Ischemic Stroke, Acute Clinical Trial
— MIST-BOfficial title:
Minocycline for Acute Ischemic Stroke Undergoing Endovascular Treatment Due to Basilar Artery Occlusion: a Randomized, Open-label, Proof of Concept Study
This is a prospective, randomized, open-label, evaluator-blinded, single center, proof of concept trial to explore possible beneficial effect of minocycline on acute ischemic stroke (AIS) undergoing endovascular treatment due to basilar artery occlusion (BAO). Minocycline has excellent safety profiles, have been previously demonstrated individually to reduce infarction in animal models of stroke, and have potentially mechanisms of antioxidant, anti-inflammatory, anti-apoptotic and protection of blood-brain barrier. However, it is not known whether minocycline can reduce futile recanalization of endovascular treatment, and improve the outcome of patients with AIS due to BAO. Eligible and willing subjects will be randomly assigned to the treatment group or the control group. The treatment group will receive 200 mg oral minocycline within three hours prior to successful reperfusion, followed by 100 mg every 12 hours times for a total of 5 days. Both groups will receive endovascular thrombectomy and standard medical. The treatment with minocycline will start as soon as possible after diagnosis of stroke. Measures of stroke severity and disability will be recorded at baseline and through the follow-up periods (90 days). The evaluator will be blind to the allocation of patients further minimizing the bias.
| Status | Recruiting |
| Enrollment | 90 |
| Est. completion date | November 30, 2024 |
| Est. primary completion date | November 30, 2024 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: 1. Age = 18 years old. 2. Patients had acute symptoms and signs compatible with ischemia due to basilar artery occlusion (BAO), treated with endovascular therapy. Patients with occlusion of intracranial segments of both vertebral arteries (VA) resulting in no flow to the basilar artery (eg, functional basilar artery occlusion) were also eligible for the study. 3. Last known well to groin puncture between 0 to 24 hours, whether or not patients had thrombolysis with rt-PA. 4. Pre-stroke mRS score of 0-1. 5. Baseline expanded NIHSS (e-NIHSS) score = 6. 6. Signed Informed Consent obtained. 7. Neuroimaging Inclusion Criteria: (1) Proven large vessel occlusion in BAO or VA-V4 occlusion (mTICI score 0-1) determined by MRA or CTA; (2) pc-ASPECTS score = 6 (Non-Contrast CT or DWI); Pons-midbrain-index of<3. Exclusion Criteria: 1. Age<18 years old. 2. Complete cerebellar infarct with significant mass effect or has the imaging features of acute hydrocephalus in NCCT. 3. Intracranial hemorrhage. 4. Previous stroke in the past 90 days; cardiopulmonary resuscitation was performed within 10 days prior to onset. 5. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, INR >3, or platelet<40×109/L. 6. Glucose <2.2 or >22 mmol/L. 7. Systolic blood pressure persistently>185mmHg post-MT despite antihypertensive intervention; Diastolic blood pressure persistently>110mmHg post-MT despite antihypertensive intervention. 8. Acute or chronic renal failure of CKD grade 3-4. 9. Known allergy or hypersensitivity to contrast dye or tetracycline group of drugs. 10. Epileptic seizure at symptom onset. 11. Life expectancy (except for stroke) < 3 months. 12. Female who is pregnancy or breastfeeding, or whom do not use effective contraception at childbearing age. 13. Pre-existing mental illness that interferes with neurological evaluation. 14. Known current participation in another clinical investigation with experimental drug. 15. Unlikely to be available for 90 days follow-up. |
| Country | Name | City | State |
|---|---|---|---|
| China | Department of Neurology, Xijing Hospital, Fourth Military Medical University | Xi'an | Shaanxi |
| Lead Sponsor | Collaborator |
|---|---|
| Xijing Hospital | Central Hospital of Gansu Province, First People's Hospital of Xianyang, Xi'an Gaoxin Hospital, Xi'an No.3 Hospital, Xi'an XD Group Hospital |
China,
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* Note: There are 28 references in all — Click here to view all references
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | The expanded NIH Stroke Scale (e-NIHSS) at 5-7 days or at discharge | The primary effectiveness outcome was the e-NIHSS score at 5-7 days or at discharge. 11-item neurologic examination scale for severity of posterior circulation stroke, adding specific elements in existing items of NIHSS. | 5-7 days or discharge after onset | |
| Primary | Incidence of symptomatic intracranial hemorrhage at 24 hours after treatment | The primary safety outcome was the incidence of symptomatic intracranial hemorrhage, defined as neurological deterioration (=4-point increase on the NIHSS score) within 24 hours after treatment and evidence of intracranial hemorrhage on imaging studies. | 24 hours after treatment | |
