Trial reportAnnals of neurology2018
Fingolimod enhances the efficacy of delayed alteplase administration in acute ischemic stroke by promoting anterograde reperfusion and retrograde collateral flow.
Trial report in Annals of neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 2 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
55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 119 citations in OpenAlex.
- Comparing Early National Institutes of Health Stroke Scale Versus 90-Day Modified Rankin Scale Outcomes in Acute Ischemic Stroke Trials: A Systematic Review and Analysis.Journal of the American Heart Association · 2025Pooled it
- The efficacy and safety of fingolimod plus standardized treatment versus standardized treatment alone for acute ischemic stroke: A systematic review and meta-analysis.Pharmacology research & perspectives · 2022Pooled it
- Safety and Efficacy of Otaplimastat in Patients with Acute Ischemic Stroke Requiring tPA (SAFE-TPA): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2 Study.Annals of neurology · 2020Trial
- Beyond Recanalization: Neurovascular Unit Protection and Precision Adjunctive Therapy for Ischemic Stroke in the Reperfusion Era.Biomolecules · 2026Review
- Targeting CD4⁺ T cell infiltration: mechanisms and therapeutic insights into CD4⁺ T cell transmigration across the blood-brain barrier in acute ischemic stroke.Fluids and barriers of the CNS · 2026Review
- Circulating sphingosine-1-phosphate depletion is associated with endothelial activation and altered brain-endothelial S1P pathway expression in ischemic stroke.Fluids and barriers of the CNS · 2026Article
- Neuroinflammation in Ischemic Stroke: Mechanisms, Systemic Interactions, and Therapeutic Targets.Translational stroke research · 2026Review
- The physiological and pathological effects of sphingolipid metabolism and signaling in the central nervous system.Brain pathology (Zurich, Switzerland) · 2026Review
- Back Again to the Future: A New Era for Cerebroprotection.Annals of neurology · 2026Review
- Fingolimod as a Neuroprotective Agent in Ischemic Stroke: A Review of Preclinical and Clinical Evidence.Journal of clinical medicine · 2025Review
- Sphingosine-1-Phosphate Modulation in Neurological Disorders: Insights from MS and Stroke.Brain sciences · 2025Review
- Risk of stroke under disease modifying therapies for multiple sclerosis: a systematic review.Therapeutic advances in neurological disorders · 2025Review
- Arterial specification precedes microvascular restitution in the peri-infarct cortex that is driven by small microvessels.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2025Article
- Sphingosine 1-phosphate receptor 1 modulators exert neuroprotective effects in central nervous system disorders.Frontiers in pharmacology · 2025Review
- Nanotechnology approaches to drug delivery for the treatment of ischemic stroke.Bioactive materials · 2025Review
- CD4Frontiers in immunology · 2025Review
- Multi-Target and Multi-Phase Adjunctive Cerebral Protection for Acute Ischemic Stroke in the Reperfusion Era.Biomolecules · 2024Review
- Molecular Mechanisms of Ischemic Stroke: A Review Integrating Clinical Imaging and Therapeutic Perspectives.Biomedicines · 2024Review
- MARVEL: A Randomized Double-Blind, Placebo-Controlled Trial in Patients Undergoing Endovascular Therapy: Study Rationale and Design.Stroke (Hoboken, N.J.) · 2024Article
- Hemorrhagic Transformation of Ischemic Strokes.International journal of molecular sciences · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 9 institutions in 2 countries.
Funding
Abstract
objectiveThe present study was undertaken to determine the efficacy of coadministration of fingolimod with alteplase in acute ischemic stroke patients in a delayed time window.
methodsThis was a prospective, randomized, open-label, blinded endpoint clinical trial, enrolling patients with internal carotid artery or middle cerebral artery proximal occlusion within 4.5 to 6 hours from symptom onset. Patients were randomly assigned to receive alteplase alone or alteplase with fingolimod. All patients underwent pretreatment and 24-hour noncontrast computed tomography (CT)/perfusion CT/CT angiography. The coprimary endpoints were the decrease of National Institutes of Health Stroke Scale scores over 24 hours and the favorable shift of modified Rankin Scale score (mRS) distribution at day 90. Exploratory outcomes included vessel recanalization, anterograde reperfusion, and retrograde reperfusion of collateral flow.
resultsEach treatment group included 23 patients. Compared with alteplase alone, patients receiving fingolimod plus alteplase exhibited better early clinical improvement at 24 hours and a favorable shift of mRS distribution at day 90. In addition, patients who received fingolimod and alteplase exhibited a greater reduction in the perfusion lesion accompanied by suppressed infarct growth by 24 hours. Fingolimod in conjunction with alteplase significantly improved anterograde reperfusion of downstream territory and prevented the failure of retrograde reperfusion from collateral circulation.
interpretationFingolimod may enhance the efficacy of alteplase administration in the 4.5- to 6-hour time window in patients with a proximal cerebral arterial occlusion and salvageable penumbral tissue by promoting both anterograde reperfusion and retrograde collateral flow. These findings are instructive for the design of future trials of recanalization therapies in extended time windows. Ann Neurol 2018;84:725-736.
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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.