Tissue Kallikrein Preventing the Restenosis After Stenting of Symptomatic MCA Atherosclerotic Stenosis
The study aims to determine whether tissue kallikrein (TK) is efficacy for preventing the long-term in-stent restenosis (ISR) after stenting of symptomatic atherosclerotic stenosis of the middle cerebral artery (MCA) M1 segment
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Primary Purpose: Prevention
|Official Title:||Tissue Kallikrein Preventing the Restenosis After Stenting of Symptomatic MCA Atherosclerotic Stenosis|
- Target lesion failure [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]Patients will be evaluated at 1 month, 6 months, and 12 months after the stenting. The primary outcomes are the asymptomatic or symptomatic in-stent restenosis ≥ 50% (affirmed by digital subtraction angiography at 6 and 12 months), new stroke (ischemic and hemorrhagic) or aggravation of the previous ischemic stroke ipsilateral to the severe stenotic artery.
- Clinical endpoint [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]Stroke of other artery territories, myocardial infarction and vascular death will be conducted in-hospital and planned at 1 month, 6 months, and 12 months.
- Laboratory data [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]Laboratory data including bradykinin (BK), TK, platelet inhibitory rate, cGMP, cAMP, hs-CRP, TNF-α, IL-6, LDL-Ch and HDL-Ch will be recorded
|Study Start Date:||December 2011|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: Tissue kallikrein group
Patients in this group will be prescribed with intravenous infusion of TK (0.15 PNAU/d, dissolved in 100ml saline) for 7 days after stenting and then oral administration of pancreatic kallikrein enteric-coated tablet (240U, 3/d) to the end of study. As the foundation treatment, all the enrolled patients will receive aspirin (100 mg/d), clopidogrel (75 mg/d), and atorvastatin (20 mg/d) for the first 6 months and continue with the combination of aspirin and atorvastatin at the previous dosage.
Drug: tissue kallikrein
Human urinary kallidinogenase can transform kininogen to bradykinin (kinin) and vasodilatory factors (kallidin)
Other Name: Human urinary kallidinogenase (HUK)
No Intervention: Control group
Patients in control group will receive foundation treatment, including aspirin (100 mg/d), clopidogrel (75 mg/d), and atorvastatin (20 mg/d) for the first 6 months and continue with the combination of aspirin and atorvastatin at the previous dosage.
A series of studies have confirmed the kallikrein-kinin system (KKS), including kallikrein, kininogen and kinin, plays an important role in the regulation of inflammation secondary to acute and chronic ischemic brain injury. Some researchers found that hTK gene delivery can inhibit the formation of neointimal induced by the common carotid artery ligation in mice. Further study revealed hTK gene transfection in VSMC lead to increased secretion of TK and inhibition of VSMC proliferation. In addition, it was also observed that the serum TK levels were coincident with the carotid artery stenosis. The more severe the stenosis is, the higher the serum TK level is, and the serum TK decreased after carotid artery angioplasty and stent placement. These results suggest that KKS play an important regulatory role in vascular remodeling and TK may exert a beneficial influence in the process of ISR
Please refer to this study by its ClinicalTrials.gov identifier: NCT01558245
|Contact: Renliang Zhang, MD||+ firstname.lastname@example.org|
|Department of Neurology, Jinling Hospital, Nanjing University School of Medicine||Recruiting|
|Nanjing, Jiangsu, China|
|Contact: Renliang Zhang, MD + 86-25-8480386 email@example.com|
|Principal Investigator:||Renliang Zhang, MD||Department of Neurology, Jinling Hospital, Nanjing University School of Medicine|