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Clinical trials landscape

TL;DR — Stroke trials have produced their largest effects by restoring flow: alteplase, thrombectomy, and tissue-selected late-window treatment changed practice, whereas single-target neuroprotection repeatedly failed (NINDS 1995, PMID 7477192; Goyal 2016, PMID 26898852; Nogueira 2018, PMID 29129157). The live registry on 2026-08-30 shows active work on medium/distal occlusions, adjunct antiplatelet or intra-arterial lysis after thrombectomy, large-core treatment, ICH care bundles and evacuation, anticoagulation after ICH, and recovery technologies. Registry status is operational, not evidence of efficacy: “recruiting” means a study is open, and enrollment is planned rather than achieved. Stroke trials face endpoint, timing, imaging, crossover, workflow, and treatment-era drift problems. The useful frontier is less “another intervention” than identifying which biological or system-defined subgroup has a favorable net effect.

How to read this page

ClinicalTrials.gov records below were retrieved live through the v2 API on 2026-08-30. Statuses change; each row should be re-queried before use. PMID-linked completed studies are evidence; NCT-only rows describe protocols or registry state and must not be read as results.

Practice-changing completed trials

Domain Trial Population/selection Decision-changing result Evidence
IV thrombolysis NINDS rt-PA Treatable within 3 h More minimal/no disability despite more symptomatic ICH PMID 7477192
IV thrombolysis ECASS III Selected 3–4.5 h Extended alteplase window PMID 18815396
Tenecteplase AcT Pragmatic thrombolysis-eligible stroke Tenecteplase non-inferior to alteplase PMID 35779553
Thrombectomy MR CLEAN Proximal anterior LVO Modern EVT efficacy PMID 25517348
Thrombectomy HERMES Five early-window trials Common OR 2.49 toward less disability PMID 26898852
Late thrombectomy DAWN Clinical–core mismatch, 6–24 h Functional benefit with tissue selection PMID 29129157
Late thrombectomy DEFUSE 3 Perfusion mismatch, 6–16 h Functional and survival benefit PMID 29364767
ICH blood pressure INTERACT2 Acute spontaneous ICH Neutral dichotomous primary; better ordinal outcome PMID 23713578
Stroke unit Organized inpatient care Mixed stroke Lower death/dependency PMID 32324916
Secondary prevention PROGRESS Prior stroke/TIA Recurrent-stroke reduction with BP lowering PMID 11589932
Minor stroke/TIA CHANCE/POINT Early non-cardioembolic minor event Early recurrence reduction; bleeding constrains duration PMID 23803136; PMID 29766750

The table is a lineage, not a full evidence synthesis; clinical recommendations belong in guidelines.

Active ischemic-stroke reperfusion studies

NCT Registered question Status Planned N Phase
NCT06146790 EVT for distal medium-vessel occlusion Recruiting 564 Not applicable
NCT07185022 Intra-arterial thrombolysis for medium-vessel occlusion Recruiting 282 Not applicable
NCT07557485 EVT for progressive vertebrobasilar occlusion Not yet recruiting 240 Not applicable
NCT05832762 EVT in isolated cervical internal-carotid occlusion Recruiting 200 Not applicable
NCT04667078 P2Y12 inhibition plus thrombectomy in perfusion-selected stroke Recruiting 368 Phase 3
NCT07727395 Intra-arterial alteplase after successful thrombectomy Recruiting 416 Phase 3
NCT06437431 Glenzocimab with EVT in anterior large-core stroke Not yet recruiting 304 Phase 2/3
NCT05789823 Ischemic post-conditioning during thrombectomy Recruiting 160 Phase 2
NCT06801054 Second tenecteplase dose after non-response Not yet recruiting 20 Phase 1
NCT06045156 Early tirofiban after IV thrombolysis Recruiting 1,084 Not applicable

These records were retrieved from the ClinicalTrials.gov v2 API live in this session. The active portfolio shows four recurring strategies: expand vessel targets, improve incomplete microvascular reperfusion, modulate platelets/thrombus after lysis, and protect tissue around the procedure.

Key uncertainties in expansion trials

Expansion Benefit hypothesis Principal harm or design risk
Medium/distal occlusion Rescue eloquent but smaller territories Perforation/hemorrhage and smaller absolute benefit
Large core Prevent further growth despite established injury Edema, hemorrhage, survival with severe disability
Posterior circulation Rescue brainstem tissue Heterogeneous natural history and delayed recognition
Additional thrombolytic/antiplatelet Treat distal thrombi/no-reflow Symptomatic intracranial bleeding
Repeat thrombolytic dose Overcome initial non-response Dose-related hemorrhage with uncertain target engagement

