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

Primary Purpose

Cerebrovascular Disease

Status

Unknown status

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

tissue kallikrein

Sponsored by

Jinling Hospital, China

About this trial

This is an interventional prevention trial for Cerebrovascular Disease focused on measuring ischemic stroke; in-stent restenosis; tissue kallikrein;, the middle cerebral artery; atherosclerotic stenosis

Eligibility Criteria

30 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

Using angiotensin-converting enzyme inhibitors
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)
Allergies, the history of allergy to multi-drug
The history of cerebral hemorrhage, brain tumors, brain trauma, cerebral embolism and other brain lesions
During pregnancy or breast-feeding
Not expected to complete follow-up

Sites / Locations

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Tissue kallikrein group

Control group

Arm 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.

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.

Outcomes

Primary Outcome Measures

Target lesion failure

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

Clinical endpoint

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.

Full Information

NCT ID

First Posted

December 14, 2011

Last Updated

September 11, 2013

Sponsor

Jinling Hospital, China

1. Study Identification

Unique Protocol Identification Number

NCT01558245

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2013

Overall Recruitment Status

Unknown status

Study Start Date

December 2011 (undefined)

Primary Completion Date

December 2013 (Anticipated)

Study Completion Date

December 2013 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Jinling Hospital, China

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Cerebrovascular Disease

Keywords

ischemic stroke; in-stent restenosis; tissue kallikrein;, the middle cerebral artery; atherosclerotic stenosis

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

Investigator

Allocation

Randomized

Enrollment

99 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Tissue kallikrein group

Arm Type

Experimental

Arm 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.

Arm Title

Control group

Arm Type

No Intervention

Arm 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.

Intervention Type

Drug

Intervention Name(s)

tissue kallikrein

Other Intervention Name(s)

Human urinary kallidinogenase (HUK)

Intervention Description

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

Primary Outcome Measure Information:

Title

Target lesion failure

Description

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.

Time Frame

12 months

Secondary Outcome Measure Information:

Title

Clinical endpoint

Description

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.

Time Frame

12 months

Other Pre-specified Outcome Measures:

Title

Laboratory data

Description

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

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion Criteria: TIA or stroke in the MCA territory refractory to aggressive anti-platelet and regular statin therapy in 3 months Symptomatic MCA M1 segment stenosis ≥ 70% confirmed with DSA Successfully treated with PTAS without acute surgical complications in 12 hours after operation All patients provided fully informed consent Exclusion Criteria: Using angiotensin-converting enzyme inhibitors 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) Allergies, the history of allergy to multi-drug The history of cerebral hemorrhage, brain tumors, brain trauma, cerebral embolism and other brain lesions During pregnancy or breast-feeding Not expected to complete follow-up

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Renliang Zhang, MD

Phone

+ 86-25-8480386

Email

zhangrenliang@gmail.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Renliang Zhang, MD

Organizational Affiliation

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

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Nanjing

State/Province

Jiangsu

Country

China

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Renliang Zhang, MD

Phone

+ 86-25-8480386

Email

zhangrenliang@gmail.com

12. IPD Sharing Statement

Citations:

PubMed Identifier

26871851

Citation

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.

Results Reference

derived

PubMed Identifier

24354519

Citation

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.

Results Reference

derived

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

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