Human Urinary Kallidinogenase Improve Short Term Motor Functional Outcome by Reducing the Corticospinal Tract Damage in Acute Ischemia Stroke Patients
Phase: PHASE4
Conditions: Stroke, Acute
Sponsor: The Second Hospital of Hebei Medical University

Human Urinary Kallidinogenase Improve Short Term Motor
Functional Outcome By Reducing The Corticospinal Tract
Damage In Acute Ischemia Stroke Patients
Central Contact Person:Peifang Li
Telephone:
+8615203216570
Department ：Department of Neurology
Responsible institution：The Second Hospital of Hebei Medical
University
Date：2019.07.15

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Study Protocol

Project name: Human urinary kallidinogenase improve short term motor
functional outcome by reducing the corticospinal tract damage in acute ischemia
stroke patients

Background and Purpose: The human urinary kallidinogenase (HUK) was used
in China in the management of acute ischemic stroke(AIS) in recent years.
However, the mechanism of HUK on the treatment of AIS has not been
systematically investigated. This study aimed to assess the effect of HUK on
motor functional outcome and relative corticospinal tract damage recovery in the
patients with AIS.

The research participants：The AIS patients in the Neurology Department of the
Second Hospital of Hebei Medical University, North China, from July 2017 to
March 2019 were eligible for inclusion according to the inclusion criteria below,
The acute ischemic stroke diagnosis conformed to "Guidelines for the Diagnosis
and Treatment of Acute Ischemic Stroke in China 2014". This study was
approved by the Ethics Committee of the Second Hospital of Hebei Medical
University (2018-P023).
Inclusion and exclusion criteria
Inclusion Criteria: (1) The enrollment age was between 18 and 80 years old; (2)
Within 72 hours of onset; (3) Diagnosed as acute ischemic stroke, and confirmed
by MRI as an acute infarct with the unilateral corticospinal tract damage; (4) The
patients’ muscle strength of paralyzed side at the admission was below or equal
to grade 4; (5) No history of cerebral infarction, or with cerebral infarction
history but without residual physical activity disorder; (6) No other intracranial

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lesions; (7) The patients or their surrogates voluntarily sign the informed
consent.
Exclusion Criteria:
(1) Intracranial hemorrhagic disease include cerebral
hemorrhage, subarachnoid hemorrhage, etc; (2) Transient ischemic attack; (3)
Intravenous thrombolysis and interventional thrombectomy; (4) Serious physical
illness affects limb movement before enrollment; (5) Apply other neurotrophic
and promote nerve regeneration drugs through the trial; (6) Unstable vital signs,
severe liver and kidney diseases or malignant tumors; (7) Inability to understand
and/or comply with the study procedures and/or follow-up due to mental
disorders or emotional disorders.

Therapy：With the random number table method, the patients were consecutively
enrolled and divided into two groups: the HUK group and the control group. All
patients were treated with standard therapy based on the Guideline, besides, the
HUK group were given the HUK (Guangdong tianpu biochemical pharmaceutical
co. LTD, National drug approval no. H20052065) for injection (0.15PNA diluted
in 100ml physiological sodium chloride solution, 1 time/day, intravenous infusion)
within 24 hours after admission. Both groups were treated continuously for 14 ±
5 days.

Data collection：At admission and discharge, 2-3ml venous blood was collected,
blood samples were centrifuged and serum were collected, the concentrations of
VEGF and MBP were tested by ELISA (Wuhan Servicebio Technology Co., Ltd).
At the same time, National Institute of Health Stroke Scale(NIHSS), Barthel

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Index(BI), muscle strength were also assessed. Both groups underwent a brain
MRI within 72h of onset and 14±5 days after treatment. The sequences included
the axial and sagittal T2WI sequence (TR/TE, 5000/89 ms), the axial T1WI
sequence (TR/TE, 500/8.4 ms), and the axial T2 FLAIR (Fluid-attenuated
Inversion-recovery) sequence (TR/TE/TI, 9000/89ms), axial DWI sequence. The
diffusion tensor imaging (DTI) examination adopted single excitation SE-EPI
sequence, TR/TE: 3138/60 ms. DTI were performed to record the Dffusion
Tensor
Tractography(DTT)
classification,
Fractional
anisotrophy(FA)
and
Apparent Diffusion Coefficient(ADC) parameters were to evaluate the injury
degree of the corticospinal tract; The decline rate (the decline rate = [contralateral
side - ipsilateral side ] / contralateral side) was obtained, ΔFA and ΔADC
represent the decline rate of the second time minus the first time. The severity of
the corticospinal tract injury evaluated by DTT was classified as: Grade 1, with
complete corticospinal tract; Grade 2, the corticospinal tract was slightly injured
with the injury less than 50%. Grade 3, moderate corticospinal tract injury with
the injury between 50%~75%; Grade 4, severe corticospinal tract injury, almost
interrupted more than 75%. Besides, the Magnetic resonance angiography(MRA)
was also performed, for persons with intracranial arteries≥70% were diagnosed
as severe stenosis.
Primary outcome is the short-term motor function prognosis of the AIS patients in
two groups, secondary outcomes are the recovery of corticospinal tract and the
serum MBP and VEGF changes during treatment.