Active intracerebral-hemorrhage studies

NCT Intervention/question Status Planned N Phase
NCT06429332 International ICH care-bundle evaluation Recruiting 3,500 Phase 4
NCT06763055 Intensive prevention of secondary injury (INTERACT5 platform) Recruiting 2,000 Phase 3
NCT05836831 Tranexamic acid in spontaneous ICH Recruiting 3,400 Phase 4
NCT06760078 Tranexamic acid plus intensive BP control ultra-early Not yet recruiting 532 Phase 4
NCT07187687 Early minimally invasive catheter evacuation with thrombolysis Recruiting 750 Not applicable
NCT07471256 Stereotactic puncture plus tenecteplase for lobar ICH Not yet recruiting 636 Phase 3
NCT06402968 Clevidipine BP treatment in acute ICH Recruiting 1,018 Not listed
NCT03243175 Avoiding anticoagulation after ICH Recruiting 300 Phase 3
NCT06587737 Colchicine after acute ICH Not yet recruiting 1,125 Phase 3
NCT05830305 Mobile-health intervention in ICH survivors Recruiting 140 Not applicable

ICH trials increasingly combine early physiological control rather than isolating one drug: blood pressure, fever, glucose, anticoagulant reversal, surgery, and complications may each have modest effects that accumulate. The 2022 guideline characterizes uncertainty across surgery and secondary prevention, but does not validate ongoing trials (Greenberg 2022, PMID 35579034).

Recovery and rehabilitation portfolio

NCT Strategy Status Planned N
NCT03735901 Levodopa-enhanced stroke rehabilitation Active, not recruiting 610
NCT07645586 Lesion-network-guided cTBS for motor recovery Not yet recruiting 584
NCT06876597 Motor-cognitive upper-limb robot rehabilitation Recruiting 1,047
NCT06941961 Intermittent theta-burst stimulation after thrombectomy Recruiting 178
NCT05413733 Internet neuropsychological rehabilitation Active, not recruiting 150
NCT05511285 Sleep and learning during rehabilitation Recruiting 100
NCT04625127 Motor-cognitive gait/falls training Active, not recruiting 76
NCT06906588 Bilateral robotic upper-limb rehabilitation Recruiting 70
NCT06604143 Hand/finger motor recovery intervention Recruiting 40
NCT05898542 Nature-based rehabilitation Recruiting 60

The recovery pipeline is fragmented across small, often unblinded studies with impairment-specific endpoints. Planned enrollment ranges from 40 to 1,047 in the selected rows. Replication, treatment fidelity, achieved dose, and participation outcomes matter more than novelty of hardware (Winstein 2016, PMID 27145936; Bernhardt 2017, PMID 28697708).

Neuroprotection and reperfusion adjuncts

Decades of neuroprotection candidates targeted excitotoxicity, free radicals, inflammation, hypothermia, and conditioning. Preclinical effect size, pretreatment timing, young animals, and infarct-volume endpoints frequently failed to translate to older, comorbid patients treated after onset (Paul 2021, PMID 33144066; Sommer 2017, PMID 28064357). A PubMed update through 2026-08-30 preserved that uncertainty: EnTRIPS found remote ischemic post-conditioning after successful thrombectomy did not improve 90-day independence (60.9% vs 57.8%; adjusted RR 1.07, 95% CI 0.89–1.30), while a 120-patient phase IIb normobaric-hyperoxia trial improved its early neurological endpoint but not the 90-day mRS distribution (adjusted common OR 1.52, 95% CI 0.87–2.63) (Cheng 2026, PMID 42267436; Li 2026, PMID 42403344). These are active mechanistic signals and neutral disability results, not a replicated adjunctive standard.

Modern adjunct trials can improve translation by:

  1. Starting treatment in ambulance or angiography workflow.
  2. Requiring a demonstrable target such as persistent occlusion, no-reflow, or BBB injury.
  3. Measuring pharmacodynamic engagement.
  4. Stratifying by collaterals and reperfusion time.
  5. Prespecifying interaction with reperfusion success.
  6. Using disability and safety rather than infarct volume alone.

NCT05789823 tests post-conditioning in thrombectomy, and NCT06437431 tests a platelet-targeted agent in large-core EVT—examples of embedding adjuncts in successful reperfusion pathways rather than replacing them.

