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Not yet recruitingNCT06858436SUPERUpdated Apr 3, 2026

SGLT2 Inhibitor Utilization Re-perfusion Therapy

A Phase 4 interventional study of Canagliflozin 100mg in Acute Ischemic Stroke From Large Vessel Occlusion, sponsored by Taichung Veterans General Hospital. Not yet recruiting. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-03.

Sponsored by Taichung Veterans General Hospital · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
150
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

Background:

Reperfusion therapies, including intravenous rt-PA and mechanical thrombectomy, significantly improve outcomes in acute ischemic stroke. However, these interventions also increase the risk of hemorrhagic transformation and malignant edema. Preclinical studies have demonstrated that Canagliflozin, an SGLT2 inhibitor, reduces astrocyte swelling and brain edema in a transient middle cerebral artery occlusion (tMCAo) model. While SGLT2 inhibitors have shown neuroprotective effects in the acute phase of ischemic stroke, their potential to mitigate hemorrhagic transformation and malignant edema following reperfusion therapy in humans remains unexamined.

Aims:

This study aims to evaluate the effect of SGLT2 inhibitors on hemorrhagic transformation and malignant edema in patients undergoing reperfusion therapy for acute ischemic stroke.

Methods:

This is a multi-center, randomized, open-label, controlled study enrolling ischemic stroke patients aged 18 years or older who meet predefined inclusion and exclusion criteria. Participants will be randomized to receive Canagliflozin 100 mg once daily for 14 days or no additional treatment before undergoing mechanical thrombectomy. Clinical data collection will include baseline demographics, medical and medication history, NIHSS scores at admission and 24 hours post-reperfusion, stroke subtype, modified Thrombolysis in Cerebral Infarction (TICI) scores, laboratory results, and modified Rankin Scale (mRS) scores at discharge and 3 months post-stroke.

The primary outcome is to assess the association between Canagliflozin use and the severity of hemorrhagic transformation and malignant edema. Hemorrhagic transformation will be classified using the Heidelberg criteria, and malignant edema will be defined as a midline shift of ≥5 mm. Brain imaging, including CT scans at 24 hours post-intervention and additional scans as clinically indicated, will be reviewed by blinded radiologists. Brain MRA will also be performed to assess infarct size and edema progression.

Importance:

This study aims to explore the potential for repurposing SGLT2 inhibitors as a therapeutic strategy in acute ischemic stroke. If Canagliflozin is shown to reduce hemorrhagic transformation and malignant edema, it could offer a novel adjunctive treatment to improve patient outcomes following reperfusion therapy.

Read the detailed description

Clinical Study Protocol The Role of SGLT2 Inhibitors in Stroke-Reperfusion Injury: A Multi-Center, Randomized, Open-Label, Controlled Trial Version 6.0 \| Date: 2024-12-10

1. Study Overview 1.1 Study Objectives Evaluate the efficacy of Canagliflozin 100 mg daily versus no treatment in reducing hemorrhagic transformation and malignant edema following reperfusion therapy in acute ischemic stroke.

1.2 Study Design

  • Type: Multi-center, randomized, open-label, controlled trial
  • Blinding: Open-label
  • Randomization: Yes
  • Design: Parallel-group
  • Treatment Duration: 14 days
  • Study Period: 3 years (2025-2027)
  • Study Sites: Two medical centers in Taiwan
  • Dose Adjustment: No 1.3 Endpoints

Primary Efficacy Endpoints:

  1. Occurrence of malignant edema
  2. mRS at 3 months post-stroke
  3. Mortality at 3 months

Secondary Efficacy Endpoints:

  1. Hemorrhagic transformation
  2. Parenchymal hematoma type 2
  3. NIHSS at 24 hours
  4. mRS at discharge
  5. EQ-5D at 3 months
  6. Infarct size on MRI
  7. MMP-9 upregulation after EVT

Primary Safety Endpoint:

  • Incidence of adverse events (AEs)

    2. Study Population 2.1 Inclusion Criteria

  • Age ≥18 years
  • Acute ischemic stroke with large vessel occlusion, confirmed by CT perfusion
  • Scheduled for mechanical thrombectomy 2.2 Exclusion Criteria
  • CKD stage 4/5 (eGFR \<30 mL/min/1.73m² or dialysis)
  • Current or recent (≤3 months) SGLT2i use
  • Hypersensitivity to Canagliflozin
  • Type 1 diabetes
  • Pregnancy or lactation 2.3 Withdrawal Criteria
  • Voluntary withdrawal at any time
  • Investigator-initiated withdrawal due to safety concerns or non-compliance

