents seizures in temporal lobe epilepsy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Retrospective, Multicenter Study of Lacosamide to Treat Neonatal Seizures.Annals of the Child Neurology Society · 2026Article
- Temporal and cell-type specific SPAK-NKCC1 disruption following severe TBI in the developing gyrencephalic brain.Acta neuropathologica communications · 2026Article
- Updated recommendations for the design of therapeutic trials for neonatal seizures.Pediatric research · 2026Review
- Synthesis of new sulfoximines and sulfonimidamides derivatives as NKCC1 inhibitors.Frontiers in chemistry · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveIn the absence of controlled trials, treatment of neonatal seizures has changed minimally despite poor drug efficacy. We tested bumetanide added to phenobarbital to treat neonatal seizures in the first trial to include a standard-therapy control group.
methodsA randomized, double-blind, dose-escalation design was employed. Neonates with postmenstrual age 33 to 44 weeks at risk of or with seizures were eligible. Subjects with electroencephalography (EEG)-confirmed seizures after ≥20 and <40mg/kg phenobarbital were randomized to receive additional phenobarbital with either placebo (control) or 0.1, 0.2, or 0.3mg/kg bumetanide (treatment). Continuous EEG monitoring data from ≥2 hours before to ≥48 hours after study drug administration (SDA) were analyzed for seizures.
resultsSubjects were randomized to treatment (n = 27) and control (n = 16) groups. Pharmacokinetics were highly variable among subjects and altered by hypothermia. The only statistically significant adverse event was diuresis in treated subjects (48% vs 13%, p = 0.02). One treated (4%) and 3 control subjects died (19%, p = 0.14). Among survivors, 2 of 26 treated subjects (8%) and 0 of 13 control subjects had hearing impairment, as did 1 nonrandomized subject. Total seizure burden varied widely, with much higher seizure burden in treatment versus control groups (median = 3.1 vs 1.2 min/h, p = 0.006). There was significantly greater reduction in seizure burden 0 to 4 hours and 2 to 4 hours post-SDA (both p < 0.01) compared with 2-hour baseline in treatment versus control groups with adjustment for seizure burden.
interpretationAlthough definitive proof of efficacy awaits an appropriately powered phase 3 trial, this randomized, controlled, multicenter trial demonstrated an additional reduction in seizure burden attributable to bumetanide over phenobarbital without increased serious adverse effects. Future trials of bumetanide and other drugs should include a control group and balance seizure severity. ANN NEUROL 2021;89:327-340.
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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.