Trial-design constraints

Constraint Distortion Better control
Time-dependent treatment Small workflow delays erase biological benefit Track onset-to-randomization and reperfusion distributions
Open-label procedures Performance and ascertainment bias Blinded centralized outcome assessment
Ordinal disability Dichotomization loses shifts across categories Prespecified ordinal analysis plus interpretable thresholds
Imaging software Different core/mismatch estimates Locked software and threshold sensitivity analyses
Crossover/rescue Dilutes intention-to-treat contrast Report crossover and estimand clearly
Competing death Survivors may have greater measured disability Joint mortality/function reporting
Learning curve Device/operator performance changes during trial Credentialing and temporal analyses
Standard-care drift Control arm improves during enrollment Concurrent controls and rapid recruitment
Small rehabilitation samples Unstable estimates and non-replication Multisite trials and shared core outcomes

HERMES used individual-patient data to demonstrate a common OR 2.49 for lower disability across five thrombectomy trials, an example of harmonized ordinal outcomes increasing precision (Goyal 2016, PMID 26898852). Imaging-selected unknown-onset thrombolysis shows the necessary tradeoff: better function alongside more symptomatic ICH and an imprecise mortality signal (Thomalla 2020, PMID 33176180).

Negative, neutral, and stopped trials are evidence

  • A neutral primary dichotomous endpoint with a positive ordinal analysis, as in INTERACT2, should be reported as discordant rather than “positive” or “negative” (Anderson 2013, PMID 23713578).
  • Non-inferiority depends on the prespecified margin and constancy assumption, not merely a non-significant difference; AcT supports tenecteplase within its pragmatic eligibility and margin (Menon 2022, PMID 35779553).
  • Early stopping for efficacy can exaggerate effects, while stopping for futility can conceal a responsive subgroup.
  • Registry completion without results is not proof of no effect; publication status must be checked separately.

Open questions

  • Which medium/distal occlusions have enough threatened eloquent tissue to justify procedural risk? (NCT06146790; NCT07185022)
  • Does adjunct intra-arterial lysis after successful angiographic reperfusion improve tissue and disability outcomes without unacceptable ICH? (NCT07727395)
  • Can ICH care bundles produce additive functional benefit across health systems? (NCT06429332; Greenberg 2022, PMID 35579034)
  • Which biological state, not just elapsed time, selects a neuroprotective or post-conditioning response? (NCT05789823; Paul 2021, PMID 33144066)
  • Can rehabilitation megatrials preserve individualized dose and fidelity while producing generalizable effects? (NCT06876597; Bernhardt 2017, PMID 28697708)

References

  1. National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. Tissue plasminogen activator for acute ischemic stroke. N Engl J Med. 1995. PMID 7477192
  2. Hacke W, et al. Alteplase 3 to 4.5 hours after acute ischemic stroke. N Engl J Med. 2008. PMID 18815396
  3. Menon BK, et al. Tenecteplase versus alteplase in Canada (AcT). Lancet. 2022. PMID 35779553
  4. Berkhemer OA, et al. Intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015. PMID 25517348
  5. Goyal M, et al. Endovascular thrombectomy individual-patient meta-analysis. Lancet. 2016. PMID 26898852
  6. Nogueira RG, et al. Thrombectomy 6 to 24 hours after stroke. N Engl J Med. 2018. PMID 29129157
  7. Albers GW, et al. Thrombectomy 6 to 16 hours with perfusion selection. N Engl J Med. 2018. PMID 29364767
  8. Thomalla G, et al. Imaging-guided alteplase for unknown-onset stroke. Lancet. 2020. PMID 33176180
  9. Anderson CS, et al. Rapid blood-pressure lowering in acute ICH. N Engl J Med. 2013. PMID 23713578
  10. Greenberg SM, et al. Guideline for spontaneous intracerebral hemorrhage. Stroke. 2022. PMID 35579034
  11. Langhorne P, et al. Organised inpatient stroke-unit care. Cochrane Database Syst Rev. 2020. PMID 32324916
  12. PROGRESS Collaborative Group. Perindopril-based BP lowering after stroke or TIA. Lancet. 2001. PMID 11589932
  13. Wang Y, et al. Clopidogrel with aspirin in minor stroke/TIA. N Engl J Med. 2013. PMID 23803136
  14. Johnston SC, et al. Clopidogrel and aspirin in acute ischemic stroke/high-risk TIA. N Engl J Med. 2018. PMID 29766750
  15. Winstein CJ, et al. Guidelines for adult stroke rehabilitation and recovery. Stroke. 2016. PMID 27145936
  16. Bernhardt J, et al. Standards in stroke recovery research. Int J Stroke. 2017. PMID 28697708
  17. Paul S, et al. Emerging neuroprotective strategies for ischemic stroke. Exp Neurol. 2021. PMID 33144066
  18. Sommer CJ. Ischemic stroke: experimental models and reality. Acta Neuropathol. 2017. PMID 28064357
  19. Cheng Y, et al. Remote ischemic postconditioning in endovascular thrombectomy for stroke: the EnTRIPS randomized clinical trial. Stroke. 2026;57:2276-2286. PMID 42267436
  20. Li W, et al. Adjunctive normobaric hyperoxia with endovascular thrombectomy for acute stroke at 6 to 24 hours: a phase IIb randomized trial. Stroke. 2026;57:2265-2275. PMID 42403344