Temporal Trends of Thrombolysis Treatment in Chinese Acute Ischemic Stroke (AIS) Patients From 2007-2017: Analysis of China National Stroke Registry (CNSR) I, II, and III; CTP-Draft Review Performed;

Temporal Trends of Thrombolysis Treatment in Chinese Acute Ischemic Stroke (AIS) Patients From 2007 2017: Analysis of China National Stroke Registry (CNSR) I, II, and III

The present study is to be conducted based on the AIS patient data collected from CNSR I, II, and III.

The primary objectives are:

• To investigate the temporal changes in the proportion of intravenous recombinant plasminogen activator (IV rtPA) treatment from 2007 to 2017 among Intravenous Thrombolytics (IVT) eligible patients (patient groups B and B') and overall AIS patients (patient group A) in China;
• To investigate the temporal changes in IV rtPA treatment time intervals from 2007 to 2017 among IV rtPA treated patients (patient groups C and C') in China.

The secondary objectives are:

- To describe the demographic and clinical characteristics of the IV rtPA treated patients (patient groups C and C'), IVT eligible patients (patient groups B and B') and the overall AIS patients (patient group A) from 2007 to 2017 from the CNSR I to III.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Drug: IV rtPA (intravenous recombinant plasminogen activator)

• Study Type: Observational
• Enrollment (Actual): 42188

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100070
    • Beijing Tiantan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

All eligible patients from the CNSR I to III will be included. Patient groups include the overall AIS patients (patient group A), IVT eligible patients (patient groups B and B'), and IV rtPA treated patients (patient groups C and C').

Description

Inclusion Criteria:

• Patient group A: All AIS patients

  • Aged 18 80 years
  • Diagnosed with AIS on admission

• Patient groups B and B': IVT eligible patients

  • Met the in- and exclusion criteria of "all AIS patients"
  • Arrived at hospital within 2 h (patient group B) or 3.5 h (patient group B') of symptom onset

• Patient groups C and C': IV rtPA treated patients

  • Met the in- and exclusion criteria of "IVT eligible patients"
  • Treated with IV rtPA within 3 h (patient group C) or 4.5 h (patient group C') of symptom onset

Exclusion Criteria:

• Patient group A: All AIS patients

  • Missing baseline data including age and gender
  • Diagnosed with intracranial hemorrhage (ICH), Transient Ischemic Attack (TIA), subarachnoid hemorrhage (SAH), or unspecific stroke
  • Arrived at hospital after 7 days of symptom onset

• Patient groups B and B': IVT eligible patients

  • Missing key data including:

    i. symptom onset time (or last known well time) ii. hospital arrival time iii. whether received IVT treatment or not iv. the time of IVT treatment

  • Documented IVT absolute contraindications, according to the case report form (CRF) for each wave of CNSR

• Patient groups C and C': IV rtPA treated patients

  • Not received IVT
  • Received IVT other than rtPA
  • Treated with IV rtPA after 3 h (patient group C) or 4.5 h (patient group C') of symptom onset
  • Received additional treatments with intra arterial reperfusion or experimental therapies

