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Minocycline for Acute Ischemic Stroke Undergoing Endovascular Treatment Due to Basilar Artery Occlusion (MIST-B) (MIST-B)

Primary Purpose

Ischemic Stroke, Acute, Minocycline, Endovascular Treatment

Status

Recruiting

Phase

Phase 4

Locations

China

Study Type

Interventional

Intervention

Minocycline

About this trial

This is an interventional treatment trial for Ischemic Stroke, Acute focused on measuring Ischemic Stroke, Basilar Artery Occlusion, Endovascular Treatment, Minocycline, Neuroprotection, Futile Recanalization

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age ≥ 18 years old.
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.
Last known well to groin puncture between 0 to 24 hours, whether or not patients had thrombolysis with rt-PA.
Pre-stroke mRS score of 0-1.
Baseline expanded NIHSS (e-NIHSS) score ≥ 6.
Signed Informed Consent obtained.
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:

Age<18 years old.
Complete cerebellar infarct with significant mass effect or has the imaging features of acute hydrocephalus in NCCT.
Intracranial hemorrhage.
Previous stroke in the past 90 days; cardiopulmonary resuscitation was performed within 10 days prior to onset.
Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, INR >3, or platelet<40×109/L.
Glucose <2.2 or >22 mmol/L.
Systolic blood pressure persistently>185mmHg post-MT despite antihypertensive intervention; Diastolic blood pressure persistently>110mmHg post-MT despite antihypertensive intervention.
Acute or chronic renal failure of CKD grade 3-4.
Known allergy or hypersensitivity to contrast dye or tetracycline group of drugs.
Epileptic seizure at symptom onset.
Life expectancy (except for stroke) < 3 months.
Female who is pregnancy or breastfeeding, or whom do not use effective contraception at childbearing age.
Pre-existing mental illness that interferes with neurological evaluation.
Known current participation in another clinical investigation with experimental drug.
Unlikely to be available for 90 days follow-up.

Sites / Locations

Department of Neurology, Xijing Hospital, Fourth Military Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Treatment group

Control group

Arm Description

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 prior to successful reperfusion, 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. 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.

Patients randomized to the control group will receive endovascular treatment and other standard treatment, without minocycline treatment.

Outcomes

Primary Outcome Measures

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.

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.

Secondary Outcome Measures

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.

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.

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.

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

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.

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.

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.

Mortality at 90 (±14) days

All-cause mortality occurring within 90 (±14) days follow-up were recorded.

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.

Length of Intensive Care Unit (ICU) stay and hospital stay

Length of ICU or hospital stay

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.

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.

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.

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.

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.

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.

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.

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.

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 %.

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.

Full Information

NCT ID

NCT05512910

First Posted

August 18, 2022

Last Updated

December 13, 2022

Sponsor

Xijing Hospital

Collaborators

Xi'an No.3 Hospital, Xi'an Gaoxin Hospital, First People's Hospital of Xianyang, Xi'an XD Group Hospital, Central Hospital of Gansu Province

1. Study Identification

Unique Protocol Identification Number

NCT05512910

Brief Title

Minocycline for Acute Ischemic Stroke Undergoing Endovascular Treatment Due to Basilar Artery Occlusion (MIST-B)

Acronym

MIST-B

Official Title

Minocycline for Acute Ischemic Stroke Undergoing Endovascular Treatment Due to Basilar Artery Occlusion: a Randomized, Open-label, Proof of Concept Study

Study Type

Interventional

2. Study Status

Record Verification Date

December 2022

Overall Recruitment Status

Recruiting

Study Start Date

December 13, 2022 (Anticipated)

Primary Completion Date

November 30, 2024 (Anticipated)

Study Completion Date

November 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Xijing Hospital

Collaborators

Xi'an No.3 Hospital, Xi'an Gaoxin Hospital, First People's Hospital of Xianyang, Xi'an XD Group Hospital, Central Hospital of Gansu Province

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Ischemic Stroke, Acute, Minocycline, Endovascular Treatment, Basilar Artery Occlusion

Keywords

Ischemic Stroke, Basilar Artery Occlusion, Endovascular Treatment, Minocycline, Neuroprotection, Futile Recanalization

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Masking Description

All study staff is not masked to randomization except the following: independent outcome assessor and statistician.

