Trial Outcomes & Findings for Human Urinary Kallidinogenase Improve Short Term Motor Functional Outcome of Acute Ischemia Stroke Patients (NCT NCT04102956)
NCT ID: NCT04102956
Last Updated: 2021-03-01
Results Overview
The effect of Kallikrein on myelin basic protein (MBP) was determined by comparing the changes of MBP before and after treatment between the Kallikrein+Standard treatment group and the standard treatment group.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
80 participants
Primary outcome timeframe
before (baseline) and after treatment (14 ± 5 days)
Results posted on
2021-03-01
Participant Flow
Participant milestones
| Measure |
Kallikrein+Standard Treatment Group
The Kallikrein+Standard treatment group was given kallikrein through intravenous injection to treatment for 0.15 PNA/day+standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days.
|
Standard Treatment Group
The Standard treatment group was only given standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days.
|
|---|---|---|
|
Overall Study
STARTED
|
42
|
38
|
|
Overall Study
COMPLETED
|
42
|
38
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Kallikrein+Standard Treatment Group
n=42 Participants
The Kallikrein+Standard treatment group was given kallikrein through intravenous injection to treatment for 0.15 PNA/day+standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days.
|
Standard Treatment Group
n=38 Participants
The Standard treatment group was only given standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days.
|
Total
n=80 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
56.762 years
STANDARD_DEVIATION 11.096 • n=42 Participants
|
60.789 years
STANDARD_DEVIATION 9.376 • n=38 Participants
|
58.675 years
STANDARD_DEVIATION 10.4479 • n=80 Participants
|
|
Sex: Female, Male
Female
|
12 Participants
n=42 Participants
|
16 Participants
n=38 Participants
|
28 Participants
n=80 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=42 Participants
|
22 Participants
n=38 Participants
|
52 Participants
n=80 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Hypertension (number, %)
Have hypertension
|
33 Participants
n=42 Participants
|
29 Participants
n=38 Participants
|
62 Participants
n=80 Participants
|
|
Hypertension (number, %)
Without hypertension
|
9 Participants
n=42 Participants
|
9 Participants
n=38 Participants
|
18 Participants
n=80 Participants
|
|
Diabetes (number, %)
Diabetes
|
15 Participants
n=42 Participants
|
13 Participants
n=38 Participants
|
28 Participants
n=80 Participants
|
|
Diabetes (number, %)
Without diabetes
|
27 Participants
n=42 Participants
|
25 Participants
n=38 Participants
|
52 Participants
n=80 Participants
|
|
Coronary heart disease (number, %)
With coronary heart disease
|
3 Participants
n=42 Participants
|
5 Participants
n=38 Participants
|
8 Participants
n=80 Participants
|
|
Coronary heart disease (number, %)
Without coronary heart disease
|
39 Participants
n=42 Participants
|
33 Participants
n=38 Participants
|
72 Participants
n=80 Participants
|
|
Hyperhomocysteinemia (number, %)
Hyperhomocysteinemia
|
18 Participants
n=42 Participants
|
14 Participants
n=38 Participants
|
32 Participants
n=80 Participants
|
|
Hyperhomocysteinemia (number, %)
without hyperhomocysteinemia
|
24 Participants
n=42 Participants
|
24 Participants
n=38 Participants
|
48 Participants
n=80 Participants
|
|
Previous history of cerebral infarction (number, %)
Previous history of cerebral infarction
|
7 Participants
n=42 Participants
|
7 Participants
n=38 Participants
|
14 Participants
n=80 Participants
|
|
Previous history of cerebral infarction (number, %)
Without the history of cerebral infarction
|
35 Participants
n=42 Participants
|
31 Participants
n=38 Participants
|
66 Participants
n=80 Participants
|
|
Smoking and drink (number, %)
Smoking and drink
|
25 Participants
n=42 Participants
|
16 Participants
n=38 Participants
|
41 Participants
n=80 Participants
|
|
Smoking and drink (number, %)
No history of smoking or drinking
|
17 Participants
n=42 Participants
|
