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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). Two 2026 Chinese phase 3 trials, of loberamisal and of oral edaravone, reported positive 90-day mRS 0–1 results. Neither has been replicated outside China (Li 2026, PMID 42721021; Xiang 2026, PMID 42705987). The live registry on 2026-10-27 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

All 30 original table records were re-fetched through the ClinicalTrials.gov v2 API on 2026-10-27. PROTECT-2 newly changed to completed; the other 29 statuses match the 2026-10-20 snapshot. None has posted results. Historical dates in unchanged rows identify when that change was first recorded. 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.

Selected ischemic-stroke reperfusion studies

NCT Registered question Status Registered N Phase
NCT06146790 EVT for distal medium-vessel occlusion Unknown (2026-10-20; last verified 2024-08, last known 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 Suspended (2026-10-20): registry states futility at prespecified interim analysis, awaiting last patient visit 368 Phase 3
NCT07727395 Intra-arterial alteplase after successful thrombectomy Recruiting 416 Phase 3
NCT06437431 Glenzocimab with EVT in anterior large-core stroke Withdrawn (2026-10-20): sponsor ceased activities; 0 enrolled 304 planned Phase 2/3
NCT05789823 Ischemic post-conditioning during thrombectomy (PROTECT-2) Completed (2026-10-27 check; registry updated 2026-10-21); no posted results 160 actual 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 on 2026-10-27. The selected portfolio shows four recurring strategies: expand vessel targets, improve incomplete microvascular reperfusion, modulate platelets/thrombus after lysis, and protect tissue around the procedure.

Newly published thrombectomy reports awaiting full-text appraisal

LATE-MT and MILD-MT were published on 2026-10-23 (Yang 2026, PMID 42929656; Liu 2026, PMID 42929671). Their ClinicalTrials.gov records are completed with no posted results as of 2026-10-27. The registered questions are thrombectomy at 24–72 hours with perfusion selection (NCT05326932) and thrombectomy within 24 hours for NIHSS <6 with a small core and substantial perfusion mismatch (NCT06179017). Europe PMC lists both articles as subscription-required, and publisher full-text requests failed. Outcome estimates are withheld here until the source tables can be checked; neither registration establishes a general treatment indication.

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 Completed (2026-10-20); 21 actual, completion 2025-07-31; no posted results 150 planned
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 tested post-conditioning in thrombectomy and is now completed (160 actual participants; no posted results on 2026-10-27). Completion does not establish efficacy. NCT06437431, the platelet-targeted large-core EVT trial, was withdrawn before enrollment after its sponsor ceased activities. NCT04667078, the P2Y12 adjunct trial, is suspended; its registry entry reports futility at a prespecified interim analysis, with no publication found in this sweep.

2026 phase 3 neuroprotection results

Two trials from China reported positive results on the excellent-outcome endpoint, which breaks the field's run of neutral disability results. Both need replication before they generalize:

Trial Population Intervention Primary result Boundary
LAIS (32 Chinese hospitals) 997 analyzed; NIHSS 7–20; ≤48 h; age 18–80; pre-stroke mRS ≤1 IV loberamisal 40 mg daily × 10 d vs placebo (PSD-95/α2-GABA-A dual target) mRS 0–1 at 90 d 69.7% vs 56.3%; RR 1.24 (95% CI 1.12–1.36) median NIHSS 8; serious AEs 8.6% vs 10.7%; single-country, single trial (Li 2026, PMID 42721021)
ERASE-STROKE 614; disabling anterior-circulation stroke without reperfusion therapy; ≤24 h oral edaravone (TTYP01) 60 mg twice daily × 28 d vs placebo mRS 0–1 at 90 d 65.4% vs 47.1%; OR 2.12 (95% CI 1.53–2.94) no significant sICH, mortality or serious-AE difference; effect in reperfused patients untested (Xiang 2026, PMID 42705987)

Both effect sizes are large for a single-target neuroprotectant. Both were tested in Chinese populations whose standard care differs from reperfusion-dominant Western pathways. Both figures come from the PubMed abstracts; full texts were not retrievable in the 2026-10-20 sweep (JAMA returned HTTP 403, and the PMC copy has no body). Results from the same period in other adjunct and prevention settings were neutral:

  • STRATEGY (38 Chinese hospitals; 970 patients with MRI-confirmed branch atheromatous disease within 48 h) found that IV tirofiban plus aspirin did not reduce early neurological deterioration within 7 days or new stroke by 90 days versus aspirin alone (17.1% vs 19.6%; HR 0.88, 95% CI 0.65–1.19). Moderate or severe bleeding occurred in 1 of 486 versus 0 (Wang 2026, PMID 42671865; verified in full text).
  • BRANT is the previously unresolved phase III tirofiban report. In the full-analysis set, 90-day mRS 0–1 occurred in 181/258 (70.2%) versus 178/255 (69.8%); adjusted RR 1.00 (95% CI 0.89–1.12). Major bleeding was 0/259 versus 1/245 among participants with available safety assessments. The tested regimen used tirofiban without concomitant oral antiplatelets during infusion and excluded thrombolysis/EVT recipients. The neutral superiority result does not establish equivalence or the effects of earlier initiation or overlapping oral-antiplatelet regimens (Li 2026, PMID 42894564; full text, Table 2).
  • Colchicine after ICH, pilot (11 Canadian centers; 100 participants randomized ≤48 h after ICH): recruitment was 8.9 participants per site-year and 6-month retention 92%. Permanent study-drug discontinuation reached 27% in both arms, and exploratory efficacy and safety did not differ over a median 364 days (Katsanos 2026, PMID 42558067; verified in full text). This is a feasibility result that informs the phase 3 registration NCT06587737, not efficacy evidence.

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)
  • Do the LAIS and ERASE-STROKE effects replicate outside China, in patients who also receive thrombolysis or thrombectomy, and on the full ordinal mRS (Li 2026, PMID 42721021; Xiang 2026, PMID 42705987)?
  • 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
  21. Li S, et al. Loberamisal for acute ischemic stroke: the LAIS randomized clinical trial. JAMA. 2026. PMID 42721021
  22. Xiang Y, et al. Early and prolonged oral edaravone for neuroprotection in acute ischemic stroke: the ERASE-STROKE randomized controlled phase 3 trial. Sci Bull (Beijing). 2026;71:4790-4799. PMID 42705987
  23. Wang Y, et al. Tirofiban for branch atheromatous disease-related stroke: the STRATEGY randomized clinical trial. JAMA Neurol. 2026;83:956-964. PMID 42671865
  24. Katsanos AH, et al. Colchicine for the prevention of vascular events after an acute intracerebral hemorrhage: a placebo-controlled trial. Stroke. 2026;57:2971-2980. PMID 42558067
  25. Yang P, et al. Mechanical Thrombectomy 24 to 72 Hours after Large-Vessel Ischemic Stroke. N Engl J Med. 2026. PMID 42929656
  26. Liu J, et al. Trial of Endovascular Therapy for Mild Stroke with Large-Vessel Occlusion. N Engl J Med. 2026. PMID 42929671
  27. Li S, et al. Tirofiban vs standard antiplatelet therapy in acute branch atheromatous disease-related stroke: a multicenter, randomized, open-label, blinded-endpoint, parallel-group, phase III clinical trial. Lancet Reg Health West Pac. 2026;75:101995. PMID 42894564