Acute StrokePhase 2/3SE-GRACENCT03284463
Safety and Efficacy of Glibenclamide Combined With Rt-PA in Acute Cerebral Embolism
A Phase 2/3 study testing Glibenclamide in people with Acute Stroke, run by Nanfang Hospital, Southern Medical University at 8 sites in China.
Trial summary
This study is designed to evaluate the safety and efficacy of oral glibenclamide in acute ischemic stroke patients who under intravenous rt-PA thrombolysis. Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- Acute Stroke
- What is being tested?
- Glibenclamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 306 participants
- Where
- 8 sitesChina
- Study dates
- 1 Jan 2018to 28 May 2023
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical diagnosis of acute ischemic stroke in the MCA territory (PCA and/or ACA territory involvement in addition to primary MCA territory stroke is acceptable)
- Aged ≥18 and ≤74 years
- A baseline NIHSS score between 4 to 25
- Intravenous rt-PA thrombolysis conducted within 4.5 hours after stroke onset, if known, or the time last seen well [termed "time last known at neurologic baseline" (TLK@B)]
- The time to the start of administration of Study Drug must be ≤10 h after time of symptom onset or TLK@B
- Informed consent was signed by the subject or the legal representative
Who cannot join
- Prior to stroke, significant disability exists, with modified Rankin Scale >1 point
- With medical history or evidence of cerebral hemorrhage, subarachnoid hemorrhage, arteriovenous malformation, cerebral aneurysm or brain tumor
- With clinical or imaging evidence of contralateral cerebral infarction which is believed to have influence on the patient outcome by the investigators
- With clinical or imaging evidence of occlusion in vertebral or basilar artery
- With clinical evidence of brain herniation, e.g., one or two dilated, fixed pupils; unconsciousness (i.e., C2 on item 1a on the NIHSS); and/or loss of other brainstem reflexes, attributable to edema or herniation according to the investigator's judgment
- With gastrointestinal bleeding and instable hemodynamics or other causes that force the patient to stop nutritional support
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- Renal disorder from the patient's history (e.g., dialysis) or eGFR of <60 mL/min/1.73 m2
- Severe liver disease, or ALT >3 times upper limit of normal or bilirubin >2 times normal (subjects may be randomized if liver function tests have been drawn but are not yet available and the subject has no known history of liver disease; however treatment with Study Drug cannot commence until liver function tests are available and indicate ALT >3 times upper limit of normal and bilirubin >2 times upper limit of normal)
- Blood glucose <3.0 mmol/L at enrollment or immediately prior to administration of Study Drug, or a clinically significant history of hypoglycemia
- Acute ST elevation myocardial infarction, and/or acute decompensated heart failure, and/or Tc > 520 ms, and/or known history of cardiac arrest (PEA, VT, VF, asystole), and/or admission for an acute coronary syndrome, myocardial infarction, or coronary intervention within the past 3 months
- Known sulfonylurea treatment within 7 days. Sulfonylureas include glyburide/glibenclamide; glibenclamide plus metformin; Xiaoke Pill (a Chinese patent medicine with main effective constituent of glibenclamide); glimepiride; repaglinide; nateglinide; glipizide; gliclazide; tolbutamide; glibornuride
- Known treatment with bosentan within 7 days
- Known allergy to sulfa or specific allergy to sulfonylurea drugs
- Known G6PD enzyme deficiency
- Pregnant women. Women must be either postmenopausal (as confirmed by the LAR), permanently sterilized or, if ≤50 years old must have a negative test for pregnancy obtained before enrollment
- Breast-feeding women who do not agree (or their LAR does not agree) to stop breastfeeding during Study Drug infusion and for 7 days following the end of Study Drug infusion
- Patients already enrolled in a non-observation-only stroke study, or with life-expectancy <6 months not related to current stroke, or those unlikely to be compliant with follow up
- Patients currently receiving an investigational drug
- Mentally incompetent (prior to qualifying stroke) patients and wards of the state
- Patients who, in the opinion of the investigator, are not suitable for the study (reason to be documented)
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
China8 sites
Huadu District People's Hospital of Guangzhou
Guangzhou, Guangdong, 510515
Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong
Hainan Provincial Hospital of Traditional Chinese Medicine
Haikou, Hainan, 570100
Haikou People's Hospital
Haikou, Hainan, 570208
Heyuan People's Hospital
Heyuan, Guangdong
Maoming People's Hospital
Maoming, Guangdong
Maoming Traditional Chinese Medical Hospital
Maoming, Guangdong
The First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Jiangsu, 325000
About this study
Official title: Safety and Efficacy of Glibenclamide Combined With Rt-PA in Treating Acute Ischemic Stroke: a Prospective, Randomized, Double-blind, Placebo-control, Multi-center Study
This study is designed to evaluate the safety and efficacy of oral glibenclamide in acute ischemic stroke patients who under intravenous rt-PA thrombolysis.
