Evaluation Of HUK in Acute Stroke Patients: MRS and CTP

Evaluation Of Human Urinary Kallidinogenase in Acute Stroke Patients: Magnetic Resonance Spectrum and CT Perfusion

Background: Acute ischemic stroke (AIS) is a leading cause of morbidity and mortality worldwide. Human urinary kallidinogenase (HUK), a glycoprotein extracted from male urine currently used in China for enhancing cerebral perfusion5, plays a neuroprotective role including promoting angiogenesis, enhancing cerebral perfusion and suppressing the inflammatory response in animals and in patients with respect to regulating the kallikrein-kinin system. In previous clinical research, neurological function scores and cerebral perfusion scans were largely used to evaluate the efficiency of HUK. However, the mechanisms of Further well-conducted, randomized controlled studies using HUK are currently lacking.

Objective: To assess the Human urinary kallidinogenase effects on brain metabolite and cerebral perfusion changes using magnetic resonance spectroscopy and CT perfusion in patients with AIS.

Methods: The investigators plan to do a single-centre randomized, double-blind, controlled trial in which ischemic stroke patients will be randomized to treatment with either HUK or regular treatment within 72 hours of symptom onset. The study includes two MRS and two CTP scannings (before and after 2 week treatment) for all randomized subjects.

The endpoints will include improvement of the NIH Stroke Scale (NIHSS) score from baseline, modified Rankin scale (mRS) score and Barthel index at 14 days.

EvHUKMRS will test the following hypotheses:

1. HUK enhanced N-acetylaspartate (NAA) and cerebral blood flow (CBF) 14 days after treatment compared with control group.
2. HUK group compared to control group when administered 72 hours after onset of AIS improves recovery and functional outcome as assessed by improvement of NIHSS score , mRS score and BI score on day 14 post-stroke.

A positive result will have a significant impact in the management of AIS and pave the way for future studies aimed at finding the optimal dose and formulation of HUK for treating acute ischemic stroke.

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Human urinary kallidinogenase (HUK); Drug: aspirin® , clopidogrel® , atorvastatin®

Detailed Description

A)Specific Primary Objective:

1. To determine if HUK, administered within 72 hours of AIS onset is superior to regular treatment in improving NAA values and CBF on day 14 post stroke.

B) Specific Secondary Objectives:

1. To determine if HUK, administered within 72 hours of AIS onset is superior to regular treatment in reducing neurological deficit and improving functional outcome on day 14 post stroke.

Recruitment of study subjects:

Acute ischemic stroke patients admitted to the Neurology department in XWh (Xuan hospital) during the study period who are eligible to participate in this study based on criteria stated above will be invited to participate in this study.

The time window for enrolment will be within 72 hours of symptom onset. All eligible patients will be identified by the ward and on-call Neurology/Medical teams and referred to the study research assistants or investigators; who will then screen the patient for participation in this trial.

STUDY INTERVENTION The assigned treatment 0.15 PNA units of HUK injection or regular treatment will be administered once daily for 14 consecutive days soon after informed consent is taken and the patient is enrolled into the study.

Follow-up Assessment:

The neurologic deficits, global functional abilities and level of handicap will be scored using the NIH Stroke Scale (NIHSS) and the modified Rankin scale (mRS) at baseline and on day 14(plus or minus 14 days).

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ages ranging from 18 to 80 years
• onset time less than 72 h, NIHSS score ≥4;

Exclusion Criteria:

• TIA
• patients with contraindication of venous thrombolysis
• patients with encephalic bleeding disorder
• patients with incomplete hepatic and renal function
• patients with a medical history of peptic ulcer, haemorrhagic stroke, brain tumour or brain trauma
• patients who could not coordinate with an MRS scan and
• patients with vertebral basilar artery system infarction.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Kallikrein group; Subjects receive kailikang treatment according to real clinical practice (suggest above 14 days treatment),0.15 peptide nucleic acids(PNA), once a day.	Drug: Human urinary kallidinogenase (HUK); Human urinary kallidinogenase can transform kininogen to bradykinin (kinin) and vasodilatory factors (kallidin)
Sham Comparator: Control group; Patients in control group will receive foundation treatment, including aspirin® (100 mg/d), clopidogrel® (75 mg/d), and atorvastatin® (20 mg/d) for 14 days	Drug: aspirin® , clopidogrel® , atorvastatin®; Patients in control group will receive foundation treatment, including aspirin® (100 mg/d), clopidogrel® (75 mg/d), and atorvastatin® (20 mg/d) for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
N-acetylaspartate as measured on Magnetic Resonance Spectrum study on admission	NAA Admit	14 days
Creatine as measured on Magnetic Resonance Spectrum study on admission	Cr Admit	14 days
Cholineas measured on Magnetic Resonance Spectrum study on admission	Cho	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of mordified Rankin Scale		14 days
The proportion of NIHSS		14 days
The proportion of mRS		14 days
Cerebral blood flow as measured on CT perfusion study on admission	CBF Admit	14 days
Cerebral blood volume as measured on CT perfusion study on admission	CBV Admit	14 days
Mean transit time as measured on CT perfusion study on admission	MTT Admit	14 days
Time to peak as measured on CT perfusion study on admission	TTP Admit	14 days

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Investigators: Study Chair: Moli Wang, 1, Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2014
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: December 5, 2017
• First Submitted That Met QC Criteria: February 12, 2018
• First Posted (Actual): February 13, 2018

Study Record Updates

• Last Update Posted (Actual): February 13, 2018
• Last Update Submitted That Met QC Criteria: February 12, 2018
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Magnetic resonance spectroscopy; Acute ischemic stroke; Human Urinary Kallidinogenase; CT perfusion
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Coagulants; Reproductive Control Agents; Fertility Agents; Fertility Agents, Male; Aspirin; Atorvastatin; Clopidogrel; Kallikreins
• Other Study ID Numbers: mrsctpzyf

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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