Ischaemic Stroke
Conditions
Brief summary
A non-interventional post-approval study on Safe Implementation of Treatment in Stroke - International Stroke Thrombolysis Register (SITS-ISTR) existing data of intravenous recombinant tissue plasminogen Activator (rt-PA) (0.9 mg/kg) in acute ischaemic stroke patients over 80 years, treated according to the Summary of Product Characteristics (SmPC) in European countries.
Interventions
DRUGAlteplase
Intravenous injection
Sponsors
Boehringer Ingelheim
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
80 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients over 80 years old presenting with acute ischaemic stroke symptoms for which thrombolysis treatment was initiated within 4.5 hours after stroke onset according to SmPC are included. * Patients over 80 years who received thrombolysis according to SmPC for acute ischaemic stroke (AIS) within 4.5 hours after stroke onset during the period (approximately 3 years) prior to July 2018 are included.
Exclusion criteria
* Contraindication(s) to the use of IV thrombolysis per local SmPC. * Documentation that the patient was enrolled or is planned to be enrolled in an investigational clinical trial at the time of the onset of index event and for the duration of the data collection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Symptomatic Intracerebral Haemorrhage (SICH) Per Safe Implementation of Thrombolysis - Stroke-Monitoring Study (SITS-MOST) Definition | Up to 36 hours after stroke onset, between June 2015 and December 2021 | Defined as the number of participants presenting intracerebral haemorrhage (parenchymatous haemorrhage type 2, PH2), at the 22-36 hours post-treatment scan or earlier, if clinically indicated, combined with neurological deterioration leading to an increase of 4 points on the National Institutes of Health Stroke Scale (NIHSS) from baseline to 24h or death within 24 hours (SITS-MOST definition). The NIHSS is a neurological examination tool used to objectively quantify stroke severity. It is composed by 11 items, 3 of which with more than one component, scoring between 0 (normal function) and 2, 3, 7 or 8 (highest degree of impairment) for a specific ability (item). The sum of the individual scores from each item originate the total NIHSS score, where: 0 = no stroke symptoms; 1-4 = minor stroke; 5-15 = moderate stroke; 16-20 = moderate to severe stroke; and 21-42 = severe stroke. |
| Mortality Within 90 Days, Defined as the Number of Participants With a Death Event | Up to 90 days after stroke onset, between June 2015 and December 2021 | Number of participants who died within 90 days as classified by the investigator according to cause: cerebral infarct, cerebral haemorrhage, cerebral infarct and haemorrhage unspecified, myocardial infarct, pulmonary embolism, pneumonia, other vascular cause, unknown and other cause of death. The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) was used. |
| Functional Independency, as Defined by a mRS (Modified Rankin Score) 0-2 Within 90 Days | Up to 90 days after stroke onset, between June 2015 and December 2021 | Defined as the number of participants classified with a modified Rankin score (mRS) of 0, 1 or 2 within 90 days. The mRS measures the degree of disability or dependence in the daily activities of people who have suffered a stroke. The score has a scale from 0 to 6, where: 0 = no symptoms at all; 1 = no significant disability despite symptoms, able to carry out all usual duties and activities; 2 = slight disability, unable to carry out all previous activities, but able to look after own affairs without assistance; 3 = moderate disability, requiring some help but able to walk without assistance; 4 = moderately severe disability, unable to walk without assistance and unable to attend own bodily needs without assistance; 5 = severe disability, bedridden, incontinent and requiring constant nursing care and attention; and 6 = dead. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From Onset of Symptoms to Start of Intravenous Thrombolysis (IVT) Treatment | Up to 4.5 hours after stroke onset, between June 2015 and December 2021 | Time in minutes from the onset of ischaemic stroke symptoms to start of treatment with intravenous thrombolysis with Actilyse® (alteplase). |
| Stroke Severity, Defined by the National Institute of Health's Stroke Scale (NIHSS) | At baseline, defined as the ischaemic stroke hospital admission date, between June 2015 and December 2021 | Defined by the total National Institutes of Health Stroke Scale (NIHSS) score presented by the participants of each group at baseline. The NIHSS is a neurological examination tool used to objectively quantify stroke severity. It is composed by 11 items, 3 of which with more than one component, scoring between 0 (normal function) and 2, 3, 7 or 8 (highest degree of impairment) for a specific ability (item). The sum of the individual scores from each item originate the total NIHSS score, where: 0 = no stroke symptoms; 1-4 = minor stroke; 5-15 = moderate stroke; 16-20 = moderate to severe stroke; and 21-42 = severe stroke. |
| Door to Needle Time | Up to 4.5 hours after stroke onset, between June 2015 and December 2021 | Time in minutes from hospital door or registry arrival at the hospital to start of treatment with intravenous thrombolysis (IVT) with Actilyse® (alteplase) |
| Time From Onset of Symptoms to Door (or Captured in the Registry Arrival at the Hospital) | Up to 4.5 hours after stroke onset, between June 2015 and December 2021 | Time in minutes from the onset of ischaemic stroke symptoms to hospital door or the registry arrival at the hospital. |