- Conditions
- Acute Stroke
- Being tested
- Glibenclamide, Placebo
- Keywords
- acute ischemic stroke, glibenclamide, rt-PA, blood-brain barrier, brain edema
- Medical subject headings
- Stroke, Ischemic Stroke, Brain Edema
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GlibenclamideDrug
Glibenclamide is administered with a loading dose of 1.25 mg within 10 hours of stroke onset, orally or through gastric tube, followed by 0.625 mg every 8 hour for 5 days.
PlaceboDrug
Placebo is administered with a loading dose of 1.25 mg within 10 hours of stroke onset, orally or through gastric tube, followed by 0.625 mg every 8 hour for 5 days.
| Study group | Role | What they receive |
|---|---|---|
| Glibenclamide | Active comparator | Glibenclamide Tablets Receives: Drug: Glibenclamide |
| Placebo | Placebo comparator | Placebo for Glibenclamide Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional outcome: The proportion of mordified Rankin Scale of 0 to 2 points
The proportion of mordified Rankin Scale of 0 to 2 points at 90 days
Measured: 90 days after the stroke onset
Secondary outcomes (7)
Early improvement: The proportion of NIHSS decreased ≥ 4 points
The proportion of NIHSS decreased ≥ 4 points at 7 days
Measured: 7 days after the stroke onset
Hemorrhagic transformation: The proportion of parenchymal hemorrhagic transformation in cranial CT
The proportion of parenchymal hemorrhagic transformation in cranial CT within 96 hours
Measured: 96 hours after the stroke onset
Midline shift: The proportion of midline shift ≥ 6 mm in cranial CT
The proportion of midline shift ≥ 6 mm in cranial CT within 96 hours
Measured: 96 hours after the stroke onset
Functional outcome 2: The modified Rankin Scale distribution
The modified Rankin Scale distribution at 90 days
Measured: 90 days after the stroke onset
Functional outcome 3: The proportion of Barthel Index of 60-100 points
The proportion of Barthel Index of 60-100 points
Measured: 90 days after the stroke onset
Functional outcome 4: The proportion of IQCODE of ≤ 3.40
The proportion of Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) of ≤ 3.40 at 6 months and 1 year after the stroke onset
Measured: 6 months and 1 year after the stroke onset
Blood-brain barrier: The serum concentration of MMP-9
The serum concentration of MMP-9 at baseline, and at 24, 48, and 72 h
Measured: Baseline, 24, 48, and 72 hours after the stroke onset
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2017
- Study start1 Jan 2018
- Primary completion28 Aug 2022
- Study completion28 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute StrokeStudies of the same condition, open and under way.
- More trials run by Nanfang Hospital, Southern Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 306 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nanfang Hospital, Southern Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Suyue Pan, M.D., Ph.D., Principal investigator, Department of Neurology, Nanfang Hospital, Southern Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03284463
- Sponsor's protocol ID
- NFEC-2017-130
- Acronym
- SE-GRACE
- Status last verified
- Jun 2023
- First submitted
- 14 Sep 2017
- Last updated
- 12 Jun 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Huang K, Zhao X, Zhao Y, Yang G, Zhou S, Yang Z, Huang W, Weng G, Chen P, Duan C, Lin Z, Wang S, Liu X, Huang Y, Zhang J, Zhang X, Li H, Ye S, Gu Y, Zhu M, Chen W, Quan W, Liu N, Chen Q, Chang Y, He J, Ji Z, Wu Y, Pan S; SE-GRACE Collaborators. Safety and efficacy of glibenclamide combined with rtPA in acute cerebral ischemia with occlusion/stenosis of anterior circulation (SE-GRACE): a randomized, double-blind, placebo-controlled trial. EClinicalMedicine. 2023 Nov 1;65:102305. doi: 10.1016/j.eclinm.2023.102305. eCollection 2023 Nov.
PubMed 37965431Huang K, Ji Z, Wu Y, Huang Y, Li G, Zhou S, Yang Z, Huang W, Yang G, Weng G, Chen P, Pan S. Safety and efficacy of glibenclamide combined with rtPA in acute cerebral ischemia with occlusion/stenosis of anterior circulation (SE-GRACE): study protocol for a randomized controlled trial. BMC Neurol. 2020 Jun 11;20(1):239. doi: 10.1186/s12883-020-01823-z.
