None listed
Conditions
Brief summary
Intravenous tissue plasmingen activator (tPA), is an approved therapy for ischaemic (clotting type) of stroke. A worrisome side effect of tPA is haemorrhagic transformation; ie bleeding into damaged brain tissue. This occurs in over 6% of stroke patients treated with tPA, and is associated with a mortality rate of approximately 50%. Minocycline, is an anti-biotic with properties that may protect brain tissue in stroke. Early studies confirm its safety in stroke patients. Animal experiments combining the two agents have shown reduction s in haemorrhage. The WAIMATSS study examines this combination in humans, with the aim being to reduce haemorrhage.
Interventions
Intravenous minocycline, 200mg 12 hourly for 5 doses, in patients with ischaemic stroke treated with intravenous tissue plasminogen activator (tPA), to be commenced within 6 hours of symptom onset.
Sponsors
Sir Charles Gairdner Hospital
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used)
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Subjects must meet the standard inclusion criteria for use of intravenous tPA, be at least 18 years of age and provide informed consent.
Exclusion criteria
Standard exclusion criteria for routine use of tPA The critera for excluding use of tPA, as per the WA protocol for administration of intravenous tPA are; 1. Uncertainty about time of stroke onset (eg. patients awakening from sleep) 2. Coma or severe obtundation with fixed eye deviation and complete hemiplegia 3. Hypertension: systolic blood pressure greater than or equal to 180mmHg; or diastolic blood pressure >110mmHg on repeated measures prior to study. 4. Clinical presentation suggestive of subarachnoid haemorrhage even if the CT scan is normal 5. Presumed septic embolus 6. Patient having received a heparin medication within the last 48 hours and has elevated APTT or has a known hereditary or acquired haemorrhagic diathesis (eg. INR or APTT greater than normal). Known lupus anticoagulant is not a contraindication to alteplase. 7. INR >1.5 Known advanced liver disease, advanced right heart failure, or anticoagulation, and INR > 1.5 (no need to wait for INR result in the absence of the former three conditions) 8. Known platelet count <100,000 uL 9. Serum glucose is < 2.8mmol/l or >22.0 mmol/l Relative contra-indications; 1. Severe neurological impairment with NIHSS score >22 2. Age >80 years 3. CT evidence of extensive middle cerebral artery (MCA) territory infarction (sulcal effacement or blurring of grey-white junction in greater than 1/3 of MCA territory) 4. Stroke or serious head trauma within the past 3 months where the risks of bleeding are considered to outweigh the benefits of therapy 5. Major surgery within the last 14 days (consider intra-arterial thrombolysis) 6. Patient has known history of intracranial haemorrhage, subarachnoid haemorrhage, known intracranial arteriovenous malformation or previously known intracranial neoplasm such that, in the opinion of the clinician, the increased risk of intracranial bleeding would outweigh the potential benefits of treatment 7. Suspected recent (within 30 days) myocardial infarction 8. Recent (within 30 days) biopsy of a parenchymal organ or surgery that, in the opinion of the responsible clinician, would increase the risk of unmanageable (eg. uncontrolled by local pressure) bleeding 9. Recent (within 30 days) trauma with internal injuries or ulcerative wounds 10. Gastrointestinal or urinary tract haemorrhage within the last 30 days or any active or recent haemorrhage that, in the opinion of the responsible clinician, would increase the risk of unmanageable (eg by local pressure) bleeding 11. Arterial puncture at non-compressible site within the last 7 days 12. Concomitant serious, advanced or terminal illness or any other condition that, in the opinion of the responsible clinician would pose an unacceptable risk 13. Rapidly improving deficit 14. Seizure: If the presenting neurological deficit is deemed due to a seizure, do NOT give alteplase. If the presenting neurological deficit is related to ischaemia, consider alteplase as per protocol 15. Pregnancy is not an absolute contraindication. Consider referral for intra-arterial thrombolysis . (Pregnancy IS an exclusion criteria for WAIMATSS.) Specific exclusion criteria for the trial; 1.Evidence of other significant CNS disease that interferes with assessment (eg tumor, multiple sclerosis) 2. Known allergy to tetracyclines/intolerance of minocycline. 3. Known systemic lupus erythrematosis 4. Idiopathic intracranial hypertension. 5. Concurrent treatment with Vitamin A or retinoids. 6. Participation in another clinical drug trial. 7. Known significant renal failure, CLcr < 30mL/min by the Crockoft-Gault equation. 8. Known significantly abnormal liver function tests (ALT > x3 ULN) 9. Known thrombocytopaenia < 100 x 109/L. 10. Concurrent infection (at enrolment) requiring antibiotic treatment. 11. Pregnancy 12. Severe stroke or other co-morbidities likely to result in the patient dying within a week.
Outcome results
None listed