Allocation

Randomized

Enrollment

90 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment group

Arm Type

Experimental

Arm Description

Arm Title

Control group

Arm Type

No Intervention

Arm Description

Patients randomized to the control group will receive endovascular treatment and other standard treatment, without minocycline treatment.

Intervention Type

Drug

Intervention Name(s)

Minocycline

Other Intervention Name(s)

Minocycline hydrochloride

Intervention Description

200 mg minocycline orally or via nasogastric tube prior to successful reperfusion, 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.

Primary Outcome Measure Information:

Title

The expanded NIH Stroke Scale (e-NIHSS) at 5-7 days or at discharge

Description

Time Frame

5-7 days or discharge after onset

Title

Incidence of symptomatic intracranial hemorrhage at 24 hours after treatment

Description

Time Frame

24 hours after treatment

Secondary Outcome Measure Information:

Title

mRS at 90 (±14) days

Description

Time Frame

90 (±14) days after onset

Title

Good outcome at 90 (±14) days after onset

Description

An mRS score of 0-3 indicated a good outcome, whereas a score of >3 indicated a poor outcome.

Time Frame

90 (±14) days after onset

Title

Favorable outcome at 90 (±14) days after onset

Description

An mRS score of 0-2 indicated a favorable outcome, whereas a score of >2 indicated a poor outcome.

Time Frame

90 (±14) days after onset

Title

Excellent outcome at 90 (±14) days after onset

Description

An mRS score of 0-1 indicated an excellent outcome, whereas a score of >1 indicated a poor outcome

Time Frame

90 (±14) days after onset

Title

NIH Stroke Scale (NIHSS) at 24 hours, 5-7 days or discharge, 30 (±7) days and 90 (±14) days after onset

Description

Time Frame

90 (±14) days after onset

Title

Barthel Index at 30 (±7) days and 90 (±14) days

Description

Time Frame

90 (±14) days after onset

Title

Incidence of symptomatic intracranial hemorrhage at 3 days after treatment

Description

Time Frame

3 days after treatment

Title

Mortality at 90 (±14) days

Description

All-cause mortality occurring within 90 (±14) days follow-up were recorded.

Time Frame

90 (±14) days after onset

Title

Change in infarct volume from baseline to day 5-7 or discharge

Description

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.

Time Frame

5-7 days after onset or discharge

Title

Length of Intensive Care Unit (ICU) stay and hospital stay

Description

Length of ICU or hospital stay

Time Frame

From the date of admission until discharged from ICU or hospital, up to 4 weeks

Title

Pneumonia at 5-7 days or discharge, 30 (±7) days and 90 (±14) days

Description

Determine whether rates of pneumonia are different in the two arms. Rates will be measured as percentages of the entire population at risk.

Time Frame

90 (±14) days after onset

Title

Time of mechanical ventilation or non-invasive ventilation at 5-7 days or at discharge

Description

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.

Time Frame

5-7 days after onset or discharge

Title

Change in hematology assessments: percentage of the lymphocyte subpopulations (%) at 5-7 days or at discharge as compared to Baseline

Description

The percentage of lymphocyte subpopulations in % will be assessed by flow cytometry.

Time Frame

5-7 days after onset or discharge

Title

Change in hematology assessments: matrix metalloproteinase-9 (ng/ml) at 5-7 days or at discharge as compared to Baseline

Description

The level of matrix metalloproteinase-9 in ng/ml will be assessed by ELISA method.

Time Frame

5-7 days after onset or discharge

Title

Change in hematology assessments: IL-6 (pg/ml) at 5-7 days or at discharge as compared to Baseline

Description

The level of IL-6 in pg/ml will be assessed by ELISA method.

Time Frame

5-7 days after onset or discharge

Title

Change in hematology assessments: IL-10 (pg/ml) at 5-7 days or at discharge as compared to Baseline

Description

The level of IL-10 in pg/ml will be assessed by ELISA method.

Time Frame

5-7 days after onset or discharge

Title

Change in hematology assessments: TNF-α (nmol/L) at 5-7 days or at discharge as compared to Baseline

Description

The level of TNF-α in nmol/L will be assessed by ELISA method.

Time Frame

5-7 days after onset or discharge

Title

Change in hematology assessments: leucocytes (x 10^9 /L) at 5-7 days or at discharge as compared to Baseline

Description

Change in the level of leucocytes x 10^9 /L.