| Number of Participants With a Modified Rankin Score (mRS) of 0-1 Within 90 Days | Up to 90 days after stroke onset, between June 2015 and December 2021 | Defined as the number of participants achieving of a modified Rankin score (mRS) of 0 or 1 within 90 days. The mRS measures the degree of disability or dependence in the daily activities of people who have suffered a stroke. The score has a scale from 0 to 6, where: 0 = no symptoms at all; 1 = no significant disability despite symptoms, able to carry out all usual duties and activities; 2 = slight disability, unable to carry out all previous activities, but able to look after own affairs without assistance; 3 = moderate disability, requiring some help but able to walk without assistance; 4 = moderately severe disability, unable to walk without assistance and unable to attend own bodily needs without assistance; 5 = severe disability, bedridden, incontinent and requiring constant nursing care and attention; and 6 = dead. |
| Number of Participants With Symptomatic Intracerebral Haemorrhage (SICH) Per European Cooperative Acute Stroke Study 2 (ECASS 2) Definition | Up to 7 days after stroke onset, between June 2015 and December 2021 | Defined as the number of participants with any intracerebral haemorrhage including haemorrhagic infarctions at the 22-36 hours post-treatment scan combined with neurological deterioration leading to an increase of 4 points on the National Institutes of Health Stroke Scale (NIHSS) or death within 7 days. The NIHSS is a neurological examination tool used to objectively quantify stroke severity.It is composed by 11 items, 3 of which with more than one component, scoring between 0 (normal function) and 2, 3, 7 or 8 (highest degree of impairment) for a specific ability (item). The sum of the individual scores from each item originate the total NIHSS score, where: 0 = no stroke symptoms; 1-4 = minor stroke; 5-15 = moderate stroke; 16-20 = moderate to severe stroke; and 21-42 = severe stroke. |
Countries
Sweden
Participant flow
Recruitment details
Observational retrospective study based on existing data collected from the Safe Implementation of Treatment in Stroke-International Stroke Treatment Registry (SITS-ISTR) of ischaemic stroke patients older than 80 years of age treated with Actilyse® (alteplase) according to the Summary of Product Characteristics (SmPC) criteria during post-approval and pre-approval periods.
Pre-assignment details
The patients were selected based on the sites fulfilling the criteria defined and treated according to the Summary of Product Characteristics (SmPC) of Actilyse® (alteplase) during pre-approval and post-approval period. The data was collected between June 2015 and December 2021. A patient was excluded from the entire cohort when had missing data on one of the selection steps.
Participants by arm
| Arm | Count |
|---|---|
| Actilyse® (Alteplase) Pre-approval Patients older than 80 years presenting acute ischaemic stroke symptoms, between June 2015 and July 2018 (or the exact approval date), received once intravenous thrombolysis treatment with off-label Actilyse® (alteplase) within 4.5 hours after stroke onset, according to the Summary of Product Characteristics (SmPC). The recommended total dose was 0.9 milligrams (mg) alteplase per kilogram body weight (maximum of 90 mg) starting with 10% of the total dose as an initial intravenous bolus, immediately followed by the remainder of the total dose infused intravenously over 60 minutes. | 614 |
| Actilyse® (Alteplase) Post-approval Patients older than 80 years old presenting acute ischaemic stroke symptoms, between 1st July 2018 (or the first day of the next month after exact approval date) to December 2021, received once intravenous thrombolysis treatment with Actilyse® (alteplase) within 4.5 hours after stroke onset, according to the Summary of Product Characteristics (SmPC). The recommended total dose was 0.9 milligrams (mg) alteplase per kilogram body weight (maximum of 90 mg) starting with 10% of the total dose as an initial intravenous bolus, immediately followed by the remainder of the total dose infused intravenously over 60 minutes. | 614 |
| Total | 1,228 |
Baseline characteristics
| Characteristic | Actilyse® (Alteplase) Pre-approval | Actilyse® (Alteplase) Post-approval | Total |
|---|---|---|---|
| Age, Continuous | 86.6 Years STANDARD_DEVIATION 4.1 | 86.6 Years STANDARD_DEVIATION 4.3 | 86.6 Years STANDARD_DEVIATION 4.2 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 377 Participants | 374 Participants | 751 Participants |
| Sex: Female, Male Male | 237 Participants | 240 Participants | 477 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Functional Independency, as Defined by a mRS (Modified Rankin Score) 0-2 Within 90 Days
Defined as the number of participants classified with a modified Rankin score (mRS) of 0, 1 or 2 within 90 days. The mRS measures the degree of disability or dependence in the daily activities of people who have suffered a stroke. The score has a scale from 0 to 6, where: 0 = no symptoms at all; 1 = no significant disability despite symptoms, able to carry out all usual duties and activities; 2 = slight disability, unable to carry out all previous activities, but able to look after own affairs without assistance; 3 = moderate disability, requiring some help but able to walk without assistance; 4 = moderately severe disability, unable to walk without assistance and unable to attend own bodily needs without assistance; 5 = severe disability, bedridden, incontinent and requiring constant nursing care and attention; and 6 = dead.
