Drug Eluting Stenting and Aggressive Medical Treatment for Preventing Recurrent Stroke in Intracranial Atherosclerotic Disease Trial

Official title

Drug Eluting Stenting and Aggressive Medical Treatment for Preventing Recurrent Stroke in Intracranial Atherosclerotic Disease Trial: a Prospective, Randomized, Open-labelled, Blinded End-point Trial (DREAM-PRIDE)

Overview

The aim of DREAM-PRIDE is to evaluate whether implantation of drug-eluting stent (DES) combined with aggressive medical treatment is more efficacious in prevention of 1-year stroke recurrence than standard medical treatment alone for symptomatic intracranial atherosclerotic disease.

Detailed description

This trial is a prospective, multi-center, 1:1 randomized using drug-eluting (Sirolimus) stent combined with aggressive medical treatment versus standard medical treatment to treat symptomatic intracranial atherosclerotic disease. Primary efficacy endpoints (any of the following): 1) any stroke or death within 30 days after enrollment, 2) any stroke or death within 30 days after a revascularization procedure of the qualifying lesion during follow-up, 3) ischemic stroke in the territory of the qualifying artery beyond 30 days to 1 year.

Interventions

• Device Drug Eluting Stent implantation
  The Maurora ® Sirolimus Eluting Stent System for intracranial PTA treatment comprises of a balloon expandable sirolimus eluting stent and a delivery catheter that features a rapid exchange catheter design with a semi-compliant balloon located at its distal end.
• Drug Aggressive medical treatment
  Aggressive medical treatment consists of dual antiplatelet treatment (aspirin 100 mg per day for the entire follow-up, clopidogrel 75 per day mg, or ticagrelor 90 mg twice per day for 6 months after enrollment).
• Behavioral Risk factor management
  Management of risk factors (hypertension, diabetes, lipoprotein metabolism disorder, smoking and exercise)
• Drug Standard medical treatment
  Standard medical treatment consists of dual antiplatelet treatment (aspirin 100 mg per day for the entire follow-up, clopidogrel 75 per day mg, or ticagrelor 90 mg twice per day for 3 months after enrollment).

Primary outcome measures

• Any stroke or death within 30 days of enrollment or any revascularization procedure OR an ischemic stroke in the territory of the symptomatic intracranial artery between 31 day to 1 year. [Time frame: 12 months after enrollment]
• Severe or moderate bleeding (GUSTO score) [Time frame: 12 months after enrollment]

Secondary outcome measures (8)

• Residual stenosis after the procedure in DES group [Time frame: At the end of the procedure]
• In-stent restenosis (ISR) rate in DES group within 12 months [Time frame: 12 months after enrollment]
• Disabling stroke within 1 year [Time frame: 12 months after enrollment]
• Any stroke, death or myocardial infarction within 1 year [Time frame: 12 months after enrollment]
• Major non-stroke hemorrhage within 1 year [Time frame: 12 months after enrollment]
• Modified Rankin Scale score at 1 year [Time frame: 12 months after enrollment]
• Symptomatic intracranial hemorrhage within 1 year [Time frame: 12 months after enrollment]
• Death within 1 year [Time frame: 12 months after enrollment]

Eligibility criteria

Inclusion criteria

• Age from 18 to 85 years
• Patients with ischemic stroke within 30 days of enrolment attributed to 70% to 99% stenosis of a major intracranial artery (internal carotid artery \[C5-C7\], middle cerebral artery \[M1\], vertebral artery \[V4\], or basilar artery) on CTA (According to WASID method)
• The diameter of the target vessel between 2.0mm - 4.5mm
• The stenosis lesion length ≤ 14 mm
• Baseline modified Rankin Scale (mRS) score ≤ 3
• Patient understands the purpose and requirements of the study, and has provided informed consent