Time Frame

5-7 days after onset or discharge

Title

Change in hematology assessments: neutrophilic granulocyte percentage (%) at 5-7 days or at discharge as compared to Baseline

Description

Change in the neutrophilic granulocyte percentage in %.

Time Frame

5-7 days after onset or discharge

Title

Change in hematology assessments: absolute neutrophil value (x 10^9 /L) at 5-7 days or at discharge as compared to Baseline

Description

Change in the level of absolute neutrophil value x 10^9 /L.

Time Frame

5-7 days after onset or discharge

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age ≥ 18 years old. 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. Last known well to groin puncture between 0 to 24 hours, whether or not patients had thrombolysis with rt-PA. Pre-stroke mRS score of 0-1. Baseline expanded NIHSS (e-NIHSS) score ≥ 6. Signed Informed Consent obtained. 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: Age<18 years old. Complete cerebellar infarct with significant mass effect or has the imaging features of acute hydrocephalus in NCCT. Intracranial hemorrhage. Previous stroke in the past 90 days; cardiopulmonary resuscitation was performed within 10 days prior to onset. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, INR >3, or platelet<40×109/L. Glucose <2.2 or >22 mmol/L. Systolic blood pressure persistently>185mmHg post-MT despite antihypertensive intervention; Diastolic blood pressure persistently>110mmHg post-MT despite antihypertensive intervention. Acute or chronic renal failure of CKD grade 3-4. Known allergy or hypersensitivity to contrast dye or tetracycline group of drugs. Epileptic seizure at symptom onset. Life expectancy (except for stroke) < 3 months. Female who is pregnancy or breastfeeding, or whom do not use effective contraception at childbearing age. Pre-existing mental illness that interferes with neurological evaluation. Known current participation in another clinical investigation with experimental drug. Unlikely to be available for 90 days follow-up.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Wen Jiang, Ph.D

Phone

86-029-84771319

jiangwen@fmmu.edu.cn

First Name & Middle Initial & Last Name or Official Title & Degree

Dong Wei, Ph.D

Phone

86-029-84771319

weieast@fmmu.edu.cn

Facility Information:

Facility Name

Department of Neurology, Xijing Hospital, Fourth Military Medical University

City

Xi'an

State/Province

Shaanxi

ZIP/Postal Code

710032

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Wen Jiang, PhD

Phone

86-029-84771319

jiangwen@fmmu.edu.cn

First Name & Middle Initial & Last Name & Degree

Dong Wei, PhD

Phone

86-029-84771319

weieast@fmmu.edu.cn

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

31662037

Citation

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. Erratum In: Stroke. 2019 Dec;50(12):e440-e441.

Results Reference

background

PubMed Identifier

25106063

Citation

Emberson J, Lees KR, Lyden P, Blackwell L, Albers G, Bluhmki E, Brott T, Cohen G, Davis S, Donnan G, Grotta J, Howard G, Kaste M, Koga M, von Kummer R, Lansberg M, Lindley RI, Murray G, Olivot JM, Parsons M, Tilley B, Toni D, Toyoda K, Wahlgren N, Wardlaw J, Whiteley W, del Zoppo GJ, Baigent C, Sandercock P, Hacke W; Stroke Thrombolysis Trialists' Collaborative Group. Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials. Lancet. 2014 Nov 29;384(9958):1929-35. doi: 10.1016/S0140-6736(14)60584-5. Epub 2014 Aug 5.

Results Reference

background

PubMed Identifier

34774198

Citation

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.

Results Reference

background

PubMed Identifier

35387858

Citation

Zhao Y, Zhao W, Guo Y, Li Y. Endovascular thrombectomy versus standard medical treatment for stroke patients with acute basilar artery occlusion: a systematic review and meta-analysis. J Neurointerv Surg. 2022 Dec;14(12):1173-1179. doi: 10.1136/neurintsurg-2022-018680. Epub 2022 Apr 6.

Results Reference

background

PubMed Identifier

20075087

Citation

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.

Results Reference

background

PubMed Identifier

26898852

Citation

Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Davalos A, Majoie CB, van der Lugt A, de Miquel MA, Donnan GA, Roos YB, Bonafe A, Jahan R, Diener HC, van den Berg LA, Levy EI, Berkhemer OA, Pereira VM, Rempel J, Millan M, Davis SM, Roy D, Thornton J, Roman LS, Ribo M, Beumer D, Stouch B, Brown S, Campbell BC, van Oostenbrugge RJ, Saver JL, Hill MD, Jovin TG; HERMES collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet. 2016 Apr 23;387(10029):1723-31. doi: 10.1016/S0140-6736(16)00163-X. Epub 2016 Feb 18.