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CNSR I (2007 to 2008); For this group following patients will be analysed: The overall AIS patients aged 18 to 80 years who arrived at hospital within 7 days of symptom onset (Patient group A) Thereof: IVT eligible patients: AIS patients who arrived at hospital within 2 hours (patient group B) and 3.5 hours (patient group B') of symptom onset and with no documented absolute contraindications to IVT treatment Thereof: IV rtPA treated patients: IVT eligible patients who arrived at hospital within 2 hours of symptom onset and received IV rtPA within 3 hours of symptom onset (patient group C) and those who arrived at hospital within 3.5 hours of symptom onset and received IV rtPA within 4.5 hours of symptom onset (patient group C')	Drug: IV rtPA (intravenous recombinant plasminogen activator); intravenous injection
CNSR II (2012 to 2013); For this group following patients will be analysed: The overall AIS patients aged 18 to 80 years who arrived at hospital within 7 days of symptom onset (Patient group A) Thereof: IVT eligible patients: AIS patients who arrived at hospital within 2 hours (patient group B) and 3.5 hours (patient group B') of symptom onset and with no documented absolute contraindications to IVT treatment Thereof: IV rtPA treated patients: IVT eligible patients who arrived at hospital within 2 hours of symptom onset and received IV rtPA within 3 hours of symptom onset (patient group C) and those who arrived at hospital within 3.5 hours of symptom onset and received IV rtPA within 4.5 hours of symptom onset (patient group C')	Drug: IV rtPA (intravenous recombinant plasminogen activator); intravenous injection
CNSR III (2015 to 2017); For this group following patients will be analysed: The overall AIS patients aged 18 to 80 years who arrived at hospital within 7 days of symptom onset (Patient group A) Thereof: IVT eligible patients: AIS patients who arrived at hospital within 2 hours (patient group B) and 3.5 hours (patient group B') of symptom onset and with no documented absolute contraindications to IVT treatment Thereof: IV rtPA treated patients: IVT eligible patients who arrived at hospital within 2 hours of symptom onset and received IV rtPA within 3 hours of symptom onset (patient group C) and those who arrived at hospital within 3.5 hours of symptom onset and received IV rtPA within 4.5 hours of symptom onset (patient group C')	Drug: IV rtPA (intravenous recombinant plasminogen activator); intravenous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Who Received Intravenous Recombinant Plasminogen Activator (IV-rtPA) Treatment Within 3 Hours of Symptom Onset Among 2 Hours Intravenous Thrombolytics (IVT) Eligible Patients	The percentage of patients who received Intravenous Recombinant Plasminogen Activator (IV-rtPA) treatment within 3 hours of symptom onset among patients eligible for intravenous thrombolytics (IVT) who arrived at the hospital within 2 hours since symptom onset was reported.	From 2007 to 2017, up to 10 years before this study started.
Percentage of Patients Who Received Intravenous Recombinant Plasminogen Activator (IV-rtPA) Treatment Within 4.5 Hours of Symptom Onset Among 3.5 Hours Intravenous Thrombolytics (IVT) Eligible Patients	The percentage of patients who received Intravenous Recombinant Plasminogen Activator (IV-rtPA) treatment within 4.5 hours of symptom onset among patients eligible for intravenous thrombolytics (IVT) who arrived at the hospital within 3.5 hours since symptom onset was reported.	From 2007 to 2017, up to 10 years before this study started.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients Who Arrived at Hospital Within 2 Hours of Symptom Onset and Who Received Intravenous Recombinant Plasminogen Activator (IV-rtPA) Treatment Within 3 Hours of Symptom Onset Among All Eligible Patients	Percentage of patients who arrived at hospital within 2 hours of symptom onset and who received Intravenous Recombinant Plasminogen Activator (IV-rtPA) treatment within 3 hours of symptom onset among all eligible patients was reported.	From 2007 to 2017, up to 10 years before this study started.
Percentage of Patients Who Arrived at Hospital Within 3.5 Hours of Symptom Onset and Who Received Intravenous Recombinant Plasminogen Activator (IV-rtPA) Treatment Within 4.5 Hours of Symptom Onset Among All Eligible Patients	Percentage of patients who arrived at hospital within 3.5 hours of symptom onset and who received Intravenous Recombinant Plasminogen Activator (IV-rtPA) treatment within 4.5 hours of symptom onset among all eligible patients was reported.	From 2007 to 2017, up to 10 years before this study started.
The Door to Needle (DTN) Time (Time Between Arrival at Hospital and the Administration of Intravenous Recombinant Plasminogen Activator (IV-rtPA) Treatment) Among 3 Hours IV-rtPA Treated Patients	The door to needle (DTN) time (time between arrival at hospital and the administration of Intravenous Recombinant Plasminogen Activator (IV-rtPA) treatment) among patients who were treated with Intravenous Recombinant Plasminogen Activator (IV-rtPA) within 3 hours since symptom onset was reported.	From arrival at the hospital until the administration of Intravenous Recombinant Plasminogen Activator, up to 170 minutes.