PubMed 32527232
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Glibenclamide Combined With Rt-PA in Treating Acute Ischemic Stroke: a Prospective, Randomized, Double-blind, Placebo-control, Multi-center Study
- ClinicalTrials.gov ID
- NCT03284463
- Acronym / sponsor ID
- SE-GRACE / NFEC-2017-130
- Conditions
- Acute Stroke
- Keywords
- acute ischemic stroke, glibenclamide, rt-PA, blood-brain barrier, brain edema
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 306 participants (actual)
- Lead sponsor
- Nanfang Hospital, Southern Medical UniversityUniversity, hospital or other
- Study start
- 1 Jan 2018 (actual)
- Primary completion
- 28 Aug 2022 (actual)
- Study completion
- 28 May 2023 (actual)
- First posted
- 15 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to evaluate the safety and efficacy of oral glibenclamide in acute ischemic stroke patients who under intravenous rt-PA thrombolysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Glibenclamide | Active comparator | Drug: GlibenclamideGlibenclamide Tablets |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo for Glibenclamide |
Who may qualify
- Ages
- 18 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Clinical diagnosis of acute ischemic stroke in the MCA territory (PCA and/or ACA territory involvement in addition to primary MCA territory stroke is acceptable)
- Aged ≥18 and ≤74 years
- A baseline NIHSS score between 4 to 25
- Intravenous rt-PA thrombolysis conducted within 4.5 hours after stroke onset, if known, or the time last seen well [termed "time last known at neurologic baseline" (TLK@B)]
- The time to the start of administration of Study Drug must be ≤10 h after time of symptom onset or TLK@B
Key exclusion criteria (20 listed)
- Prior to stroke, significant disability exists, with modified Rankin Scale >1 point
- With medical history or evidence of cerebral hemorrhage, subarachnoid hemorrhage, arteriovenous malformation, cerebral aneurysm or brain tumor
- With clinical or imaging evidence of contralateral cerebral infarction which is believed to have influence on the patient outcome by the investigators
- With clinical or imaging evidence of occlusion in vertebral or basilar artery
- With clinical evidence of brain herniation, e.g., one or two dilated, fixed pupils; unconsciousness (i.e., C2 on item 1a on the NIHSS); and/or loss of other brainstem reflexes, attributable to edema or herniation according to the investigator's judgment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GlibenclamideGlibenclamide is administered with a loading dose of 1.25 mg within 10 hours of stroke onset, orally or through gastric tube, followed by 0.625 mg every 8 hour for 5 days. | Drug | Glibenclamide |
| PlaceboPlacebo is administered with a loading dose of 1.25 mg within 10 hours of stroke onset, orally or through gastric tube, followed by 0.625 mg every 8 hour for 5 days. | Drug | Placebo |
Primary outcome
Functional outcome: The proportion of mordified Rankin Scale of 0 to 2 points
Time frame: 90 days after the stroke onset
The proportion of mordified Rankin Scale of 0 to 2 points at 90 days
7 secondary outcomes
Early improvement: The proportion of NIHSS decreased ≥ 4 points
Time frame: 7 days after the stroke onset
Hemorrhagic transformation: The proportion of parenchymal hemorrhagic transformation in cranial CT
Time frame: 96 hours after the stroke onset
Midline shift: The proportion of midline shift ≥ 6 mm in cranial CT
Time frame: 96 hours after the stroke onset
Functional outcome 2: The modified Rankin Scale distribution
Time frame: 90 days after the stroke onset
Functional outcome 3: The proportion of Barthel Index of 60-100 points
Time frame: 90 days after the stroke onset
Functional outcome 4: The proportion of IQCODE of ≤ 3.40
Time frame: 6 months and 1 year after the stroke onset
Blood-brain barrier: The serum concentration of MMP-9
Time frame: Baseline, 24, 48, and 72 hours after the stroke onset
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2023.
- Derived from this study: PubMed 37965431Huang K, Zhao X, Zhao Y, Yang G, Zhou S, Yang Z, Huang W, Weng G, Chen P, Duan C, Lin Z, Wang S, Liu X, Huang Y, Zhang J, Zhang X, Li H, Ye S, Gu Y, Zhu M, Chen W, Quan W, Liu N, Chen Q, Chang Y, He J, Ji Z, Wu Y, Pan S; SE-GRACE Collaborators. Safety and efficacy of glibenclamide combined with rtPA in acute cerebral ischemia with occlusion/stenosis of anterior circulation (SE-GRACE): a randomized, double-blind, placebo-controlled trial. EClinicalMedicine. 2023 Nov 1;65:102305. doi: 10.1016/j.eclinm.2023.102305. eCollection 2023 Nov.
- Derived from this study: PubMed 32527232Huang K, Ji Z, Wu Y, Huang Y, Li G, Zhou S, Yang Z, Huang W, Yang G, Weng G, Chen P, Pan S. Safety and efficacy of glibenclamide combined with rtPA in acute cerebral ischemia with occlusion/stenosis of anterior circulation (SE-GRACE): study protocol for a randomized controlled trial. BMC Neurol. 2020 Jun 11;20(1):239. doi: 10.1186/s12883-020-01823-z.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Suyue Pan, M.D., Ph.D. principal investigator
Department of Neurology, Nanfang Hospital, Southern Medical University
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Glibenclamide in people with Acute Stroke, run by Nanfang Hospital, Southern Medical University at 8 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional outcome: The proportion of mordified Rankin Scale of 0 to 2 points (time frame: 90 days after the stroke onset). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03284463, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2023.