Exclusion criteria

• Ischemic stroke occurred within 7 days before enrolment
• Tandem extracranial or intracranial stenosis (70%-99%) or occlusion that is proximal or distal to the target intracranial lesion (NOTE: an exception is allowed if stenosis or occlusion involves a single vertebral artery proximal to a symptomatic basilar artery stenosis and the contralateral vertebral artery is supplying the basilar artery)
• Bilateral intracranial vertebral artery stenosis of 70%-99% and uncertainty about which artery is symptomatic (NOTE: an exception is that if bilateral vertebral arteries with 70%-99% stenosis but unequal in size, the dominant side is considered as symptomatic)
• Unilateral vertebral artery stenosis of 70%-99% with normal contralateral vertebral artery
• Stroke caused by perforating artery occlusion
• CT angiographic evidence of severe calcification at target lesion
• Any history of brain parenchymal or subarachnoid, subdural or extradural haemorrhage in the past 6 weeks
• Intracranial artery stenosis caused by non-atherosclerotic lesions, including: arterial dissection, Moyamoya disease, vasculitis disease, herpes zoster, varicella-zoster or other viral vascular diseases, neurosyphilis, any other intracranial infections, any intracranial stenosis related to cerebrospinal fluid cells, radiation-induced vascular disease, fibromuscular dysplasia, sickle cell disease, neurofibromatosis, central nervous system benign vascular disease, postpartum vascular disease, suspected vasospasm, suspicious embolism recanalization, etc
• History of stenting of an intracranial artery
• Presence of any unequivocal cardiac source of embolism
• Combined with intracranial tumor, aneurysm or intracranial arteriovenous malformation
• Cannot tolerate dual antiplatelet therapy
• Contraindications to heparin, rapamycin, contrast and local or general anesthesia
• Hemoglobin<100g/L, platelet count <100×109/L
• Severe hepatic and renal dysfunction
• INR>1.5 or there are uncorrectable factors leading to bleeding
• Major surgery within the past 30 days or planned within 90 days
• Renal artery, iliac artery, and coronary artery requiring simultaneous intervention
• Life expectancy <1 year
• Pregnant or lactating women
• Cannot complete the follow-up due to cognitive, emotional or mental illness
• Other situations that are not suitable for enrolment according to the judgement of the investigator
• Enrolment in another study that would conflict with the current study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

China · 18 centers

• Beijing Tiantan Hospital — Beijing
• Beijing Daxing District People's Hospital — Beijing
• Hejian People's Hospital — Cangzhou
• North China University of Science and Technology Affiliated Hospital — Tangshan
• Xingtai City Third Hospital — Xingtai
• General Hospital of The Yangtze River Shipping — Wuhan
• Baotou Central Hospital — Baotou
• Inner Mongolia Autonomous Region People's Hospital — Hohhot
• … and 10 more centers

Publications

• Zhou M, Wang H, Zeng X, Yin P, Zhu J, Chen W, Li X, Wang L, Wang L, Liu Y, Liu J, Zhang M, Qi J, Yu S, Afshin A, Gakidou E, Glenn S, Krish VS, Miller-Petrie MK, Mountjoy-Venning WC, Mullany EC, Redford SB, Liu H, Naghavi M, Hay SI, Wang L, Murray CJL, Liang X. Mortality, morbidity, and risk factors in China and its provinces, 1990-2017: a systematic analysis for the Global Burden of Disease Study PMID 31248666
• GBD 2016 Stroke Collaborators. Global, regional, and national burden of stroke, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019 May;18(5):439-458. doi: 10.1016/S1474-4422(19)30034-1. Epub 2019 Mar 11. PMID 30871944
• Chimowitz MI, Lynn MJ, Howlett-Smith H, Stern BJ, Hertzberg VS, Frankel MR, Levine SR, Chaturvedi S, Kasner SE, Benesch CG, Sila CA, Jovin TG, Romano JG; Warfarin-Aspirin Symptomatic Intracranial Disease Trial Investigators. Comparison of warfarin and aspirin for symptomatic intracranial arterial stenosis. N Engl J Med. 2005 Mar 31;352(13):1305-16. doi: 10.1056/NEJMoa043033. PMID 15800226
• Chimowitz MI, Lynn MJ, Derdeyn CP, Turan TN, Fiorella D, Lane BF, Janis LS, Lutsep HL, Barnwell SL, Waters MF, Hoh BL, Hourihane JM, Levy EI, Alexandrov AV, Harrigan MR, Chiu D, Klucznik RP, Clark JM, McDougall CG, Johnson MD, Pride GL Jr, Torbey MT, Zaidat OO, Rumboldt Z, Cloft HJ; SAMMPRIS Trial Investigators. Stenting versus aggressive medical therapy for intracranial arterial stenosis. N Engl PMID 21899409
• Shin YS, Kim BM, Suh SH, Jeon P, Kim DJ, Kim DI, Kim BS, Kim KH, Heo JH, Nam HS, Kim YD. Wingspan stenting for intracranial atherosclerotic stenosis: clinical outcomes and risk factors for in-stent restenosis. Neurosurgery. 2013 Apr;72(4):596-604; discussion 604. doi: 10.1227/NEU.0b013e3182846e09. PMID 23277374
• Jin M, Fu X, Wei Y, Du B, Xu XT, Jiang WJ. Higher risk of recurrent ischemic events in patients with intracranial in-stent restenosis. Stroke. 2013 Nov;44(11):2990-4. doi: 10.1161/STROKEAHA.113.001824. Epub 2013 Aug 20. PMID 23963335
• Lu WD, Huang CW, Li YH, Chen JY. Multiple Mechanisms in 1 In-Stent Restenosis Assessed by Optical Coherence Tomography. JACC Cardiovasc Interv. 2017 Nov 27;10(22):2340-2341. doi: 10.1016/j.jcin.2017.07.017. Epub 2017 Nov 1. No abstract available. PMID 29102578

Identifiers

NCT: NCT04948749 · HX-A-018(2021)

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