Tissue Kallikrein Preventing the Restenosis After Stenting of Symptomatic MCA Atherosclerotic Stenosis

Phase 2

• Conditions: Cerebrovascular Disease
• Interventions: Drug: tissue kallikrein

• Registration Number: NCT01558245
• Lead Sponsor: Jinling Hospital, China

Brief Summary

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

Detailed Description

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

Study Timeline

• Study Start: 2011-12
• Study First Submitted: 2011-12-14
• Study First Submitted QC: 2012-03-16
• Study First Posted: 2012-03-20
• Status Verified: 2013-09
• Last Update Submitted: 2013-09-11
• Last Update Posted: 2013-09-12
• Primary Completion: 2013-12
• Study Completion: 2013-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 99

Inclusion Criteria

1. TIA or stroke in the MCA territory refractory to aggressive anti-platelet and regular statin therapy in 3 months
2. Symptomatic MCA M1 segment stenosis ≥ 70% confirmed with DSA
3. Successfully treated with PTAS without acute surgical complications in 12 hours after operation
4. All patients provided fully informed consent

Exclusion Criteria

1. Using angiotensin-converting enzyme inhibitors
2. Severe cardiopulmonary dysfunction, chronic liver disease (A / G inversion, ALT increased 2-fold greater than normal), abnormal renal function (serum creatinine greater than 1.5 times normal)
3. Allergies, the history of allergy to multi-drug
4. The history of cerebral hemorrhage, brain tumors, brain trauma, cerebral embolism and other brain lesions
5. During pregnancy or breast-feeding
6. Not expected to complete follow-up

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Tissue kallikrein group	tissue kallikrein	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.

Primary Outcome Measures

Name	Time	Method
Target lesion failure	12 months	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.

Secondary Outcome Measures

Name	Time	Method
Clinical endpoint	12 months	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.

Trial Locations

Locations (1)

Department of Neurology, Jinling Hospital, Nanjing University School of Medicine; 🇨🇳 Nanjing, Jiangsu, China