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| Name | Class |
|---|---|
| Xi'an No.3 Hospital | OTHER_GOV |
| Xi'an Gaoxin Hospital | OTHER |
| First People's Hospital of Xianyang | OTHER |
| Xi'an XD Group Hospital |
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This is a multi-center, evaluator-blinded, randomized, open-label, proof of concept trial to explore possible beneficial effect of adjunctive oral 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, 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 randomization. Considering the risk of difficulty in feeding tube before EVT, minocycline administered within one hours after EVT is acceptable. 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment group | Experimental | Patients randomized to the treatment group will receive oral minocycline in addition to endovascular treatment and other standard medical. The first dose of minocycline will be administered 200 mg orally, followed by 100 mg every 12 hours times for a total of 5 days. After randomization, oral minocycline should be given as soon as possible before the EVT treatment. If vomiting occurs within half an hour of the first dose, the clinician should assess the necessary of re-administering 100mg based on the severity of vomiting. If the patient is considered to be at any risk for aspiration or is unable to swallow based on swallowing evaluation, study drug will be oral via feeding tube. Considering the risk of difficulty in feeding tube before EVT, minocycline administered within one hours after EVT is acceptable. |
|
| Control group | No Intervention | Patients randomized to the control group will receive endovascular treatment and other standard treatment, without minocycline treatment. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Minocycline | Drug | 200 mg minocycline orally or via feeding tube, followed by 100 mg every 12 hours times for a total of 5 days. If vomiting occurs within half an hour of the first dose, the clinician should assess the necessary of re-administering 100mg based on the severity of vomiting. Considering the risk of difficulty in feeding tube before EVT, minocycline administered within one hours after EVT is acceptable. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Incidence of symptomatic intracranial hemorrhage at 24 hours from randomization | 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 from randomization and evidence of intracranial hemorrhage on imaging studies. | 24 hours from randomization |
| Measure | Description | Time Frame |
|---|---|---|
| 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 from randomization |
| Good outcome at 90 (±14) days from randomization |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Neurology, Xijing Hospital, Fourth Military Medical University | Xi'an | Shaanxi | 710032 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31662037 | Background | Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL. Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2019 Dec;50(12):e344-e418. doi: 10.1161/STR.0000000000000211. Epub 2019 Oct 30. | |
| 25106063 |
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| ID | Term |
|---|---|
| D000083242 | Ischemic Stroke |
| C562573 | cyclopia sequence |
| ID | Term |
|---|---|
| D020521 | Stroke |
| D002561 | Cerebrovascular Disorders |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
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Not provided
| ID | Term |
|---|---|
| D008911 | Minocycline |
| ID | Term |
|---|---|
| D013754 | Tetracyclines |
| D009279 | Naphthacenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
Not provided
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| UNKNOWN |
| Central Hospital of Gansu Province | UNKNOWN |
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All study staff is not masked to randomization except the following: independent outcome assessor and statistician.
|
|
An mRS score of 0-3 indicated a good outcome, whereas a score of >3 indicated a poor outcome. |
| 90 (±14) days from randomization |
| Favorable outcome at 90 (±14) days from randomization | An mRS score of 0-2 indicated a favorable outcome, whereas a score of >2 indicated a poor outcome. | 90 (±14) days from randomization |
| Excellent outcome at 90 (±14) days from randomization | An mRS score of 0-1 indicated an excellent outcome, whereas a score of >1 indicated a poor outcome | 90 (±14) days from randomization |
| NIH Stroke Scale (NIHSS) at 24 hours, 5-7 days or discharge, 30 (±7) days and 90 (±14) days from randomization | 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 from randomization |
| Modified Barthel Index at 30 (±7) days and 90 (±14) days | The modified Barthel Index (mBI) 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. | 30 (±7) days and 90 (±14) days from randomization |
| Incidence of symptomatic intracranial hemorrhage at 3 days from randomization | 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 from randomization and evidence of intracranial hemorrhage on imaging studies. | 3 days from randomization |
| Mortality at 90 (±14) days from randomization | All-cause mortality occurring within 90 (±14) days follow-up were recorded. | 90 (±14) days from randomization |
| 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 from randomization or discharge |
| 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 |
| 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 from randomization |
| 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 from randomization or discharge |
| 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 from randomization or discharge |
| 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 from randomization or discharge |
| 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 from randomization or discharge |
| 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 from randomization or discharge |
| Change in hematology assessments: TNF-α (nmol/L) at 5-7 days or at discharge as compared to Baseline | The level of TNF-α in nmol/L will be assessed by ELISA method. | 5-7 days from randomization or discharge |
| 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 from randomization or discharge |
| 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 from randomization or discharge |
| 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 from randomization or discharge |
| Background |
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| 34774198 | Background | Jovin TG, Nogueira RG, Lansberg MG, Demchuk AM, Martins SO, Mocco J, Ribo M, Jadhav AP, Ortega-Gutierrez S, Hill MD, Lima FO, Haussen DC, Brown S, Goyal M, Siddiqui AH, Heit JJ, Menon BK, Kemp S, Budzik R, Urra X, Marks MP, Costalat V, Liebeskind DS, Albers GW. Thrombectomy for anterior circulation stroke beyond 6 h from time last known well (AURORA): a systematic review and individual patient data meta-analysis. Lancet. 2022 Jan 15;399(10321):249-258. doi: 10.1016/S0140-6736(21)01341-6. Epub 2021 Nov 11. |
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| 20075087 | Background | Hussein HM, Georgiadis AL, Vazquez G, Miley JT, Memon MZ, Mohammad YM, Christoforidis GA, Tariq N, Qureshi AI. Occurrence and predictors of futile recanalization following endovascular treatment among patients with acute ischemic stroke: a multicenter study. AJNR Am J Neuroradiol. 2010 Mar;31(3):454-8. doi: 10.3174/ajnr.A2006. Epub 2010 Jan 14. |
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| 32087818 | Background | Hill MD, Goyal M, Menon BK, Nogueira RG, McTaggart RA, Demchuk AM, Poppe AY, Buck BH, Field TS, Dowlatshahi D, van Adel BA, Swartz RH, Shah RA, Sauvageau E, Zerna C, Ospel JM, Joshi M, Almekhlafi MA, Ryckborst KJ, Lowerison MW, Heard K, Garman D, Haussen D, Cutting SM, Coutts SB, Roy D, Rempel JL, Rohr AC, Iancu D, Sahlas DJ, Yu AYX, Devlin TG, Hanel RA, Puetz V, Silver FL, Campbell BCV, Chapot R, Teitelbaum J, Mandzia JL, Kleinig TJ, Turkel-Parrella D, Heck D, Kelly ME, Bharatha A, Bang OY, Jadhav A, Gupta R, Frei DF, Tarpley JW, McDougall CG, Holmin S, Rha JH, Puri AS, Camden MC, Thomalla G, Choe H, Phillips SJ, Schindler JL, Thornton J, Nagel S, Heo JH, Sohn SI, Psychogios MN, Budzik RF, Starkman S, Martin CO, Burns PA, Murphy S, Lopez GA, English J, Tymianski M; ESCAPE-NA1 Investigators. Efficacy and safety of nerinetide for the treatment of acute ischaemic stroke (ESCAPE-NA1): a multicentre, double-blind, randomised controlled trial. Lancet. 2020 Mar 14;395(10227):878-887. doi: 10.1016/S0140-6736(20)30258-0. Epub 2020 Feb 20. |
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| D009422 |
| Nervous System Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D006844 |
| Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |