Acute Ischemic StrokeKREATENCT07483281
Efficacy and Safety of Human Urinary Kallidinogenase Combined With Reteplase Intravenous Thrombolysis in the Treatment of Acute Ischemic Stroke
A study testing Human Urinary Kallidinogenase and Clinical Routine Treatment in people with Acute Ischemic Stroke, run by China-Japan Union Hospital at 1 site in China.
Trial summary
This study is a multicentre, randomized, blinded-endpoint trial that aims to evaluate the efficacy and safety of human urinary kallidinogenase combined with reteplase intravenous thrombolysis in the treatment of acute ischemic stroke Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Ischemic Stroke
- What is being tested?
- Human Urinary Kallidinogenase and Clinical Routine Treatment
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 220 participants
- Where
- 1 siteChina
- Study dates
- 1 May 2026to 18 Jun 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Meet the diagnostic criteria of the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2023
- Age ≥ 18 years
- The time from last known well to treatment is within 4.5 hours
- First-ever ischemic stroke or have history of ischemic stroke but mRS≤1 before onset
- 6 ≤NIHSS≤ 16
- Meet the clinical thrombolysis indications in the Chinese Guidelines for the Diagnosis and Treatment of Ischemic Stroke and receive reteplase intravenous thrombolysis
- Have provided signed written informed consent from the patient or the patient's legal representative
Who cannot join
- Preoperative non-contrast head CT shows Alberta Stroke Program Early CT Score (ASPECTS) ≤ 6
- Presence of contraindications to intravenous thrombolysis
- Patients who have been on angiotensin-converting enzyme inhibitor (ACEI) drugs and within 5 half-lives (according to the specific drug instructions) before initiate Human Urinary Kallidinogenase treatment
- Planed for endovascular treatment
- Patients with fracture, claudication and other factors affecting functional outcome score upon admission
- Use of Edaravone Injection, Edaravone Dexborneol Injection, Sublingual Edaravone Dexborneol, Butylphthalide Injection or Capsules after the onset of the current episode
Show all 17Show fewer
- Severe uncontrolled hypertension: systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg
- History of severe food or drug allergies, or prior allergy or intolerance to urinary kallidinogenase for injection
- Pregnant or lactating women, or patients planning pregnancy within 90 days
- Renal failure or severe renal impairment (creatinine clearance < 30 mL/min) at screening
- Liver function impairment: Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times the upper limit of normal, or liver diseases (e.g., acute/chronic hepatitis, cirrhosis)
- Heart failure (NYHA Class III or IV), unstable angina, acute myocardial infarction, severe arrhythmia, or second/third-degree cardiac conduction obstruction within 6 months before randomization
- Drug abuse or addiction in the past year
- Concurrent malignant tumors or severe systemic diseases with an expected survival < 90 days
- Severe mental disorders or dementia unable to complete the informed consent and follow-up
- Participation in any interventional drug or device clinical trial within 3 months before screening
- Patients deemed unsuitable for the study by the investigator
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
China-Japan Union Hospital of Jilin University
Changchun, Jilin, 130033
Guangxian Nan, +86 13404320500, nangx@jlu.edu.cn
Guangxian Nan, MD, Ph.D
About this study
This study is a multicentre, randomized, blinded-endpoint trial that aims to evaluate the efficacy and safety of human urinary kallidinogenase combined with reteplase intravenous thrombolysis in the treatment of acute ischemic stroke
Read the detailed description
Reteplase intravenous thrombolysis for acute ischemic stroke (AIS) owing to a prolonged half-life and bolus dosing. However, some patients still do not achieve favorable outcomes, likely due to complex pathophysiological processes such as oxidative stress, inflammation, and apoptosis triggered after stroke. Human urinary kallidinogenase primarily acts through the kallikrein-kinin system (KKS). It can improve oxygen supply to ischemic brain tissue, promote the establishment of collateral circulation, alleviate ischemic reperfusion injury, and exert anti-inflammatory and antioxidant effects. Whether its combination with reteplase can further improve neurological recovery in patients without increasing the risk of hemorrhage remains unreported. Therefore, this study aims to investigate the efficacy and safety of combining human urinary kallidinogenase with reteplase in the treatment of AIS.