| Secondary | mRS at 90 (±14) days | Secondary outcome measure is the degree of disability or dependence at 90 (±14) days as assessed by the mRS scale. The scale runs from 0-6 with "0" being perfect health without symptoms to "6" being death. | 90 (±14) days after onset | |
| Secondary | Good outcome at 90 (±14) days after onset | An mRS score of 0-3 indicated a good outcome, whereas a score of >3 indicated a poor outcome. | 90 (±14) days after onset | |
| Secondary | Favorable outcome at 90 (±14) days after onset | An mRS score of 0-2 indicated a favorable outcome, whereas a score of >2 indicated a poor outcome. | 90 (±14) days after onset | |
| Secondary | Excellent outcome at 90 (±14) days after onset | An mRS score of 0-1 indicated an excellent outcome, whereas a score of >1 indicated a poor outcome | 90 (±14) days after onset | |
| Secondary | NIH Stroke Scale (NIHSS) at 24 hours, 5-7 days or discharge, 30 (±7) days and 90 (±14) days after onset | 11-item neurologic examination scale for severity of stroke. Ratings for each item are scored with 3 to 5 grades. A total NIHSS of 0 is normal; 1-4 is considered a minor stroke; 5-15 moderate; 16-20 moderate to severe; and 21-42 severe. | 90 (±14) days after onset | |
| Secondary | Barthel Index at 30 (±7) days and 90 (±14) days | The Barthel Index (BI) is an ordinal scale used to measure performance in activities of daily living (ADL). The Barthel Index score are scored, a higher number being a reflection of greater ability to function independently following hospital discharge. | 90 (±14) days after onset | |
| Secondary | Incidence of symptomatic intracranial hemorrhage at 3 days after treatment | The secondary safety outcome was the incidence of symptomatic intracranial hemorrhage, defined as neurological deterioration (=4-point increase on the NIHSS score) within 3 days after treatment and evidence of intracranial hemorrhage on imaging studies. | 3 days after treatment | |
| Secondary | Mortality at 90 (±14) days | All-cause mortality occurring within 90 (±14) days follow-up were recorded. | 90 (±14) days after onset | |
| Secondary | Change in infarct volume from baseline to day 5-7 or discharge | Changes of infarct volume from baseline (measured by DWI) to day 5-7 or discharge of stroke onset (measured by Flair). Images are processed by imSTROKE software. | 5-7 days after onset or discharge | |
| Secondary | Length of Intensive Care Unit (ICU) stay and hospital stay | Length of ICU or hospital stay | From the date of admission until discharged from ICU or hospital, up to 4 weeks | |
| Secondary | Pneumonia at 5-7 days or discharge, 30 (±7) days and 90 (±14) days | Determine whether rates of pneumonia are different in the two arms. Rates will be measured as percentages of the entire population at risk. | 90 (±14) days after onset | |
| Secondary | Time of mechanical ventilation or non-invasive ventilation at 5-7 days or at discharge | Determine whether time of mechanical ventilation or non-invasive ventilation are different in the two arms. Rates will be measured as percentages of the entire population at risk. | 5-7 days after onset or discharge | |
| Secondary | Change in hematology assessments: percentage of the lymphocyte subpopulations (%) at 5-7 days or at discharge as compared to Baseline | The percentage of lymphocyte subpopulations in % will be assessed by flow cytometry. | 5-7 days after onset or discharge | |
| Secondary | Change in hematology assessments: matrix metalloproteinase-9 (ng/ml) at 5-7 days or at discharge as compared to Baseline | The level of matrix metalloproteinase-9 in ng/ml will be assessed by ELISA method. | 5-7 days after onset or discharge | |
| Secondary | Change in hematology assessments: IL-6 (pg/ml) at 5-7 days or at discharge as compared to Baseline | The level of IL-6 in pg/ml will be assessed by ELISA method. | 5-7 days after onset or discharge | |
| Secondary | Change in hematology assessments: IL-10 (pg/ml) at 5-7 days or at discharge as compared to Baseline | The level of IL-10 in pg/ml will be assessed by ELISA method. | 5-7 days after onset or discharge | |
| Secondary | Change in hematology assessments: TNF-a (nmol/L) at 5-7 days or at discharge as compared to Baseline | The level of TNF-a in nmol/L will be assessed by ELISA method. | 5-7 days after onset or discharge | |
| Secondary | Change in hematology assessments: leucocytes (x 10^9 /L) at 5-7 days or at discharge as compared to Baseline | Change in the level of leucocytes x 10^9 /L. | 5-7 days after onset or discharge | |
| Secondary | Change in hematology assessments: neutrophilic granulocyte percentage (%) at 5-7 days or at discharge as compared to Baseline | Change in the neutrophilic granulocyte percentage in %. | 5-7 days after onset or discharge | |
| Secondary | Change in hematology assessments: absolute neutrophil value (x 10^9 /L) at 5-7 days or at discharge as compared to Baseline | Change in the level of absolute neutrophil value x 10^9 /L. | 5-7 days after onset or discharge |