22 Participants
n=38 Participants
|
39 Participants
n=80 Participants
|
|
Muscle strength at admission，Median (IQR)
|
2 units on a scale
n=42 Participants
|
2 units on a scale
n=38 Participants
|
2 units on a scale
n=80 Participants
|
|
NIHSS score at admission ( Mean±SD)
|
9.21 units on a scale
STANDARD_DEVIATION 3.258 • n=42 Participants
|
8.05 units on a scale
STANDARD_DEVIATION 3.196 • n=38 Participants
|
8.66 units on a scale
STANDARD_DEVIATION 3.261 • n=80 Participants
|
|
BI index at admission，Median (IQR)
|
25 units on a scale
n=42 Participants
|
25 units on a scale
n=38 Participants
|
25 units on a scale
n=80 Participants
|
|
FA value at admission ( Mean±SD)
|
0.441 units on a scale
STANDARD_DEVIATION 0.055 • n=40 Participants • 78 taken the DTI imaging at admission (40 in the Kallikrein+Standard treatment group and 38 in the Standard treatment group)
|
0.427 units on a scale
STANDARD_DEVIATION 0.044 • n=38 Participants • 78 taken the DTI imaging at admission (40 in the Kallikrein+Standard treatment group and 38 in the Standard treatment group)
|
0.436 units on a scale
STANDARD_DEVIATION 0.484 • n=78 Participants • 78 taken the DTI imaging at admission (40 in the Kallikrein+Standard treatment group and 38 in the Standard treatment group)
|
|
ADC value at admission ( Mean±SD)
|
0.811 m㎡/s
STANDARD_DEVIATION 0.209 • n=40 Participants • Measure Analysis Population Description: 78 taken the DTI imaging at admission (40 in the Kallikrein+Standard treatment group and 38 in the Standard treatment group).
|
0.847 m㎡/s
STANDARD_DEVIATION 0.081 • n=38 Participants • Measure Analysis Population Description: 78 taken the DTI imaging at admission (40 in the Kallikrein+Standard treatment group and 38 in the Standard treatment group).
|
0.831 m㎡/s
STANDARD_DEVIATION 0.162 • n=78 Participants • Measure Analysis Population Description: 78 taken the DTI imaging at admission (40 in the Kallikrein+Standard treatment group and 38 in the Standard treatment group).
|
|
The grade of the severity of corticospinal tract injury ( number, %)
Grade 1
|
6 Participants
n=42 Participants
|
6 Participants
n=38 Participants
|
12 Participants
n=80 Participants
|
|
The grade of the severity of corticospinal tract injury ( number, %)
Grade 2
|
20 Participants
n=42 Participants
|
9 Participants
n=38 Participants
|
29 Participants
n=80 Participants
|
|
The grade of the severity of corticospinal tract injury ( number, %)
Grade 3
|
13 Participants
n=42 Participants
|
16 Participants
n=38 Participants
|
29 Participants
n=80 Participants
|
|
The grade of the severity of corticospinal tract injury ( number, %)
Grade 4
|
3 Participants
n=42 Participants
|
7 Participants
n=38 Participants
|
10 Participants
n=80 Participants
|
|
Intracranial arterial stenosis ( number, %)
Intracranial arterial stenosis
|
20 Participants
n=42 Participants
|
14 Participants
n=38 Participants
|
34 Participants
n=80 Participants
|
|
Intracranial arterial stenosis ( number, %)
Without intracranial arterial stenosis
|
22 Participants
n=42 Participants
|
24 Participants
n=38 Participants
|
46 Participants
n=80 Participants
|
|
VEGF Median (IQR) (pg/ml)
|
22.43 pg/ml
n=33 Participants • Among the enrolled 80 subjects, 59 taken the blood samples (33 in the Kallikrein+Standard treatment group and 26 in the Standard treatment group) to teste the concentrations of VEGF and MBP.
|
22.56 pg/ml
n=26 Participants • Among the enrolled 80 subjects, 59 taken the blood samples (33 in the Kallikrein+Standard treatment group and 26 in the Standard treatment group) to teste the concentrations of VEGF and MBP.
|
22.46 pg/ml
n=59 Participants • Among the enrolled 80 subjects, 59 taken the blood samples (33 in the Kallikrein+Standard treatment group and 26 in the Standard treatment group) to teste the concentrations of VEGF and MBP.
|
|
MBP Median (IQR) (pg/ml)
|
0.42 pg/ml
n=33 Participants • Among the enrolled 80 subjects, 59 taken the blood samples (33 in the Kallikrein+Standard treatment group and 26 in the Standard treatment group) to teste the concentrations of VEGF and MBP.