- Conditions
- Acute Ischemic Stroke
- Being tested
- Human Urinary Kallidinogenase, Clinical Routine Treatment
- Keywords
- Acute Ischemic Stroke, Human Urinary Kallidinogenase, KLK, Reteplase, HUK, Intravenous Thrombolysis
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human Urinary KallidinogenaseDrug
Also called KLK, HUK
Intravenous injections of urinary kallidinogenase (0.15 PNA units) dissolved in 100 ml of normal saline, administered via slow intravenous drip over no less than 50 minutes,once a day. The solvent can be increased and/or slowed down according to the patient's condition for 8±1 days
Clinical Routine TreatmentOther
Conventional therapy of acute ischemic stroke after based on Chinese guidelines
| Study group | Role | What they receive |
|---|---|---|
| Intervention group:Human Urinary Kallidinogenase + Clinical Routine Treatment | Experimental | Intravenous injections of Human urinary kallidinogenase (0.15 PNA units) dissolved in 100 ml of normal saline once a day for 8±1 days Receives: Drug: Human Urinary Kallidinogenase |
| Control group: Clinical Routine Treatment | Other | Conventional therapy of acute ischemic stroke after based on Chinese guidelines Receives: Other: Clinical Routine Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with modified Rankin Scale (mRS) 0-1
mRS scores range from 0 to 6. 0=no symptoms,1 = symptoms without clinically significant disability,2 = slight disability,3 = moderate disability,4 = moderately severe disability,5 = severe disability; and 6 = death
Measured: 90 days
Secondary outcomes (8)
ordinal distribution of modified Rankin Scale (mRS)
The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome
Measured: 90 days
Proportion of patients with modified Rankin Scale (mRS) 0-2
The minimum and maximum values of mRS are 0 and 6, respectively; higher score mean a worse outcome
Measured: 90 days
occurrence of early neurological improvement (ENI)
ENI is defined as more than 4-point decrease in National Institute of Health stroke scale score or NIHSS score ≤ 1
Measured: 24 、24-48 hours
change of National Institute of Health stroke scale (NIHSS) score
NIHSS ranges from 0 to 42, a low value represents a better outcome
Measured: 24 、24-48 hours
change in National Institute of Health stroke scale (NIHSS) score
NIHSS ranges from 0 to 42, a low value represents a better outcome
Measured: 8±1 days
Changes of Barthel index from baseline
Barthel Index is used to assess patients' activities of daily living (ADL), with a total score of 100 points. A higher score indicates better self-care ability
Measured: 90 days
Proportion of patients with Barthel Index (BI) ≥ 95
Barthel Index is used to assess patients' activities of daily living (ADL), with a total score of 100 points. A higher score indicates better self-care ability
Measured: 90 days
Stroke recurrence rate
Stroke recurrence rate within 90 days
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2026
- Study start1 May 2026 (estimated)
- Primary completion1 Mar 2028 (estimated)
- Study completion18 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Ischemic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- China-Japan Union Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Guangxian Nan, China-Japan Union Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07483281
- Sponsor's protocol ID
- KLK-S029
- Acronym
- KREATE
- Status last verified
- Mar 2026
- First submitted
- 16 Mar 2026
- Last updated
- 30 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Human Urinary Kallidinogenase Combined With Reteplase Intravenous Thrombolysis in the Treatment of Acute Ischemic Stroke
- ClinicalTrials.gov ID
- NCT07483281
- Acronym / sponsor ID
- KREATE / KLK-S029
- Conditions
- Acute Ischemic Stroke
- Keywords
- Acute Ischemic Stroke, Human Urinary Kallidinogenase, KLK, Reteplase, HUK, Intravenous Thrombolysis
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- China-Japan Union HospitalUniversity, hospital or other
- Study start
- 1 May 2026 (estimated)
- Primary completion
- 1 Mar 2028 (estimated)
- Study completion
- 18 Jun 2028 (estimated)
- First posted
- 19 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a multicentre, randomized, blinded-endpoint trial that aims to evaluate the efficacy and safety of human urinary kallidinogenase combined with reteplase intravenous thrombolysis in the treatment of acute ischemic stroke
