Evaluation Of HUK in Acute Stroke Patients: MRS and CTP
Condition: Acute Ischemic Stroke
MeSH terms: Stroke; Ischemic Stroke
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

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).
    

Intervention name(s): Human urinary kallidinogenase (HUK); aspirin® , clopidogrel® , atorvastatin®
Intervention type(s): Drug; Drug
Intervention description(s): Human urinary kallidinogenase can transform kininogen to bradykinin (kinin) and vasodilatory factors (kallidin); 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
Intervention MeSH terms: Aspirin; Kallikreins; Clopidogrel; Atorvastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Human Urinary Kallidinogenase; Acute ischemic stroke; Magnetic resonance spectroscopy; CT perfusion