Ischemic StrokePhase 2AASISTNCT02150785
Asia Africa Streptokinase Trial
A Phase 2 study testing Streptokinase in people with Ischemic Stroke, run by University of Alberta.
Trial summary
Currently, thrombolysis is offered to less than 1% of patients in low to middle income countries (LMICs) where access to health care is often based on the financial capabilities of the patient. There is therefore an urgent need for an effective but affordable alternative thrombolytic agent. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- Streptokinase
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jun 2014to Sep 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All patients included in the study will have
- acute ischemic stroke within 3 hours of symptom onset. In cases where onset time can not be established including symptoms upon waking, it will be considered to be the time when the patient was last known to be well
- Baseline NIHSS must be 4-22 inclusive
- Blood pressure (BP) must be ≤180 mmHg systolic and ≤105 mmHg diastolic at the time of enrolment. Treatment of higher systolic BP is permitted, prior to enrolment -Female patients of child-bearing potential will have a negative pregnancy test prior to enrolment
- All patients will have no evidence of acute ischemic changes on non-contrast CT (NCCT) scan at the time of enrolment
Who cannot join
- Patients with focal neurological deficits due to other cerebral pathology, such as intracerebral hemorrhage or neoplasm will be excluded
- Patients with rapidly resolving symptoms will be excluded, as will those with pre-existing functional deficits (mRS>2) or any history of intracranial bleeding. Recent (<3 months) surgical or ACS patients will be excluded Patients with known secured or unsecured cerebral aneurysms or arteriovenous malformations will not be eligible. Patients previously treated with SK will be ineligible due to the possibility of allergic reaction. Patients with known coagulopathies or platelet counts <100 000/μl will be excluded. Exclusion criteria specific and critical to this study are:
- Onset >3 hours prior to treatment. Although thrombolysis has been shown to be effective up to 4.5 hours after onset6, the number needed to treat rises exponentially after 3 hours. The greatest opportunity for successful treatment therefore is in patients treated within 3 hours
- Any areas of hypoattenuation on NCCT. Although patients with early ischemic changes that are limited in distribution may still benefit from thrombolysis, the optimal responders have no evidence of early infarction
- Patients with systolic BP >180 mmHg prior to randomization will be excluded. If BP can be controlled with IV antihypertensives (maximum 2 doses), they may be enrolled. This is more conservative than current thrombolysis guidelines, which permit initiation of therapy if systolic BP is <185 mmHg. This is based on previous data indicating the impact of elevated BP on hemorrhagic risk
- Patients treated with anticoagulants (warfarin/heparin/direct thrombin inhibitors/factor Xa antagonists) will be excluded, irrespective of INR or PTT. Although AHA guidelines allow treatment of patients on warfarin to be treated if INR is <1.5 (or heparin, if it is stopped and PTT is <50 s), these patients are at increased risk of hemorrhagic transformation. In addition, patients taking ASA/clopidogrel or ASA/dipyridamole combinations will be excluded Patients taking monotherapy antiplatelet agents will be eligible
- Blood glucose >11.1 mmol/L. Hyperglycemia has been shown to be associated with poor response to thrombolysis and also to increased risk of hemorrhagic transformation Therefore, although patients with blood glucose <18 mmol/L are normally eligible for tPA, they will be excluded
About this study
Official title: The Effectiveness of Administering Streptokinase as a Thrombolytic Agent in the Management of Acute Stroke
Currently, thrombolysis is offered to less than 1% of patients in low to middle income countries (LMICs) where access to health care is often based on the financial capabilities of the patient. There is therefore an urgent need for an effective but affordable alternative thrombolytic agent. Streptokinase (SK) ($35) is much more economically feasible as opposed to tissue plasminogen activator (tPA) ($2800). In this study, we propose a reevaluation of the use of streptokinase (SK) in the treatment of acute ischemic stroke. We want to emphasize that we will only consider this as a 'treatment option' if we are absolutely certain that IV tissue plasminogen activator (tPA) will not be offered to the patient due to its high cost. It is hypothesized that treatment with SK in appropriately selected patients will be associated with a hemorrhagic transformation rate similar to that of tPA.
Read the detailed description
Study design: The AASIST study is planned as an open label feasibility and safety study of acute treatment with SK (15 000 units/Kg) in ischemic stroke patients within 3 hours of onset.
Overall Aims and Hypotheses: The primary study aim is to demonstrate the feasibility and safety of SK based thrombolysis in ischemic stroke patients presenting less than 3 hours after symptom onset. It is hypothesized that treatment with SK (15 000 units/kg) in appropriately selected patients will be associated with a hemorrhagic transformation rate similar to that of tPA.