Results Reference

background

PubMed Identifier

32087818

Citation

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.

Results Reference

background

PubMed Identifier

21738161

Citation

Iadecola C, Anrather J. The immunology of stroke: from mechanisms to translation. Nat Med. 2011 Jul 7;17(7):796-808. doi: 10.1038/nm.2399.

Results Reference

background

PubMed Identifier

35079135

Citation

Fisher M, Savitz SI. Pharmacological brain cytoprotection in acute ischaemic stroke - renewed hope in the reperfusion era. Nat Rev Neurol. 2022 Apr;18(4):193-202. doi: 10.1038/s41582-021-00605-6. Epub 2022 Jan 25.

Results Reference

background

PubMed Identifier

29770166

Citation

Sun MS, Jin H, Sun X, Huang S, Zhang FL, Guo ZN, Yang Y. Free Radical Damage in Ischemia-Reperfusion Injury: An Obstacle in Acute Ischemic Stroke after Revascularization Therapy. Oxid Med Cell Longev. 2018 Jan 31;2018:3804979. doi: 10.1155/2018/3804979. eCollection 2018.

Results Reference

background

PubMed Identifier

25598025

Citation

Bai J, Lyden PD. Revisiting cerebral postischemic reperfusion injury: new insights in understanding reperfusion failure, hemorrhage, and edema. Int J Stroke. 2015 Feb;10(2):143-52. doi: 10.1111/ijs.12434.

Results Reference

background

PubMed Identifier

32391806

Citation

Iadecola C, Buckwalter MS, Anrather J. Immune responses to stroke: mechanisms, modulation, and therapeutic potential. J Clin Invest. 2020 Jun 1;130(6):2777-2788. doi: 10.1172/JCI135530.

Results Reference

background

PubMed Identifier

26786115

Citation

De Meyer SF, Denorme F, Langhauser F, Geuss E, Fluri F, Kleinschnitz C. Thromboinflammation in Stroke Brain Damage. Stroke. 2016 Apr;47(4):1165-72. doi: 10.1161/STROKEAHA.115.011238. Epub 2016 Jan 19. No abstract available.

Results Reference

background

PubMed Identifier

10799911

Citation

Schafer MK, Schwaeble WJ, Post C, Salvati P, Calabresi M, Sim RB, Petry F, Loos M, Weihe E. Complement C1q is dramatically up-regulated in brain microglia in response to transient global cerebral ischemia. J Immunol. 2000 May 15;164(10):5446-52. doi: 10.4049/jimmunol.164.10.5446.

Results Reference

background

PubMed Identifier

15674236

Citation

Koistinaho M, Malm TM, Kettunen MI, Goldsteins G, Starckx S, Kauppinen RA, Opdenakker G, Koistinaho J. Minocycline protects against permanent cerebral ischemia in wild type but not in matrix metalloprotease-9-deficient mice. J Cereb Blood Flow Metab. 2005 Apr;25(4):460-7. doi: 10.1038/sj.jcbfm.9600040.

Results Reference

background

PubMed Identifier

26303850

Citation

Fu Y, Liu Q, Anrather J, Shi FD. Immune interventions in stroke. Nat Rev Neurol. 2015 Sep;11(9):524-35. doi: 10.1038/nrneurol.2015.144. Epub 2015 Aug 25.

Results Reference

background

PubMed Identifier

10406406

Citation

Elkayam O, Yaron M, Caspi D. Minocycline-induced autoimmune syndromes: an overview. Semin Arthritis Rheum. 1999 Jun;28(6):392-7. doi: 10.1016/s0049-0172(99)80004-3.

Results Reference

background

PubMed Identifier

4199710

Citation

Macdonald H, Kelly RG, Allen ES, Noble JF, Kanegis LA. Pharmacokinetic studies on minocycline in man. Clin Pharmacol Ther. 1973 Sep-Oct;14(5):852-61. doi: 10.1002/cpt1973145852. No abstract available.

