The West Australian Intravenous Minocycline and tissue plasminogen activator (TPA) Stroke Study (WAIMATSS)

Phase 1

Recruiting

• Conditions: Ischaemic stroke; Stroke - Ischaemic

• Registration Number: ACTRN12611001053910
• Lead Sponsor: Sir Charles Gairdner Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2011-10-07
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 50

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.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
The presence of any ICH on the routine follow up CT brain scan, performed 24 (plus or minus 8 hours) post treatment with tPA.[24 hours (plus or minus 8 hours)]

Secondary Outcome Measures

Name	Time	Method
Symptomatic ICH; any ICH temporally related to deterioration in the patients condition during the hospital admission. Assessed by clinical examination; with < 3 point change in NIHSS.[During hopsital admission];Symptomatic ICH with worsening by 4 or more points on the NIHSS score, during the hospital admission.[During hopsital admission];National Institute of Health Stroke Score (NIHSS)[Day one];National Institute of Health Stroke Score (NIHSS)[Day seven];Modified Rankin score and Barthel index by blinded telephone interview at days 30.[Day 30];Modified Rankin score and Barthel index by blinded telephone interview at days 90.[Day 90];MRI substudy. Presence of any subacute ICH, as defined by the presence of low attenuating lesions seen on the T2* gradient echo sequence. .[Days 5-7. (one single MRI to be performed during this time window)]