    3. Study Procedures

  • Enrollment: \~105 patients/year (total 315 participants)
  • Randomization: Canagliflozin 100 mg QD vs. control (no treatment) before thrombectomy
  • Assessments:

    o Pre- \& Post-EVT: Arterial blood sampling

    • 24h Post-EVT: Brain dual-energy CT, NIHSS
    • Day 3-Discharge: Brain MRA
    • At Discharge: mRS assessment
    • 3 Months Post-Stroke: mRS, EQ-5D 3.1 Imaging \& Biomarker Analysis
  • Malignant Edema: Midline shift ≥5 mm or symptomatic swelling requiring decompressive craniectomy
  • Hemorrhagic Transformation: Classified by Heidelberg criteria, assessed via CT at 24 hours
  • Infarct Volume: Measured via MRI using the ABC/2 method
  • MMP-9 Analysis: Blood collected pre-/post-EVT, analyzed via ELISA

    4. Safety \& Adverse Event Reporting

  • Physicians will oversee patient safety and medication management.
  • Participants will have direct access to study personnel for AE reporting.
  • AEs will be reported to the IRB per regulatory guidelines. 4.1 Adverse Events (AE) and Management

    1. Hypoglycemia (\~4%)

      • Symptoms: Sweating, confusion, dizziness
      • Management: Monitor blood glucose levels and adjust diabetes medications as needed
    2. Genital Infections (10-11% in women, 4% in men) o Symptoms: Itching, pain, discharge

      o Management: Maintain proper hygiene and use antifungal treatments if necessary

    3. Urinary Tract Infections (UTIs) (\~5%)

      o Symptoms: Painful urination, urgency, fever

      o Management: Increase fluid intake and use antibiotics if symptoms persist

    4. Dehydration (1-2%)

      o Symptoms: Thirst, dark-colored urine, dizziness

      o Management: Stay hydrated and avoid excessive intake of diuretics such as caffeine and alcohol

    5. Hypotension (1-2%) o Symptoms: Dizziness, fainting, fatigue o Management: Monitor blood pressure, stay hydrated, and avoid sudden posture changes

    5. Criteria for Trial Termination

The trial may be stopped if:

  • Safety concerns: Unexpected SAEs or high AE incidence outweighs benefits
  • Regulatory issues: Recommendations from IRB/DSMB
  • Operational issues: Insufficient enrollment or funding
  • Interim analysis: Evidence of harm or lack of benefit

    6. Statistical Considerations 6.1 Sample Size

  • Total required: 314 participants (157 per group)
  • Power: 80%
  • Alpha: 0.1 (one-sided) 6.2 Statistical Analysis
  • Categorical Data: Fisher's exact test or χ² test
  • Continuous Data: Mann-Whitney U-test, independent t-test
  • Kaplan-Meier plots: Cumulative risk analysis
  • Cox Proportional-Hazards Model: Malignant edema \& hemorrhagic transformation incidence
  • Repeated Measures ANOVA: NIHSS score changes
  • Significance:

    o p \< 0.1 (*); p \< 0.05 (**) 6.3 Population for Analysis

  • Intent-to-treat (ITT) for efficacy \& safety assessments 6.4 Data Handling
  • Poor-quality/missing data will be excluded.
  • Protocol deviations will be documented and justified.

    7. Ethical \& Regulatory Considerations 7.1 Ethical Approval \& Patient Rights

  • IRB Approval: Required before initiation
  • Informed Consent: Participants will receive detailed study information and can withdraw at any time
  • Data Security: Encrypted storage at two hospitals, access restricted to investigators 7.2 Data Access
  • IRB permitted access for monitoring, audits, and inspections

    8. Funding \& Insurance

  • Funding: Provided by Veterans General Hospital
  • Insurance: Coverage provided for participants due to study interventions

    9. References Key literature supporting Canagliflozin's neuroprotective potential in ischemic stroke and reperfusion injury.

02

Conditions studied

  • Acute Ischemic Stroke From Large Vessel Occlusion

Browse trials for

Keywords

  • reperfusion therapy
  • SGLT2 inhibitor
  • malignant edema and transformation hemorrhage
03

In context

Anthrax

75 studies on the registry are indexed under Anthrax; 12 are open to participants now.

This study's planned enrollment of 150 is above the median of 100 across 57 interventional studies indexed under Anthrax.

Browse Anthrax studies →

Lead sponsor

Taichung Veterans General Hospital is the lead sponsor of 175 studies on the registry; 39 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Patients must have been diagnosed with acute ischemic stroke and large vessel occlusion by a neurologist, with confirmation supported by CT perfusion scans.
  • Patients must be scheduled to undergo mechanical thrombectomy.

