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

Jinling Hospital, China

Status and phase: Unknown; Phase 2

Conditions: Cerebrovascular Disease

Treatments: Drug: tissue kallikrein

Study type: Interventional

Funder types: Other

Identifiers

NCT01558245

KPRASS

Details and patient eligibility

About

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

Full 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

Enrollment: 99 estimated patients

Sex: All

Ages: 30+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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99 participants in 2 patient groups

Tissue kallikrein group

Experimental group

Description:

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.

Treatment:

Drug: tissue kallikrein

Control group

No Intervention group

Description:

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.