|
0.64 pg/ml
n=26 Participants • Among the enrolled 80 subjects, 59 taken the blood samples (33 in the Kallikrein+Standard treatment group and 26 in the Standard treatment group) to teste the concentrations of VEGF and MBP.
|
0.56 pg/ml
n=59 Participants • Among the enrolled 80 subjects, 59 taken the blood samples (33 in the Kallikrein+Standard treatment group and 26 in the Standard treatment group) to teste the concentrations of VEGF and MBP.
|
PRIMARY outcome
Timeframe: before (baseline) and after treatment (14 ± 5 days)Population: Among the enrolled 80 subjects, 59 taken the blood samples (33 in the Kallikrein+Standard treatment group and 26 in the Standard treatment group) to test serum myelin basic protein(MBP) and vascular endothelial growth factor (VEGF).
The effect of Kallikrein on myelin basic protein (MBP) was determined by comparing the changes of MBP before and after treatment between the Kallikrein+Standard treatment group and the standard treatment group.
Outcome measures
| Measure |
Kallikrein+Standard Treatment Group
n=33 Participants
The Kallikrein+Standard treatment group was given kallikrein through intravenous injection to treatment for 0.15 PNA/day+standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days.
|
Standard Treatment Group
n=26 Participants
The Standard treatment group was only given standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days.
|
|---|---|---|
|
Myelin Basic Protein (MBP) Comparison Between the Two Groups Before and After Treatment
Prior treatment
|
0.42 pg/ml
Interval 0.23 to 0.8
|
0.64 pg/ml
Interval 0.15 to 1.36
|
|
Myelin Basic Protein (MBP) Comparison Between the Two Groups Before and After Treatment
After treatment
|
0.41 pg/ml
Interval 0.18 to 0.82
|
0.71 pg/ml
Interval 0.27 to 1.35
|
PRIMARY outcome
Timeframe: before (baseline) and after treatment (14 ± 5 days)Population: Among the enrolled 80 subjects, 59 taken the blood samples (33 in the Kallikrein+Standard treatment group and 26 in the Standard treatment group) to test serum myelin basic protein(MBP) and vascular endothelial growth factor (VEGF).
The effect of Kallikrein on vascular endothelial growth factor (VEGF) was judged by comparing the changes of VEGF before and after treatment in the Kallikrein+Standard treatment group and the standard treatment group.
Outcome measures
| Measure |
Kallikrein+Standard Treatment Group
n=33 Participants
The Kallikrein+Standard treatment group was given kallikrein through intravenous injection to treatment for 0.15 PNA/day+standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days.
|
Standard Treatment Group
n=26 Participants
The Standard treatment group was only given standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days.
|
|---|---|---|
|
Comparison of Vascular Endothelial Growth Factor (VEGF) Before and After Treatment Between the Kallikrein+Standard Treatment Group and Standard Treatment Group
Prior treatment
|
22.42 ng/ml
Interval 10.25 to 50.43
|
22.56 ng/ml
Interval 16.06 to 55.24
|
|
Comparison of Vascular Endothelial Growth Factor (VEGF) Before and After Treatment Between the Kallikrein+Standard Treatment Group and Standard Treatment Group
After treatment
|
29.53 ng/ml
Interval 17.31 to 59.68
|
22.91 ng/ml
Interval 9.97 to 47.62
|
PRIMARY outcome
Timeframe: before (baseline) and after treatment (14 ± 5 days)The Barthel Index(BI) is 0 to 100 points. The higher the score, the better the patient's motor function and behavior. The effect of Kallikrein on Barthel Index was judged by comparing the changes of Barthel Index before and after treatment in the Kallikrein+Standard treatment group and the standard treatment group.
Outcome measures
| Measure |
Kallikrein+Standard Treatment Group
n=42 Participants
The Kallikrein+Standard treatment group was given kallikrein through intravenous injection to treatment for 0.15 PNA/day+standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days.
|
Standard Treatment Group
n=38 Participants
The Standard treatment group was only given standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days.
|
|---|---|---|
|
Changes of Barthel Index(BI) Before and After Treatment in the Two Groups
|
17.5 score on a scale
Interval 10.0 to 30.0
|
12.5 score on a scale
Interval 5.0 to 20.0
|
PRIMARY outcome
Timeframe: before (baseline) and after treatment (14 ± 5 days)Using the recording method of grade 6 muscle strength of 0-5 grade, grade 0 means no muscle contraction, grade 5 means normal muscle strength. The effect of Kallikrein on muscle strength was judged by comparing the changes of muscle strength before and after treatment in the Kallikrein+Standard treatment group and the standard treatment group.