The goal of our proposal is to establish a safe and effective treatment for ischemic stroke patients who are candidates for thrombolysis, but are currently NOT being treated with tissue plasminogen activator (tPA) due to cost constraints. Streptokinase (SK) is an established thrombolytic that is widely available and is currently used as first line therapy for acute coronary syndromes in low/middle income countries (LMIC). SK is much more economically feasible in the developing world (≈$35 vs ≈$2800 for tr-PA). Previous studies of SK in acute stroke indicate that the risk of hemorrhagic complications is significant. It is our hypothesis, however, that the higher rates of hemorrhagic complications seen in these trials were due to other aspects of trial design, rather than the drug itself. These factors include a prolonged treatment window (up to 6 hours from symptom onset), the dose of SK and the concomitant use of antithrombotic medications. In addition, patients who are now recognized to be poor thrombolysis candidates were included in these trials, including those with excessively high arterial pressures, drowsiness prior to treatment and established early infarct changes on non-contrast CT.
In the last two decades, extensive experience with acute stroke thrombolysis has led to improved patient selection and better recognition of factors associated with increased risk of complications, in particular intracerebral hemorrhage. We believe a fresh look at SK is warranted because of the immense burden of disease, especially in LMICs. If we are able to show that SK has safety comparable to tPA and if further research on efficacy is also positive, we will be in a position to offer effective thrombolysis to a wider population at risk in LMICs.
The primary endpoint of this study is the rate of hemorrhagic transformation. Secondary safety endpoints include systemic bleeding complications and the development of hypotension. The DSMB will be closely involved in this initial phase and all case report forms and imaging studies will be submitted to the committee. We have also established a priori study stopping rules, based on hemorrhagic transformation rates. Once it can be established that SK is safe when used in the context of this protocol, a larger phase III randomized controlled trial is planned, aimed at demonstrating clinical efficacy. Data from this pilot study will be used to refine the treatment protocol and in power calculations for the required sample size of the next phase of the program.
This study will also provide an opportunity to link 20-30 emerging stroke centers in LMICs (India, Pakistan, Sudan) with high-income country (HIC) sites. Establishing this network will facilitate future clinical research studies as well, by establishing a framework for further research collaboration and exchange of personnel between LMIC and HIC sites.
- Conditions
- Ischemic Stroke
- Being tested
- Streptokinase
- Keywords
- Thrombolysis, Safety of Streptokinase, tissue plasminogen activator tPA, Stroke treatment
- Medical subject headings
- Ischemic Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
StreptokinaseDrug
| Study group | Role | What they receive |
|---|---|---|
| Adminstering Streptokinase | Experimental | treatment with 15,000 units/Kg of streptokinase in ischemic stroke patients with symptoms onset for less than 3 hours Receives: Drug: Streptokinase |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess and measure the safety and efficacy of streptokinase (15 000 units/kg) as a successful and appropriate thrombolytic agent for ischemic stroke patients of low/middle income countries who can not afford the costly tissue plasminogen (tPA).
For safety, we will evaluate the presence of blood on CT scans done within 24 hours of the recruitment . Both asymptomatic and symptomatic hemorrhages will be recorded. For efficacy, the ninety day modified Rakin scale will be used.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2014 (estimated)
- Study startJun 2014
- Primary completionJun 2016 (estimated)
- Study completionSep 2016 (estimated)
Why it stopped: Could not get study started.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- More trials run by University of AlbertaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ashfaq Shuaib, MD, FRCPC, Principal investigator, University of Alberta
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02150785
- Sponsor's protocol ID
- AASIST
- Acronym
- AASIST
- Status last verified
- May 2022
- First submitted
- 20 May 2014
- Last updated
- 27 May 2022
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 27 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effectiveness of Administering Streptokinase as a Thrombolytic Agent in the Management of Acute Stroke
- ClinicalTrials.gov ID
- NCT02150785
- Acronym / sponsor ID
- AASIST / AASIST
- Conditions
- Ischemic Stroke
- Keywords
- Thrombolysis, Safety of Streptokinase, tissue plasminogen activator tPA, Stroke treatment
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Could not get study started.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of AlbertaUniversity, hospital or other
- Study start
- Jun 2014
- Primary completion
- Jun 2016 (estimated)
- Study completion
- Sep 2016 (estimated)
- First posted
- 30 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Currently, thrombolysis is offered to less than 1% of patients in low to middle income countries (LMICs) where access to health care is often based on the financial capabilities of the patient. There is therefore an urgent need for an effective but affordable alternative thrombolytic agent. Streptokinase (SK) ($35) is much more economically feasible as opposed to tissue plasminogen activator (tPA) ($2800). In this study, we propose a reevaluation of the use of streptokinase (SK) in the treatment of acute ischemic stroke. We want to emphasize that we will only consider this as a 'treatment option' if we are absolutely certain that IV tissue plasminogen activator (tPA) will not be offered to the patient due to its high cost. It is hypothesized that treatment with SK in appropriately selected patients will be associated with a hemorrhagic transformation rate similar to that of tPA.
Detailed description
Study design: The AASIST study is planned as an open label feasibility and safety study of acute treatment with SK (15 000 units/Kg) in ischemic stroke patients within 3 hours of onset.
