Thrombolysis of Urokinase for Minor Stroke
Condition: Minor Stroke
MeSH terms: Stroke
Study type: Interventional
Phase: Phase 3

Summary: 
      This trial will enroll patients that have been diagnosed with minor stroke, which has
      occurred within the past 6 hours. TRUST is a prospective multicenter, randomized,
      blinded-endpoint study to evaluate the efficacy and safety of Urokinase Thrombolysis for
      patients with minor stroke.
    

Detailed description: 
      China is currently faced with the heaviest stroke burden due to the tremendous population and
      susceptibility to cerebrovascular disease. As has been assessed, deaths caused by
      cerebrovascular disease are three times of cardiovascular disease. Within whole population
      with cerebrovascular disease, minor stoke have taken a significant part of the disease
      burden. Thus the population with minor stoke is one of the most important parts in efficient
      prevention of cerebrovascular disease. According to phase I and II data from national stoke
      registration in China, 35.25% to 42.23% cases were minor ischemic strokes. However, in
      clinical practice, the minor ischemic stroke patients are likely to be ignored and some might
      have poor prognosis. As has been demonstrated by a number of studies, up to one third of the
      acute non-disabling ischemic stroke without in-time thrombolysis may suffer from disabling or
      death at 90-day follow-up.

      Several studies have demonstrated the potential benefits of thrombolysis compared usually
      with placebo, including the Third International Stroke Trail ( IST-3, rt-PA to placebo,
      patients within 3 hours after attack, with blood pressure lower than 185/110mmHg and
      NIHSS≤5)，National Institute of Neurological Disorders and Stroke rt-PA Stroke Study（ NINDS,
      rt-PA to placebo, patients with mild ischemic stroke recognized by 5 different definitions）.

      Urokinase is a kind of non-selective plasminogen activator, urokinase acted as effective
      catalyzer in the transferring of both free and protein-binding plasminogen to plasmin, thus
      inducing thrombolysis. As one of the widely used medication for intravenous thrombolysis in
      China, urokinase has been suggested the the efficacy and safety for ischemic stroke. With
      easier availability and lower price, urokinase has provided a promising alternation to
      patients who need thrombolysis in China, especially in less developed areas. The Chinese
      guideline for diagnosis and treatment of acute ischemic stroke 2018 has recommended urokinase
      as an alternation in the treatment of acute ischemic stroke within 6-hour time window as
      well, if rt-PA is not available or affordable. However, randomized and multicenter clinical
      trial of urokinase thrombolysis for minor stroke is still vacant, which couldn't provide more
      persuasive evidence.

      TRUST is a prospective multicenter, randomized, single-blind evaluation study to evaluate the
      efficacy and safety of Urokinase Thrombolysis for patients with minor stroke. The trail will
      enroll a total of 1002 minor stroke patients within a 6 hour time window with a NIHSS score
      ≤5 at the time of randomization. Randomization will be 1:1 to Urokinase Thrombolysis
      (experimental) or Antiplatelet agents (control). Patients will receive 1 million units
      urokinase dissolved by 100ml saline through intravenous infusion within 30min or oral
      antiplatelet agents. All patients will undergo CT or MRI before treatment and will undergo
      the second CT within 36 hours after treatment. Patients will be followed up at 36h, 7d and 90
      days. The primary outcome measures including the proportion of patients with a modified
      Rankin Scale(mRS) of 0 or 1 at 90-day follow-up and the patients with symptomatic
      intracranial hemorrhage within 36 hours. Secondary outcome measures cover new vascular
      events, the Progress of MRS score, Neurological impairment, Daily function evaluations,
      Quality of life assessments, Overall mortality and Adverse events and severe adverse events
      within 90 days.
    

Intervention name(s): Urokinase thrombolysis; Aspirin;Clopidogrel
Intervention type(s): Drug; Drug
Intervention description(s): The patients of intervention group will receive 1 millions units urokinase dissolved by 100 saline through intravenous infusion within 30 minutes.; The control group will receive antiplatelet agents as decided by the physicians according to Chinese guideline for diagnosis and treatment of acute ischemic stroke 2018.
Other intervention name(s): Urokinase; Antiplatelet treatment
Intervention MeSH terms: Aspirin; Clopidogrel
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Thrombolysis; Urokinase; Ischemic stroke