Time frame: Up to 90 days after stroke onset, between June 2015 and December 2021
Population: Propensity score matched population based on the variables: age, sex, pre-stroke Modified Rankin Scale score, baseline National Institute of Health Stroke Scale, systolic blood pressure, glucose level, anti-platelet treatment at stroke onset, hypertension, diabetes, atrial fibrillation, hyperlipidaemia, smoking, previous stroke earlier than 3 months, stroke onset to intravenous thrombolysis treatment start time. Participants with missing values were excluded from the analysis of this outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Actilyse® (Alteplase) Pre-approval | Functional Independency, as Defined by a mRS (Modified Rankin Score) 0-2 Within 90 Days | 205 Participants |
| Actilyse® (Alteplase) Post-approval | Functional Independency, as Defined by a mRS (Modified Rankin Score) 0-2 Within 90 Days | 233 Participants |
p-value: 0.2895% CI: [0.942, 1.237]Chi-squared
Primary
Mortality Within 90 Days, Defined as the Number of Participants With a Death Event
Number of participants who died within 90 days as classified by the investigator according to cause: cerebral infarct, cerebral haemorrhage, cerebral infarct and haemorrhage unspecified, myocardial infarct, pulmonary embolism, pneumonia, other vascular cause, unknown and other cause of death. The International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) was used.
Time frame: Up to 90 days after stroke onset, between June 2015 and December 2021
Population: Propensity score matched population based on the variables: age, sex, pre-stroke Modified Rankin Scale score, baseline National Institute of Health Stroke Scale, systolic blood pressure, glucose level, anti-platelet treatment at stroke onset, hypertension, diabetes, atrial fibrillation, hyperlipidaemia, smoking, previous stroke earlier than 3 months, stroke onset to intravenous thrombolysis treatment start time. Participants with missing values were excluded from the analysis of this outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Actilyse® (Alteplase) Pre-approval | Mortality Within 90 Days, Defined as the Number of Participants With a Death Event | 161 Participants |
| Actilyse® (Alteplase) Post-approval | Mortality Within 90 Days, Defined as the Number of Participants With a Death Event | 149 Participants |
p-value: 0.25495% CI: [0.699, 1.08]Chi-squared
Primary
Number of Participants With Symptomatic Intracerebral Haemorrhage (SICH) Per Safe Implementation of Thrombolysis - Stroke-Monitoring Study (SITS-MOST) Definition
Defined as the number of participants presenting intracerebral haemorrhage (parenchymatous haemorrhage type 2, PH2), at the 22-36 hours post-treatment scan or earlier, if clinically indicated, combined with neurological deterioration leading to an increase of 4 points on the National Institutes of Health Stroke Scale (NIHSS) from baseline to 24h or death within 24 hours (SITS-MOST definition). The NIHSS is a neurological examination tool used to objectively quantify stroke severity. It is composed by 11 items, 3 of which with more than one component, scoring between 0 (normal function) and 2, 3, 7 or 8 (highest degree of impairment) for a specific ability (item). The sum of the individual scores from each item originate the total NIHSS score, where: 0 = no stroke symptoms; 1-4 = minor stroke; 5-15 = moderate stroke; 16-20 = moderate to severe stroke; and 21-42 = severe stroke.
