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

NCT ID: NCT01558245

Last Updated: 2013-09-12

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 99 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-12-31
• Study Completion Date: 2013-12-31

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

Conditions

Cerebrovascular Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

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.

Group Type: EXPERIMENTAL

tissue kallikrein

Intervention Type: DRUG

Human urinary kallidinogenase can transform kininogen to bradykinin (kinin) and vasodilatory factors (kallidin)

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

tissue kallikrein

Human urinary kallidinogenase can transform kininogen to bradykinin (kinin) and vasodilatory factors (kallidin)

Intervention Type: DRUG

Other Intervention Names

Human urinary kallidinogenase (HUK)

Eligibility Criteria

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

• Minimum Eligible Age: 30 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jinling Hospital, China

OTHER

Sponsor Role: lead

Responsible Party

Zhang Renliang

Clinical Professor and Associate Director of Department of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Renliang Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Neurology, Jinling Hospital, Nanjing University School of Medicine

Locations

Department of Neurology, Jinling Hospital, Nanjing University School of Medicine

Nanjing, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Renliang Zhang, MD

Role: CONTACT

zhangrenliang@gmail.com

+ 86-25-8480386

Facility Contacts

Renliang Zhang, MD

Role: primary

zhangrenliang@gmail.com

+ 86-25-8480386

References

Shi R, Zhang R, Yang F, Lin M, Li M, Liu L, Yin Q, Lin H, Xiong Y, Liu W, Fan X, Dai Q, Zhou L, Lan W, Cao Q, Chen X, Xu G, Liu X. Tissue Kallikrein Prevents Restenosis After Stenting of Severe Atherosclerotic Stenosis of the Middle Cerebral Artery: A Randomized Controlled Trial. Medicine (Baltimore). 2016 Feb;95(6):e2809. doi: 10.1097/MD.0000000000002809.

Reference Type: DERIVED

PMID: 26871851 (View on PubMed)

Lan W, Yang F, Liu L, Yin Q, Li M, Li Z, Sang H, Xu G, Ma M, Zhang Z, Liu Z, Liu X, Zhang R. Tissue kallikrein preventing the restenosis after stenting of symptomatic MCA atherosclerotic stenosis (KPRASS). Int J Stroke. 2014 Jun;9(4):533-5. doi: 10.1111/ijs.12229. Epub 2013 Dec 20.

Reference Type: DERIVED

PMID: 24354519 (View on PubMed)

Other Identifiers

KPRASS

Identifier Type: -

Identifier Source: org_study_id