Asia Africa Streptokinase Trial

• Status: Unknown status
• Trial end date: 2016-09-01
• Target enrollment: 0
• Participant gender: All

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. 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Alberta
• Treatments: Streptokinase

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

• 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:

1. 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

2. 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

3. 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

4. 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

5. 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