NCT04102956

Human Urinary Kallidinogenase Improve Short Term Motor Functional Outcome of Acute Ischemia Stroke Patients

Completed Phase 4 Results posted Last updated 1 March 2021

What this trial tests

Phase 4 trial testing Kallikrein in Stroke, Acute in 80 participants. Completed in 25 August 2019.

Timeline

1 July 2017

Primary endpoint
1 March 2019

25 August 2019

Quick facts

Lead sponsor	The Second Hospital of Hebei Medical University
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	80
Start date	1 July 2017
Primary completion	1 March 2019
Estimated completion	25 August 2019
Sites	1 location across China

Drugs / interventions tested

• Kallikrein — full drug profile →

Conditions studied

• Stroke, Acute — all drugs for Stroke, Acute →

Sponsor

The Second Hospital of Hebei Medical University

Who can join

Adults 18 to 80, any sex, with Stroke, Acute. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Myelin Basic Protein (MBP) Comparison Between the Two Groups Before and After Treatment Primary · before (baseline) and after treatment (14 ± 5 days)

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.

Prior treatment

Group	Value	95% CI
Kallikrein+Standard Treatment Group	0.42	0.23 – 0.80
Standard Treatment Group	0.64	0.15 – 1.36

After treatment

Group	Value	95% CI
Kallikrein+Standard Treatment Group	0.41	0.18 – 0.82
Standard Treatment Group	0.71	0.27 – 1.35

Comparison of Vascular Endothelial Growth Factor (VEGF) Before and After Treatment Between the Kallikrein+Standard Treatment Group and Standard Treatment Group Primary · before (baseline) and after treatment (14 ± 5 days)

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.

Prior treatment

Group	Value	95% CI
Kallikrein+Standard Treatment Group	22.42	10.25 – 50.43
Standard Treatment Group	22.56	16.06 – 55.24

After treatment

Group	Value	95% CI
Kallikrein+Standard Treatment Group	29.53	17.31 – 59.68
Standard Treatment Group	22.91	9.97 – 47.62

Changes of Barthel Index(BI) Before and After Treatment in the Two Groups Primary · 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.

Group	Value	95% CI
Kallikrein+Standard Treatment Group	17.5	10 – 30
Standard Treatment Group	12.5	5 – 20

Changes in Muscle Strength of the Kallikrein+Standard Treatment Group and the Standard Treatment Group Before and After Treatment Primary · 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.

Group	Value	95% CI
Kallikrein+Standard Treatment Group	1	0 – 1
Standard Treatment Group	1	1 – 2

Changes of National Institute of Health Stroke Scale(NIHSS) Before and After Treatment in the Two Groups Primary · 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.

Group	Value	95% CI
Kallikrein+Standard Treatment Group	2.88	± 1.35
Standard Treatment Group	2.16	± 1.59

Change of Fractional Anisotropy Valuev Decline Rate† (FA Decline Rate†) Primary · After 14 ± 5 days of treatment

The 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.

Group	Value	95% CI
Kallikrein+Standard Treatment Group	0.036	-0.001 – 0.099
Standard Treatment Group	0.09	0.05 – 0.16

Change of Apparent Diffusion Coefficient Value Decline Rate‡（ADC Decline Rate‡） Primary · After 14 ± 5 days of treatment

The 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.

Group	Value	95% CI
Kallikrein+Standard Treatment Group	-0.02	-0.06 – 0.01
Standard Treatment Group	0.03	-0.02 – 0.07

Sponsor's own description

Acute cerebral infarction is a common type of ischemic stroke, causing brain dysfunction in patients with high morbidity and disability. With the changes in people's diet, lifestyle patterns and population aging, the incidence of acute cerebral infarction has increased year by year, which has become an important cause of disability and death in middle-aged and elderly patients. 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 AIS has not been systematically investigated. This study aimed to assess the effect of HUK on motor functional outcome and relative corticospinal tract recovery in the patients with AIS. Diffusion tensor imaging(DTI) and diffusion tensor tractography(DTT) have all been used to observe features of cerebral white matter fibrous structures. In addition, diffusion tensor tractography which is used to trace fiber bundle and evaluate white matter fiber bundle integrity and direction is the only non-invasive imaging method to display the corticospinal tract in vivo.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Protective effects of human urinary kallidinogenase against corticospinal tract damage in acute ischemic stroke patients.
   Li P, Lu H, Shi X, Yan J, et al · · 2024 · cited 3× · PMID 38526971 · DOI 10.1097/wnr.0000000000002028