Time frame: Up to 36 hours after stroke onset, between June 2015 and December 2021
Population: Propensity score matched population based on the variables: age, sex, pre-stroke Modified Rankin Scale score, baseline National Institute of Health Stroke Scale, systolic blood pressure, glucose level, anti-platelet treatment at stroke onset, hypertension, diabetes, atrial fibrillation, hyperlipidaemia, smoking, previous stroke earlier than 3 months, stroke onset to intravenous thrombolysis treatment start time. Participants with missing values were excluded from the analysis of this outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Actilyse® (Alteplase) Pre-approval | Number of Participants With Symptomatic Intracerebral Haemorrhage (SICH) Per Safe Implementation of Thrombolysis - Stroke-Monitoring Study (SITS-MOST) Definition | 14 Participants |
| Actilyse® (Alteplase) Post-approval | Number of Participants With Symptomatic Intracerebral Haemorrhage (SICH) Per Safe Implementation of Thrombolysis - Stroke-Monitoring Study (SITS-MOST) Definition | 15 Participants |
p-value: 195% CI: [0.345, 1.784]Chi-squared
Secondary
Door to Needle Time
Time in minutes from hospital door or registry arrival at the hospital to start of treatment with intravenous thrombolysis (IVT) with Actilyse® (alteplase)
Time frame: Up to 4.5 hours after stroke onset, between June 2015 and December 2021
Population: Propensity score matched population based on the variables: age, sex, pre-stroke Modified Rankin Scale score, baseline National Institute of Health Stroke Scale, systolic blood pressure, glucose level, anti-platelet treatment at stroke onset, hypertension, diabetes, atrial fibrillation, hyperlipidaemia, smoking, previous stroke earlier than 3 months, stroke onset to intravenous thrombolysis treatment start time.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Actilyse® (Alteplase) Pre-approval | Door to Needle Time | 46 Minutes |
| Actilyse® (Alteplase) Post-approval | Door to Needle Time | 48 Minutes |
p-value: 0.27595% CI: [-0.072, 0.156]Wilcoxon (Mann-Whitney)
Secondary
Number of Participants With a Modified Rankin Score (mRS) of 0-1 Within 90 Days
Defined as the number of participants achieving of a modified Rankin score (mRS) of 0 or 1 within 90 days. The mRS measures the degree of disability or dependence in the daily activities of people who have suffered a stroke. The score has a scale from 0 to 6, where: 0 = no symptoms at all; 1 = no significant disability despite symptoms, able to carry out all usual duties and activities; 2 = slight disability, unable to carry out all previous activities, but able to look after own affairs without assistance; 3 = moderate disability, requiring some help but able to walk without assistance; 4 = moderately severe disability, unable to walk without assistance and unable to attend own bodily needs without assistance; 5 = severe disability, bedridden, incontinent and requiring constant nursing care and attention; and 6 = dead.
Time frame: Up to 90 days after stroke onset, between June 2015 and December 2021
Population: Propensity score matched population based on the variables: age, sex, pre-stroke Modified Rankin Scale score, baseline National Institute of Health Stroke Scale, systolic blood pressure, glucose level, anti-platelet treatment at stroke onset, hypertension, diabetes, atrial fibrillation, hyperlipidaemia, smoking, previous stroke earlier than 3 months, stroke onset to intravenous thrombolysis treatment start time. Participants with missing values were excluded from the analysis of this outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Actilyse® (Alteplase) Pre-approval | Number of Participants With a Modified Rankin Score (mRS) of 0-1 Within 90 Days | 142 Participants |
| Actilyse® (Alteplase) Post-approval | Number of Participants With a Modified Rankin Score (mRS) of 0-1 Within 90 Days | 158 Participants |
p-value: 0.56195% CI: [0.872, 1.261]Chi-squared
Secondary
Number of Participants With Symptomatic Intracerebral Haemorrhage (SICH) Per European Cooperative Acute Stroke Study 2 (ECASS 2) Definition
Defined as the number of participants with any intracerebral haemorrhage including haemorrhagic infarctions at the 22-36 hours post-treatment scan combined with neurological deterioration leading to an increase of 4 points on the National Institutes of Health Stroke Scale (NIHSS) or death within 7 days. The NIHSS is a neurological examination tool used to objectively quantify stroke severity.It is composed by 11 items, 3 of which with more than one component, scoring between 0 (normal function) and 2, 3, 7 or 8 (highest degree of impairment) for a specific ability (item). The sum of the individual scores from each item originate the total NIHSS score, where: 0 = no stroke symptoms; 1-4 = minor stroke; 5-15 = moderate stroke; 16-20 = moderate to severe stroke; and 21-42 = severe stroke.