Detailed description
Reteplase intravenous thrombolysis for acute ischemic stroke (AIS) owing to a prolonged half-life and bolus dosing. However, some patients still do not achieve favorable outcomes, likely due to complex pathophysiological processes such as oxidative stress, inflammation, and apoptosis triggered after stroke. Human urinary kallidinogenase primarily acts through the kallikrein-kinin system (KKS). It can improve oxygen supply to ischemic brain tissue, promote the establishment of collateral circulation, alleviate ischemic reperfusion injury, and exert anti-inflammatory and antioxidant effects. Whether its combination with reteplase can further improve neurological recovery in patients without increasing the risk of hemorrhage remains unreported. Therefore, this study aims to investigate the efficacy and safety of combining human urinary kallidinogenase with reteplase in the treatment of AIS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention group:Human Urinary Kallidinogenase + Clinical Routine Treatment | Experimental | Drug: Human Urinary KallidinogenaseIntravenous injections of Human urinary kallidinogenase (0.15 PNA units) dissolved in 100 ml of normal saline once a day for 8±1 days |
| Control group: Clinical Routine Treatment | Other | Other: Clinical Routine TreatmentConventional therapy of acute ischemic stroke after based on Chinese guidelines |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Meet the diagnostic criteria of the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2023
- Age ≥ 18 years
- The time from last known well to treatment is within 4.5 hours
- First-ever ischemic stroke or have history of ischemic stroke but mRS≤1 before onset
- 6 ≤NIHSS≤ 16
Key exclusion criteria (17 listed)
- Preoperative non-contrast head CT shows Alberta Stroke Program Early CT Score (ASPECTS) ≤ 6
- Presence of contraindications to intravenous thrombolysis
- Patients who have been on angiotensin-converting enzyme inhibitor (ACEI) drugs and within 5 half-lives (according to the specific drug instructions) before initiate Human Urinary Kallidinogenase treatment
- Planed for endovascular treatment
- Patients with fracture, claudication and other factors affecting functional outcome score upon admission
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Human Urinary KallidinogenaseAlso: KLK, HUKIntravenous injections of urinary kallidinogenase (0.15 PNA units) dissolved in 100 ml of normal saline, administered via slow intravenous drip over no less than 50 minutes,once a day. The solvent can be increased and/or slowed down according to the patient's condition for 8±1 days | Drug | Intervention group:Human Urinary Kallidinogenase + Clinical Routine Treatment |
| Clinical Routine TreatmentConventional therapy of acute ischemic stroke after based on Chinese guidelines | Other | Control group: Clinical Routine Treatment |
Primary outcome
Proportion of patients with modified Rankin Scale (mRS) 0-1
Time frame: 90 days
mRS scores range from 0 to 6. 0=no symptoms,1 = symptoms without clinically significant disability,2 = slight disability,3 = moderate disability,4 = moderately severe disability,5 = severe disability; and 6 = death
8 secondary outcomes
ordinal distribution of modified Rankin Scale (mRS)
Time frame: 90 days
Proportion of patients with modified Rankin Scale (mRS) 0-2
Time frame: 90 days
occurrence of early neurological improvement (ENI)
Time frame: 24 、24-48 hours
change of National Institute of Health stroke scale (NIHSS) score
Time frame: 24 、24-48 hours
change in National Institute of Health stroke scale (NIHSS) score
Time frame: 8±1 days
Changes of Barthel index from baseline
Time frame: 90 days
Proportion of patients with Barthel Index (BI) ≥ 95
Time frame: 90 days
Stroke recurrence rate
Time frame: 90 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Human Urinary Kallidinogenase and Clinical Routine Treatment in people with Acute Ischemic Stroke, run by China-Japan Union Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 30 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Guangxian Nan, MD, Ph.D (+86 13404320500, nangx@jlu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with modified Rankin Scale (mRS) 0-1 (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2026.