Percentage of Patients With Door to Needle (DTN) Time (Time Between Arrival at Hospital and the Administration of Intravenous Recombinant Plasminogen Activator (IV-rtPA) Treatment) ≤ 60 Minutes Among 3 Hours IV-rtPA Treated Patients	The percentage of patients with door to needle (DTN) time (time between arrival at hospital and the administration of Intravenous Recombinant Plasminogen Activator (IV-rtPA) treatment) ≤ 60 minutes among patients who were treated with Intravenous Recombinant Plasminogen Activator (IV-rtPA) within 3 hours since symptom onset was reported.	From 2007 to 2017, up to 10 years before this study started.
Time Between Symptom Onset and Arrival at Hospital Among 3 Hours Intravenous Recombinant Plasminogen Activator (IV-rtPA) Treated Patients	Time between symptom onset and arrival at hospital among patients who were treated with Intravenous Recombinant Plasminogen Activator (IV-rtPA) within 3 hours since symptom onset was reported.	From symptom onset until arrival at the hospital, up to 120 minutes.
Time Between Symptom Onset and the Administration of Intravenous Recombinant Plasminogen Activator (IV-rtPA) Treatment Among 3 Hours IV-rtPA Treated Patients	Time between symptom onset and the administration of Intravenous Recombinant Plasminogen Activator (IV-rtPA) treatment among patients who were treated with Intravenous Recombinant Plasminogen Activator (IV-rtPA) within 3 hours since symptom onset was reported.	From symptom onset until administration of Intravenous Recombinant Plasminogen Activator, up to 180 minutes.
The Door to Needle (DTN) Time (Time Between Arrival at Hospital and the Administration of Intravenous Recombinant Plasminogen Activator (IV-rtPA) Treatment) Among 4.5 Hours IV-rtPA Treated Patients	The door to needle (DTN) time (time between arrival at hospital and the administration of Intravenous Recombinant Plasminogen Activator (IV-rtPA) treatment) among patients who were treated with Intravenous Recombinant Plasminogen Activator (IV-rtPA) within 4.5 hours since symptom onset was reported.	From arrival at the hospital until the administration of Intravenous Recombinant Plasminogen Activator, up to 247 minutes.
Percentage of Patients With Door to Needle (DTN) Time (Time Between Arrival at Hospital and the Administration of Intravenous Recombinant Plasminogen Activator (IV-rtPA) Treatment) ≤ 60 Minutes Among 4.5 Hours IV-rtPA Treated Patients	The percentage of patients with door to needle (DTN) time (time between arrival at hospital and the administration of Intravenous Recombinant Plasminogen Activator (IV-rtPA) treatment) ≤ 60 minutes among patients who were treated with Intravenous Recombinant Plasminogen Activator (IV-rtPA) within 4.5 hours since symptom onset was reported.	From 2007 to 2017, up to 10 years before this study started.
Time Between Symptom Onset and Arrival at Hospital Among 4.5 Hours Intravenous Recombinant Plasminogen Activator (IV-rtPA) Treated Patients	Time between symptom onset and arrival at hospital among patients who were treated with Intravenous Recombinant Plasminogen Activator (IV-rtPA) within 4.5 hours since symptom onset was reported	From symptom onset until arrival at the hospital, up to 210 minutes.
Time Between Symptom Onset and the Administration of Intravenous Recombinant Plasminogen Activator (IV-rtPA) Treatment Among 4.5 Hours IV-rtPA Treated Patients	Time between symptom onset and the administration of Intravenous Recombinant Plasminogen Activator (IV-rtPA) treatment among patients who were treated with Intravenous Recombinant Plasminogen Activator (IV-rtPA) within 4.5 hours since symptom onset was reported	From symptom onset until the administration of Intravenous Recombinant Plasminogen Activator, up to 270 minutes.

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2020
• Primary Completion (Actual): September 30, 2020
• Study Completion (Actual): September 30, 2020

Study Registration Dates

• First Submitted: February 27, 2020
• First Submitted That Met QC Criteria: February 27, 2020
• First Posted (Actual): March 2, 2020

Study Record Updates

• Last Update Posted (Actual): November 5, 2021
• Last Update Submitted That Met QC Criteria: November 4, 2021
• Last Verified: November 1, 2021

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; Ischemic Stroke; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Plasminogen
• Other Study ID Numbers: 0135-0343

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://trials.boehringer-ingelheim.com/trial_results/clinical_submission_documents.html to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link http://trials.boehringer-ingelheim.com/ to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

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