Time frame: Up to 7 days after stroke onset, between June 2015 and December 2021
Population: Propensity score matched population based on the variables: age, sex, pre-stroke Modified Rankin Scale score, baseline National Institute of Health Stroke Scale, systolic blood pressure, glucose level, anti-platelet treatment at stroke onset, hypertension, diabetes, atrial fibrillation, hyperlipidaemia, smoking, previous stroke earlier than 3 months, stroke onset to intravenous thrombolysis treatment start time. Participants with missing values were excluded from the analysis of this outcome.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Actilyse® (Alteplase) Pre-approval | Number of Participants With Symptomatic Intracerebral Haemorrhage (SICH) Per European Cooperative Acute Stroke Study 2 (ECASS 2) Definition | 24 Participants |
| Actilyse® (Alteplase) Post-approval | Number of Participants With Symptomatic Intracerebral Haemorrhage (SICH) Per European Cooperative Acute Stroke Study 2 (ECASS 2) Definition | 30 Participants |
p-value: 0.52295% CI: [0.707, 1.756]Chi-squared
Secondary
Stroke Severity, Defined by the National Institute of Health's Stroke Scale (NIHSS)
Defined by the total National Institutes of Health Stroke Scale (NIHSS) score presented by the participants of each group at baseline. The NIHSS is a neurological examination tool used to objectively quantify stroke severity. It is composed by 11 items, 3 of which with more than one component, scoring between 0 (normal function) and 2, 3, 7 or 8 (highest degree of impairment) for a specific ability (item). The sum of the individual scores from each item originate the total NIHSS score, where: 0 = no stroke symptoms; 1-4 = minor stroke; 5-15 = moderate stroke; 16-20 = moderate to severe stroke; and 21-42 = severe stroke.
Time frame: At baseline, defined as the ischaemic stroke hospital admission date, between June 2015 and December 2021
Population: Propensity score matched population based on the variables: age, sex, pre-stroke Modified Rankin Scale score, baseline National Institute of Health Stroke Scale, systolic blood pressure, glucose level, anti-platelet treatment at stroke onset, hypertension, diabetes, atrial fibrillation, hyperlipidaemia, smoking, previous stroke earlier than 3 months, stroke onset to intravenous thrombolysis treatment start time. Participants with missing values were excluded from the analysis of this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Actilyse® (Alteplase) Pre-approval | Stroke Severity, Defined by the National Institute of Health's Stroke Scale (NIHSS) | 10.5 Units on a scale |
| Actilyse® (Alteplase) Post-approval | Stroke Severity, Defined by the National Institute of Health's Stroke Scale (NIHSS) | 11 Units on a scale |
p-value: 0.91695% CI: [-0.096, 0.128]Wilcoxon (Mann-Whitney)
Secondary
Time From Onset of Symptoms to Door (or Captured in the Registry Arrival at the Hospital)
Time in minutes from the onset of ischaemic stroke symptoms to hospital door or the registry arrival at the hospital.
Time frame: Up to 4.5 hours after stroke onset, between June 2015 and December 2021
Population: Propensity score matched population based on the variables: age, sex, pre-stroke Modified Rankin Scale score, baseline National Institute of Health Stroke Scale, systolic blood pressure, glucose level, anti-platelet treatment at stroke onset, hypertension, diabetes, atrial fibrillation, hyperlipidaemia, smoking, previous stroke earlier than 3 months, stroke onset to intravenous thrombolysis treatment start time.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Actilyse® (Alteplase) Pre-approval | Time From Onset of Symptoms to Door (or Captured in the Registry Arrival at the Hospital) | 93 Minutes |
| Actilyse® (Alteplase) Post-approval | Time From Onset of Symptoms to Door (or Captured in the Registry Arrival at the Hospital) | 88 Minutes |
p-value: 0.17995% CI: [-0.199, 0.03]Wilcoxon (Mann-Whitney)
Secondary
Time From Onset of Symptoms to Start of Intravenous Thrombolysis (IVT) Treatment
Time in minutes from the onset of ischaemic stroke symptoms to start of treatment with intravenous thrombolysis with Actilyse® (alteplase).
Time frame: Up to 4.5 hours after stroke onset, between June 2015 and December 2021
Population: Propensity score matched population based on the variables: age, sex, pre-stroke Modified Rankin Scale score, baseline National Institute of Health Stroke Scale, systolic blood pressure, glucose level, anti-platelet treatment at stroke onset, hypertension, diabetes, atrial fibrillation, hyperlipidaemia, smoking, previous stroke earlier than 3 months, stroke onset to intravenous thrombolysis treatment start time.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Actilyse® (Alteplase) Pre-approval | Time From Onset of Symptoms to Start of Intravenous Thrombolysis (IVT) Treatment | 153 Minutes |
| Actilyse® (Alteplase) Post-approval | Time From Onset of Symptoms to Start of Intravenous Thrombolysis (IVT) Treatment | 151 Minutes |
p-value: 0.8195% CI: [-0.133, 0.091]Wilcoxon (Mann-Whitney)