Outcome measures
| Measure |
Kallikrein+Standard Treatment Group
n=42 Participants
The Kallikrein+Standard treatment group was given kallikrein through intravenous injection to treatment for 0.15 PNA/day+standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days.
|
Standard Treatment Group
n=38 Participants
The Standard treatment group was only given standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days.
|
|---|---|---|
|
Changes in Muscle Strength of the Kallikrein+Standard Treatment Group and the Standard Treatment Group Before and After Treatment
|
1 score on a scale
Interval 0.0 to 1.0
|
1 score on a scale
Interval 1.0 to 2.0
|
PRIMARY outcome
Timeframe: before (baseline) and after treatment (14 ± 5 days)The NIHSS score is 0 to 42 points. The higher the score, the more severe the nerve damage. The change of NIHSS score is calculated as the value at the earlier time point minus the value at the later time point, that is, the value at the time of admission minus the value after the end of treatment, and then the comparison between groups is performed to obtain the current result.
Outcome measures
| Measure |
Kallikrein+Standard Treatment Group
n=42 Participants
The Kallikrein+Standard treatment group was given kallikrein through intravenous injection to treatment for 0.15 PNA/day+standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days.
|
Standard Treatment Group
n=38 Participants
The Standard treatment group was only given standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days.
|
|---|---|---|
|
Changes of National Institute of Health Stroke Scale(NIHSS) Before and After Treatment in the Two Groups
|
2.88 score on a scale
Standard Deviation 1.35
|
2.16 score on a scale
Standard Deviation 1.59
|
PRIMARY outcome
Timeframe: After 14 ± 5 days of treatmentThe FA value is used to express the anisotropy, which indicates the anisotropic component of water molecules accounts for the total value of diffusion tensor,and ranges from 0 to 1, the closer the value is to 1, the better the fiber bundle integrity. †FA decline rate = (FA contralateral- FA ipsilateral) / FA contralateral， Used to compare the FA decline rate† of the two groups after treatment. A more substantial decrease of FA values is believed to represent the most severely ischemic tissue.
Outcome measures
| Measure |
Kallikrein+Standard Treatment Group
n=40 Participants
The Kallikrein+Standard treatment group was given kallikrein through intravenous injection to treatment for 0.15 PNA/day+standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days.
|
Standard Treatment Group
n=38 Participants
The Standard treatment group was only given standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days.
|
|---|---|---|
|
Change of Fractional Anisotropy Valuev Decline Rate† (FA Decline Rate†)
|
0.036 percentage of decline rate
Interval -0.001 to 0.099
|
0.09 percentage of decline rate
Interval 0.05 to 0.16
|
PRIMARY outcome
Timeframe: After 14 ± 5 days of treatmentThe ADC value of normal brain tissue is in the range of 0.7-0.9×10﹣³m㎡/s. When the brain tissue is acutely affected, it is mostly decreased, and it is mostly increased in subacute or chronic disease. The upper and lower limits of abnormal changes in ADC value are 0.4-2.5×10﹣³m㎡/s. ‡ ADC decline rate = (ADCcontralateral- ADCipsilateral) / ADCcontralateral；Used to compare the ADC decline rate‡ of the two groups after treatment. A more substantial decrease of ADC values is believed to represent the most severely ischemic tissue.
Outcome measures
| Measure |
Kallikrein+Standard Treatment Group
n=40 Participants
The Kallikrein+Standard treatment group was given kallikrein through intravenous injection to treatment for 0.15 PNA/day+standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days.
|
Standard Treatment Group
n=38 Participants
The Standard treatment group was only given standard treatment medicine based on the guidelines for the treatment of acute ischemic stroke for 14 ± 5 days.
|
|---|---|---|
|
Change of Apparent Diffusion Coefficient Value Decline Rate‡（ADC Decline Rate‡）
|
-0.02 percentage of decline rate
Interval -0.06 to 0.01
|
0.03 percentage of decline rate
Interval -0.02 to 0.07
|
Adverse Events
Kallikrein+Standard Treatment Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Standard Treatment Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Xiaoyun Liu PhD
Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Phone: +8613191887318
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place