Efficacy and Safety of Human Urinary Kallidinogenase Combined With Endovascular Therapy in Acute Ischemic Stroke With Large Vessel Occlusion (HEAL)

Efficacy and Safety of Human Urinary Kallidinogenase Combined With Endovascular Therapy in Acute Ischemic Stroke With Large Vessel Occlusion: A Prospective, Randomized, Double-blind, Placebo-controlled, Multi-center Study

The purpose of this study is to evaluate the safety and efficacy of Human Urinary Kallidinogenase combined with endovascular therapy in acute ischemic stroke (AIS) patients with large vessel occlusion.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Experimental: Human Urinary Kallidinogenase; Drug: Placebo Comparator: Placebo

Detailed Description

A prospective, randomized, double-blind, placebo-controlled, multi-center study of Human Urinary Kallidinogenase or Placebo, combined with endovascular therapy for AIS patients with large vessel occlusion.

Approximately 120 eligible subjects will be randomized (1:1) to receive one of the following treatments for 10 days:

• Human Urinary Kallidinogenase combined with endovascular therapy (non-bridged)
• Placebo combined with endovascular therapy (non-bridged) Primary efficacy of Human Urinary Kallidinogenase will be evaluated at 90 days. The safety of Human Urinary Kallidinogenase will be evaluated through 90 days. End of study evaluation will occur at day 90 or premature discontinuation.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Qiang Dong, M.D.; Phone Number: 13701747065; Email: 13701747065@163.com
• Study Contact Backup: Name: Wenjie Cao, M.D.; Phone Number: 13918206324; Email: wenjiecao@fudan.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Participant with acute anterior circulation ischemic stroke receiving endovascular treatment within 24 hours (non-bridged).
2. Age ≥18 years old and ≤80 years old.
3. The mRS score was 0-1 before onset.
4. ASPECT score of infarction on emergency CT ≥7.
5. Emergency CTA indicating AIS with large vessel occlusion (internal carotid artery, M1 or M2 segment of middle cerebral artery).
6. Emergency CTP or DWI suggesting infarct core body ≥10 mL and <100 mL, and low perfusion brain tissue volume/ infarct core volume> 1.2.
7. Participant is willing and able to comply with the study protocol, and sign the informed consent form (patient or surrogate).

Exclusion Criteria:

1. Participant with severe heart, liver and kidney dysfunction, coagulation dysfunction, intolerance to surgery, Human Urinary Kallidinogenase allergy, contrast agent allergy or other angiographic contraindications.
2. CT or MRI showed intracranial hemorrhagic diseases (such as hemorrhagic stroke, epidural hematoma, intracranial hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, etc.).
3. Participant with previous cerebral hemorrhage, brain tumor, brain trauma or other brain diseases.
4. Taking ACEI antihypertensive drugs regularly and could not stop.
5. Participant with major surgery or severe trauma in the past 2 weeks.
6. Poor compliance and cannot fully follow the study protocol.
7. Pregnancy or lactation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo Comparator: Placebo; Before the first day of endovascular therapy (non-bridging), dissolve placebo in 100 mL 0.9% sodium chloride for intravenous injection, for the next 9 days, once a day for a total of 10 days.
Experimental: Human Urinary Kallidinogenase	Drug: Experimental: Human Urinary Kallidinogenase; Before the first day of endovascular therapy (non-bridging), dissolve Human Urinary Kallidinogenase in 100 mL 0.9% sodium chloride for intravenous injection, for the next 9 days, once a day for a total of 10 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
ASPECT score evaluated using routine CT	on day 7 after EVT
Modified Rankin Scale (mRS) score	on day 90 after EVT

Secondary Outcome Measures

Outcome Measure	Time Frame
Barthel index	on day 10 and 90 after EVT
Percentage of TIC ≥ 2b and mRS ≤2	on day 90 after EVT
Changes of NIH Stroke Scale(NIHSS) score from baseline	day 1, 4, 7 and 10 after EVT
Changes of vital signs from baseline	day 1, 4, 7 and 10 after EVT
Changes of blood inflammatory index and vascular endothelial cell growth index from day 1 after EVT	day 7 after EVT
MRI and / or DWI examined	within 10 days to determine the infarct volume
Recurrence rate of ischemic stroke	within 90 days after EVT

Collaborators and Investigators

• Sponsor: Huashan Hospital
• Collaborators: Shanghai Stroke Association
• Investigators: Principal Investigator: Qiang Dong, M.D., Huashan Hospital; Principal Investigator: Wenjie Cao, M.D., Huashan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: December 28, 2023
• First Submitted That Met QC Criteria: January 9, 2024
• First Posted (Actual): January 18, 2024

Study Record Updates

• Last Update Posted (Actual): April 4, 2024
• Last Update Submitted That Met QC Criteria: April 3, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Physiological Effects of Drugs; Coagulants; Reproductive Control Agents; Fertility Agents; Fertility Agents, Male; Kallikreins
• Other Study ID Numbers: KY2023-707

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No