Exclusion criteria

Exclusion Criteria:

  • Patients with have stage 4 or 5 chronic kidney disease (estimated (eGFR) below 30 mL/min/1.73 m² on dialysis)
  • Patients with currently taking an SGLT2i or within 3 months prior to enrollment
  • Patients with a known or allergic reaction to Canagliflozin
  • Patients with type 1 diabetes mellitus
  • Patients with pregnancy or lactation
Terms in these criteria, in plain language(2)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Single group
Masking
None (open label)
Enrollment
150 participants (estimated)

Study arms

  • Experimental
    study group

    Patients who are enrolled will be randomly assigned to either the study group. Receiving Canagliflozin 100mg QD before undergoing mechanical thrombectomy. The prescribed duration of Canagliflozin 100mg QD will be 14 days.

    Drug: Canagliflozin 100mg

  • No intervention
    control group

    Patients who are enrolled will be randomly assigned to either the control group. Not receiving Canagliflozin before undergoing mechanical thrombectomy.

Interventions

06

What researchers measure

Primary outcomes

  1. Occurrence of malignant edema

    Diagnosed if midline shift ≥5 mm on brain imaging or symptomatic brain swelling requiring decompressive craniectomy, leading to in-hospital death, or coma at discharge.

    Time frame: On the 3rd to 5th day for MRI after EVT

  2. mRS at 3rd month after stroke onset

    Assesses health-related quality of life using modified Rankin Scale (mRS) to assess disability level post-stroke for understanding the recovery situation of the patient.

    Time frame: 3 months after stroke onset

  3. Mortality rate at 3rd month after stroke onset

    To understand if the patient is surviving or not after stroke onset.

    Time frame: After stroke onset in 3 months.

Secondary outcomes

  1. Occurrence of hemorrhagic transformation

    Classified using the Heidelberg criteria to categorize hemorrhagic changes post-EVT.

    Time frame: During hospitalization for 14 days

  2. Occurrence f parenchymal hematoma type2

    Identified based on brain imaging and classified using the Heidelberg criteria, indicating severe hemorrhagic transformation.

    Time frame: During hospitalization for 14 days

  3. NIHSS 24 hours later

    Neurological status assessed using National Institutes of Health Stroke Scale (NIHSS) to measure stroke severity and potential deterioration by neurologist.

    Time frame: 24 hours after EVT

  4. mRS at discharge

    Functional outcome evaluated using modified Rankin Scale (mRS) to assess disability level post-stroke.

    Time frame: Day 14 at hospital discharge

  5. EQ-5D at 3rd month after stroke onset

    EQ-5D will be assessed three months after the onset of stroke through either face-to-face interviews or virtual platforms. Assesses health-related quality of life for understanding the recovery situation of the patient.

    Time frame: 3 months after stroke onset

  6. infarct size on brain MRI

    Measured using diffusion-weighted imaging (DWI), defined as a hyperintense area on b = 1000 mm/s² images. Calculation Method: ABC/2 method for infarct volume quantification.

    Time frame: Day 1 after EVT

  7. upregulation of arterial biomarkers (MMP-9) after EVT

    Arterial blood will be collected from the puncture site, in a BD Vacutainer® EDTA tube, before and after EVT and centrifuged at 1,500 × g for 15 min at 4°C. The supernatant was collected as blood plasma. The level of MMP-9 in the plasma was measured following the manufacturer's protocol for the human MMP-9 Quantikine ELISA kit.

    Time frame: Day 1 before EVT is executed and after EVT finished

Other outcomes

  1. Occurrence of adverse events as assessed by CTCAE v5.0

    To understand if the patient have any occurrence of AE or SAE during the session. The result of finding any of the diseases listed on the CTCAE v5.0 will be reported to IRB of Taichung Veterans General Hospital.

    Time frame: During hospitalization for 14 days

07

Study locations

No study locations are listed for this record.

08

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Start is estimated for Apr 2026; primary completion for Oct 2027, 18 months later.

How these figures are worked out, and which studies are left out of them.

Registered
Feb 7, 2025
First posted
Mar 5, 2025
StartEst.
Apr 13, 2026
Primary completionEst.
Oct 31, 2027
CompletionEst.
Oct 31, 2027
Last update
Apr 3, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Apr 3, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT06858436
Responsible party
Po-Lin Chen (Director, Taichung Veterans General Hospital) — Principal investigator
First posted
Mar 5, 2025
Start date
Apr 13, 2026 (estimated)
Primary completion
Oct 31, 2027 (estimated)
Completion
Oct 31, 2027 (estimated)
Last update
Apr 3, 2026

Study contacts

Po-Lin Chen
Contact
boring@mail2000.com.tw
+886 23592525 ext. 3022
Yu-Hsuan Wu
Contact
willie900811@gmail.com
+886 23592525 ext. 3096
Po-Lin Chen
study director · Taichung Veterans General Hospital

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is not yet recruiting, as verified in Mar 2026. You cannot join it, but the record below documents what was studied.

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