Safety and Efficacy of Alteplase When Administered in Chinese Patients With Acute Ischemic Hemispheric Stroke Where Thrombolysis is Initiated Between 3 and 4.5 Hours After Stroke Onset

An Open Label, Multicenter, Single-arm Trial to Assess Safety and Efficacy of Alteplase (Rt-PA) in Chinese Patients With Acute Ischemic Hemispheric Stroke Where Thrombolysis is Initiated Between 3 and 4.5 Hours After Stroke Onset

To evaluate the safety and efficacy of alteplase when administered between 3 and 4.5 hours after onset of stroke symptoms in Chinese patients with acute ischemic stroke

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Drug: alteplase

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100050
    • Beijing Tiantan Hospital affiliated to Cap Med University
  • Changchun, China, 130031
    • First Hospital of Jilin University
  • Dongguan, China, 523059
    • Dongguan People's Hospital
  • Fuzhou, China, 350025
    • No.900 Hospital of PLA Joint Logistics Support Force
  • Guangzhou, China, 510630
    • The First Affiliated Hospital of Jinan University
  • Guangzhou, China, 510150
    • Third Affiliated Hospital of Guangzhou Medical University
  • Shenyang, China, 110015
    • General Hospital of Shenyang Military Region
  • Tianjin, China, 300052
    • Tianjin Medical University General Hospital
  • Wuhan, China, 430060
    • Renmin Hospital of Wuhan University
  • Xuzhou, China, 221009
    • Xuzhou Central Hospital
  • Yanji, China, 133000
    • Yanbian University Hospital

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:

Age >= 18 years at screening(visit 1A) but <= 80 years Signed and dated written informed consent in accordance with good clinical practice and local legislation prior to admission to the trial Diagnosis of ischemic stroke with a measureable neurological deficit on National Institute of Health Stroke Scale (NIHSS) Thrombolytic therapy can be initiated within 3 to 4.5 hours of stroke onset Further inclusion criteria apply

Exclusion criteria:

Evidence of intracranial haemorrhage (ICH) on the (Computer Tomography) CT/(Magnetic Resonance Imaging)MRI-scan or symptoms suggestive of subarachnoid haemorrhage, even if the CT/MRI-scan is normal Acute bleeding diathesis Severe stroke as assessed clinically( e.g. National Institute of Health Stroke Scale>25) and/ or imaging demonstrates multi-lobar infarction (hypodensity >1/3 cerebral hemisphere) Severe uncontrolled arterial hypertension, e.g. systolic blood pressure>185 mmHg or diastolic blood pressure>110mmHg, or aggressive management (intravenous medication) necessary to reduce blood pressure to these limits Blood glucose <50mg/ dL or >400 mg/dL Any history of prior stroke in previous 3 months, or any history of prior stroke with concomitant diabetes Seizure at stroke onset Further exclusion criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: alteplase	Drug: alteplase

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Patients With Modified Rankin Scale (mRS 0-1) (Favourable Outcome) Response at Day 90 After Stroke Onset by Face-to-face Interview With Patient	The percentage of patients with modified Rankin Scale (mRS 0-1) (favourable outcome) response at Visit 5 (Day 90) after stroke onset by face-to-face interview with patient. Modified Rankin Scale (mRS): 0 = no symptom at all, 1 = no significant disability, 2 = slight disability, 3 = moderate disability, 4 = moderately severe disability, 5 = severe disability, and 6 = dead.	90 days
The Percentage of Patients With Symptomatic Intracranial Haemorrhage (sICH) Centrally Evaluated by Data-monitoring Committee (DMC) Consultants According to European Cooperative Acute Stroke Study (ECASS) III Definition Within the Whole Study Period	The percentage of patients with symptomatic intracranial haemorrhage (sICH) centrally evaluated by data-monitoring committee (DMC) consultants according to European Cooperative Acute Stroke Study (ECASS) III definition within the whole study period. According to the protocol, sICH (ECASS III criteria) was defined as: any apparently extravascular blood in the brain or within the cranium that was associated with clinical deterioration (defined by an increase in the NIHSS score of 4 or more points), or that led to death and that was identified as the predominant cause of the neurological deterioration. sICH event was firstly evaluated by investigator. The DMC consultants evaluated all the patients with NIHSS score increase of at least 4 any time after treatment (including all fatal patients and sICH events evaluated by investigator). Wilson score confidence interval is presented.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Percentage of Global Outcome Responder at Day 90 if he/She Obtains the Following Results at Day 90 (for All of the 4 Endpoints) mRS Score of 0 to 1; Barthel Index Score >= 95; NIHSS Score of 0 to 1; Glasgow Outcome Scale Score of 1	Percentage of global outcome responder at day 90 if he/she obtains the following results at day 90 for the endpoints mRS score of 0 to 1; Barthel Index score >= 95; NIHSS score of 0 to 1; Glasgow Outcome Scale score of 1. mRS: 0 = no symptom at all, 1 = no significant disability, 2 = slight disability, 3 = moderate disability, 4 = moderately severe disability, 5 = severe disability, and 6 = dead. NIHSS is composed of 11 items, and for each item a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. Glasgow Outcome Score applies to patients with brain damage allowing the objective assessment of their recovery in five categories: 1 Good Recovery, 2 Moderately Disabled, 3 Severely Disabled, 4 Vegetative State, 5 Dead. Barthel Index score to measure performance in activities of daily living with the scale ranging from 0 to 100. Global outcome response is the intersection of above four respective outcomes.	90 days
Patient Survival Probability at Visit 5 (Censoring at Day 90)	Patient survival probability at visit 5 (censoring at day 90). The percentage of patients who died until Day 1, Day 7, Day 30, Day 90.	90 days
The Percentage of Patients With Death Related to Stroke or of Neurological Causes	The percentage of patients with death related to stroke or of neurological causes.	90 days
The Percentage of Patients With Severity of Adverse Events	The percentage of patients with severity of adverse events (AEs). The percentage of patients with different categories of AEs are presented.	On-treatment period, that is, within 7 days from the start of bolus
The Percentage of Patients With Incidence of Cerebral Herniation and Symptomatic Edema	The percentage of patients with incidence of cerebral herniation and symptomatic edema.	90 days

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

General Publications

• Zheng H, Yang Y, Chen H, Li C, Chen Y, Shi FD, Yang L, Cui X, Lu Z, Liang Y, Cui S, Xu A, Wu Y, Sun Y, Wang Y. Thrombolysis with alteplase 3-4.5 hours after acute ischaemic stroke: the first multicentre, phase III trial in China. Stroke Vasc Neurol. 2020 Sep;5(3):285-290. doi: 10.1136/svn-2020-000337. Epub 2020 May 28.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2016
• Primary Completion (Actual): December 11, 2017
• Study Completion (Actual): December 11, 2017

Study Registration Dates

• First Submitted: October 10, 2016
• First Submitted That Met QC Criteria: October 10, 2016
• First Posted (Estimate): October 12, 2016

Study Record Updates

• Last Update Posted (Actual): August 5, 2019
• Last Update Submitted That Met QC Criteria: August 2, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tissue Plasminogen Activator
• Other Study ID Numbers: 135.331