Ischemic Stroke, AcutePhase 4MIST-BNCT05512910
Minocycline for Acute Ischemic Stroke Undergoing Endovascular Treatment Due to Basilar Artery Occlusion (MIST-B)
A Phase 4 study testing Minocycline in people with Ischemic Stroke, Acute and Minocycline, run by Xijing Hospital at 1 site in China.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemic Stroke, Acute, Minocycline, Endovascular Treatment
- What is being tested?
- Minocycline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteChina
- Study dates
- 4 Mar 2023to 4 Jun 2025
- Phase
- Phase 4
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 ≥ 5 (Non-Contrast CT or DWI); Pons-midbrain-index of<3.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
Department of Neurology, Xijing Hospital, Fourth Military Medical University
Xi'an, Shaanxi, 710032
About this study
Official 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 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.
- Being tested
- Minocycline
- Keywords
- Ischemic Stroke, Basilar Artery Occlusion, Endovascular Treatment, Minocycline, Neuroprotection, Futile Recanalization
- Medical subject headings
- Ischemic Stroke, cyclopia sequence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MinocyclineDrug
Also called Minocycline hydrochloride
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Minocycline |
| Control group | No intervention | Patients randomized to the control group will receive endovascular treatment and other standard treatment, without minocycline treatment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 24 hours from randomization
Secondary outcomes (20)
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.
Measured: 90 (±14) days from randomization
Good outcome at 90 (±14) days from randomization
An mRS score of 0-3 indicated a good outcome, whereas a score of >3 indicated a poor outcome.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 3 days from randomization
Mortality at 90 (±14) days from randomization
All-cause mortality occurring within 90 (±14) days follow-up were recorded.
Measured: 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.
Measured: 5-7 days from randomization or discharge
Length of Intensive Care Unit (ICU) stay and hospital stay
Length of ICU or hospital stay
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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 %.
Measured: 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.
Measured: 5-7 days from randomization or discharge
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2022
- Study start4 Mar 2023
- Primary completion11 Mar 2025
- Study completion4 Jun 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (28)Papers the sponsor has linked to this study.
- Other trials for Ischemic Stroke, AcuteStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Xijing Hospital
- Sponsor type
- University, hospital or other
- 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
- Responsible party
- Principal investigator, Wen Jiang-3, Xijing Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05512910
- Sponsor's protocol ID
- XJLL-KY20222184
- Acronym
- MIST-B
- Status last verified
- May 2025
- First submitted
- 18 Aug 2022
- Last updated
- 30 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 31662037Emberson 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.
PubMed 25106063Jovin 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.
PubMed 34774198Zhao 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.
PubMed 35387858Hussein 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.
PubMed 20075087Goyal 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.
PubMed 26898852Hill 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.
PubMed 32087818Iadecola 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.
PubMed 21738161Fisher 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.
PubMed 35079135Sun 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.
PubMed 29770166Bai 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.
PubMed 25598025Iadecola 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.
PubMed 32391806De 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.
PubMed 26786115Schafer 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.
PubMed 10799911Koistinaho 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.
PubMed 15674236