Overall Aims and Hypotheses: The primary study aim is to demonstrate the feasibility and safety of SK based thrombolysis in ischemic stroke patients presenting less than 3 hours after symptom onset. It is hypothesized that treatment with SK (15 000 units/kg) in appropriately selected patients will be associated with a hemorrhagic transformation rate similar to that of tPA.
The goal of our proposal is to establish a safe and effective treatment for ischemic stroke patients who are candidates for thrombolysis, but are currently NOT being treated with tissue plasminogen activator (tPA) due to cost constraints. Streptokinase (SK) is an established thrombolytic that is widely available and is currently used as first line therapy for acute coronary syndromes in low/middle income countries (LMIC). SK is much more economically feasible in the developing world (≈$35 vs ≈$2800 for tr-PA). Previous studies of SK in acute stroke indicate that the risk of hemorrhagic complications is significant. It is our hypothesis, however, that the higher rates of hemorrhagic complications seen in these trials were due to other aspects of trial design, rather than the drug itself. These factors include a prolonged treatment window (up to 6 hours from symptom onset), the dose of SK and the concomitant use of antithrombotic medications. In addition, patients who are now recognized to be poor thrombolysis candidates were included in these trials, including those with excessively high arterial pressures, drowsiness prior to treatment and established early infarct changes on non-contrast CT.
In the last two decades, extensive experience with acute stroke thrombolysis has led to improved patient selection and better recognition of factors associated with increased risk of complications, in particular intracerebral hemorrhage. We believe a fresh look at SK is warranted because of the immense burden of disease, especially in LMICs. If we are able to show that SK has safety comparable to tPA and if further research on efficacy is also positive, we will be in a position to offer effective thrombolysis to a wider population at risk in LMICs.
The primary endpoint of this study is the rate of hemorrhagic transformation. Secondary safety endpoints include systemic bleeding complications and the development of hypotension. The DSMB will be closely involved in this initial phase and all case report forms and imaging studies will be submitted to the committee. We have also established a priori study stopping rules, based on hemorrhagic transformation rates. Once it can be established that SK is safe when used in the context of this protocol, a larger phase III randomized controlled trial is planned, aimed at demonstrating clinical efficacy. Data from this pilot study will be used to refine the treatment protocol and in power calculations for the required sample size of the next phase of the program.
This study will also provide an opportunity to link 20-30 emerging stroke centers in LMICs (India, Pakistan, Sudan) with high-income country (HIC) sites. Establishing this network will facilitate future clinical research studies as well, by establishing a framework for further research collaboration and exchange of personnel between LMIC and HIC sites.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adminstering Streptokinase | Experimental | Drug: Streptokinasetreatment with 15,000 units/Kg of streptokinase in ischemic stroke patients with symptoms onset for less than 3 hours |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- All patients included in the study will have
- acute ischemic stroke within 3 hours of symptom onset. In cases where onset time can not be established including symptoms upon waking, it will be considered to be the time when the patient was last known to be well
- Baseline NIHSS must be 4-22 inclusive
- Blood pressure (BP) must be ≤180 mmHg systolic and ≤105 mmHg diastolic at the time of enrolment. Treatment of higher systolic BP is permitted, prior to enrolment -Female patients of child-bearing potential will have a negative pregnancy test prior to enrolment
- All patients will have no evidence of acute ischemic changes on non-contrast CT (NCCT) scan at the time of enrolment
Key exclusion criteria (7 listed)
- Patients with focal neurological deficits due to other cerebral pathology, such as intracerebral hemorrhage or neoplasm will be excluded
- Patients with rapidly resolving symptoms will be excluded, as will those with pre-existing functional deficits (mRS>2) or any history of intracranial bleeding. Recent (<3 months) surgical or ACS patients will be excluded Patients with known secured or unsecured cerebral aneurysms or arteriovenous malformations will not be eligible. Patients previously treated with SK will be ineligible due to the possibility of allergic reaction. Patients with known coagulopathies or platelet counts <100 000/μl will be excluded. Exclusion criteria specific and critical to this study are:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Streptokinase | Drug | Adminstering Streptokinase |
Primary outcome
To assess and measure the safety and efficacy of streptokinase (15 000 units/kg) as a successful and appropriate thrombolytic agent for ischemic stroke patients of low/middle income countries who can not afford the costly tissue plasminogen (tPA).
Time frame: 2 years
For safety, we will evaluate the presence of blood on CT scans done within 24 hours of the recruitment . Both asymptomatic and symptomatic hemorrhages will be recorded. For efficacy, the ninety day modified Rakin scale will be used.
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 May 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ashfaq Shuaib, MD, FRCPC principal investigator
University of Alberta
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Streptokinase in people with Ischemic Stroke, run by University of Alberta.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 27 May 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess and measure the safety and efficacy of streptokinase (15 000 units/kg) as a successful and appropriate thrombolytic agent for ischemic stroke patients of low/middle income countries who can not afford the costly tissue plasminogen (tPA). (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 May 2022.