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

Stroke Clinical Trial

— DREAM-PRIDE  

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04948749
• Other study ID #: HX-A-018(2021)
• Status: Recruiting
• Phase: N/A
• Start date: July 2, 2021
• Est. completion date: July 2025

Study information

• Verified date: January 2024
• Source: Beijing Tiantan Hospital
• Contact: Ning Ma, MD
• Phone: 13581889908
• Email: maning_03[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 792
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Age from 18 to 85 years

2. Patients with ischemic stroke within 30 days of enrolment attributed to 70% to 99% stenosis of a major intracranial artery (internal carotid artery [C4-C7], middle cerebral artery [M1], vertebral artery [V4], or basilar artery) on CTA (According to WASID method)

3. The diameter of the target vessel between 2.0mm - 4.5mm

4. The stenosis lesion length = 14 mm

5. Baseline modified Rankin Scale (mRS) score = 3

6. Patient understands the purpose and requirements of the study, and has provided informed consent

Exclusion Criteria:

1. Ischemic stroke occurred within 7 days before enrolment

2. 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)

3. 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)

4. Unilateral vertebral artery stenosis of 70%-99% with normal contralateral vertebral artery

5. Stroke caused by perforating artery occlusion

6. CT angiographic evidence of severe calcification at target lesion

7. Any history of brain parenchymal or subarachnoid, subdural or extradural haemorrhage in the past 6 weeks

8. 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

9. History of stenting of an intracranial artery

10. Presence of any unequivocal cardiac source of embolism

11. Combined with intracranial tumor, aneurysm or intracranial arteriovenous malformation

12. Cannot tolerate dual antiplatelet therapy

13. Contraindications to heparin, rapamycin, contrast and local or general anesthesia

14. Hemoglobin<100g/L, platelet count <100×109/L

15. Severe hepatic and renal dysfunction

16. INR>1.5 or there are uncorrectable factors leading to bleeding

17. Major surgery within the past 30 days or planned within 90 days

18. Renal artery, iliac artery, and coronary artery requiring simultaneous intervention

19. Life expectancy <1 year

20. Pregnant or lactating women

21. Cannot complete the follow-up due to cognitive, emotional or mental illness

22. Other situations that are not suitable for enrolment according to the judgement of the investigator

23. Enrolment in another study that would conflict with the current study

Related Conditions & MeSH terms

• Intracranial Atherosclerotic Disease
• Stroke

Intervention

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).

Locations

Country	Name	City	State
China	Beijing Tiantan Hospital	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Tiantan Hospital

Country where clinical trial is conducted

China, 

References & Publications (7)

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 J Med. 2011 Sep 15;365(11):993-1003. doi: 10.1056/NEJMoa1105335. Epub 2011 Sep 7. Erratum In: N Engl J Med. 2012 Jul 5;367(1):93. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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 2017. Lancet. 2019 Sep 28;394(10204):1145-1158. doi: 10.1016/S0140-6736(19)30427-1. Epub 2019 Jun 24. Erratum In: Lancet. 2020 Jul 4;396(10243):26. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Primary endpoints are composite event of (1) any stroke or death within 30 days after enrollment, (2) any stroke or death within 30 days after revascularization procedure of the qualifying lesion during follow-up, and (3) ischemic stroke in the territory of the qualifying artery from 31 days to 1 year. Ischemic stroke is defined as a new focal neurological deficit of sudden onset, that is associated with infarction lesion on CT or MRI. Ischemic strokes are classified as in or out of the territory of the symptomatic intracranial artery. Symptomatic brain hemorrhage is defined as parenchymal, subarachnoid, or intraventricular hemorrhage detected by CT or MRI that is associated with new neurological signs or symptoms (headache, change in level of consciousness, focal neurological symptoms) lasting = 24 hours or a seizure.	12 months after enrollment
Primary	Severe or moderate bleeding (GUSTO score)	Bleeding events were defined according to the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) classification for severe or life-threatening, moderate, or mild bleeding: Severe or life-threatening- Either intracranial hemorrhage or bleeding that causes hemodynamic compromise and requires intervention; Moderate- Bleeding that requires blood transfusion but does not result in hemodynamic compromise; Mild- Bleeding that does not meet criteria for either severe/life-threatening or moderate bleeding	12 months after enrollment
Secondary	Residual stenosis after the procedure in DES group	Degree of residual stenosis was measured and calculated according to the methods of the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial.	At the end of the procedure
Secondary	In-stent restenosis (ISR) rate in DES group within 12 months	The ISR is defined as >50% stenosis within or immediately adjacent (within 5 mm) of the implanted stent and >20% absolute luminal loss.	12 months after enrollment
Secondary	Disabling stroke within 1 year	defined as modified Rankin Scale > 3 at 1 year visit	12 months after enrollment
Secondary	Any stroke, death or myocardial infarction within 1 year	Any stroke included ischemic stroke and symptomatic brain hemorrhage. Symptomatic brain hemorrhage refers to parenchymal, subarachnoid, or intraventricular hemorrhage that was associated with a seizure or with symptoms or signs lasting 24 hours or longer.	12 months after enrollment
Secondary	Major non-stroke hemorrhage within 1 year	A major non-stroke-related hemorrhage was defined as any subdural or epidural hemorrhage or a systemic hemorrhage requiring hospitalization, blood transfusion, or surgery.	12 months after enrollment
Secondary	Modified Rankin Scale score at 1 year	The range of modified Rankin Scale was from 0 to 6. 0-No symptoms;1-No significant disability;2-Slight disability;3-Moderate disability;4-Moderately severe disability;5-Severe disability;6 -Dead.A higher score indicates worse a outcome.	12 months after enrollment
Secondary	Death within 1 year	Death within 1 year	12 months after enrollment