Results Reference

background

PubMed Identifier

15556807

Citation

Yong VW, Wells J, Giuliani F, Casha S, Power C, Metz LM. The promise of minocycline in neurology. Lancet Neurol. 2004 Dec;3(12):744-51. doi: 10.1016/S1474-4422(04)00937-8.

Results Reference

background

PubMed Identifier

34646382

Citation

Yamasaki T, Hatori A, Zhang Y, Mori W, Kurihara Y, Ogawa M, Wakizaka H, Rong J, Wang L, Liang S, Zhang MR. Neuroprotective effects of minocycline and KML29, a potent inhibitor of monoacylglycerol lipase, in an experimental stroke model: a small-animal positron emission tomography study. Theranostics. 2021 Sep 13;11(19):9492-9502. doi: 10.7150/thno.64320. eCollection 2021.

Results Reference

background

PubMed Identifier

30626393

Citation

Yew WP, Djukic ND, Jayaseelan JSP, Walker FR, Roos KAA, Chataway TK, Muyderman H, Sims NR. Early treatment with minocycline following stroke in rats improves functional recovery and differentially modifies responses of peri-infarct microglia and astrocytes. J Neuroinflammation. 2019 Jan 9;16(1):6. doi: 10.1186/s12974-018-1379-y.

Results Reference

background

PubMed Identifier

21659333

Citation

Sancho M, Herrera AE, Gortat A, Carbajo RJ, Pineda-Lucena A, Orzaez M, Perez-Paya E. Minocycline inhibits cell death and decreases mutant Huntingtin aggregation by targeting Apaf-1. Hum Mol Genet. 2011 Sep 15;20(18):3545-53. doi: 10.1093/hmg/ddr271. Epub 2011 Jun 9.

Results Reference

background

PubMed Identifier

26165350

Citation

Wu Y, Chen Y, Wu Q, Jia L, Du X. Minocycline inhibits PARP-1 expression and decreases apoptosis in diabetic retinopathy. Mol Med Rep. 2015 Oct;12(4):4887-94. doi: 10.3892/mmr.2015.4064. Epub 2015 Jul 8.

Results Reference

background

PubMed Identifier

28204513

Citation

Dai C, Ciccotosto GD, Cappai R, Wang Y, Tang S, Xiao X, Velkov T. Minocycline attenuates colistin-induced neurotoxicity via suppression of apoptosis, mitochondrial dysfunction and oxidative stress. J Antimicrob Chemother. 2017 Jun 1;72(6):1635-1645. doi: 10.1093/jac/dkx037.

Results Reference

background

PubMed Identifier

17909152

Citation

Lampl Y, Boaz M, Gilad R, Lorberboym M, Dabby R, Rapoport A, Anca-Hershkowitz M, Sadeh M. Minocycline treatment in acute stroke: an open-label, evaluator-blinded study. Neurology. 2007 Oct 2;69(14):1404-10. doi: 10.1212/01.wnl.0000277487.04281.db.

Results Reference

background

PubMed Identifier

25155474

Citation

Amiri-Nikpour MR, Nazarbaghi S, Hamdi-Holasou M, Rezaei Y. An open-label evaluator-blinded clinical study of minocycline neuroprotection in ischemic stroke: gender-dependent effect. Acta Neurol Scand. 2015 Jan;131(1):45-50. doi: 10.1111/ane.12296. Epub 2014 Aug 23.

Results Reference

background

PubMed Identifier

22406775

Citation

Padma Srivastava MV, Bhasin A, Bhatia R, Garg A, Gaikwad S, Prasad K, Singh MB, Tripathi M. Efficacy of minocycline in acute ischemic stroke: a single-blinded, placebo-controlled trial. Neurol India. 2012 Jan-Feb;60(1):23-8. doi: 10.4103/0028-3886.93584.

Results Reference

background

PubMed Identifier

23868273

Citation

Kohler E, Prentice DA, Bates TR, Hankey GJ, Claxton A, van Heerden J, Blacker D. Intravenous minocycline in acute stroke: a randomized, controlled pilot study and meta-analysis. Stroke. 2013 Sep;44(9):2493-9. doi: 10.1161/STROKEAHA.113.000780. Epub 2013 Jul 18.

Results Reference

background

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Minocycline for Acute Ischemic Stroke Undergoing Endovascular Treatment Due to Basilar Artery Occlusion (MIST-B)

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