Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12611001053910
Ethics application status
Approved
Date submitted
5/10/2011
Date registered
7/10/2011
Date last updated
29/07/2012
Type of registration
Prospectively registered

Titles & IDs
Public title
The West Australian Intravenous Minocycline and tissue plasminogen activator (TPA) Stroke Study (WAIMATSS)
Scientific title
A multi-centre, prospective, randomised pilot study of intravenous minocycline, 200mg 12 hourly for 5 doses, compared with standard care, in patients with ischaemic stroke treated with intravenous tissue plasminogen activator (tPA).
A strategy to reduce haemorrhagic transformation
Secondary ID [1] 273169 0
Nil known
Universal Trial Number (UTN)
Trial acronym
WAIMATSS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ischaemic stroke 278920 0
Condition category
Condition code
Stroke 279101 279101 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
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.
Intervention code [1] 269500 0
Treatment: Drugs
Comparator / control treatment
Intarvenous tPA alone.
Control group
Active

Outcomes
Primary outcome [1] 279740 0
The presence of any ICH on the routine follow up CT brain scan, performed 24 (plus or minus 8 hours) post treatment with tPA.
Timepoint [1] 279740 0
24 hours (plus or minus 8 hours)
Secondary outcome [1] 294342 0
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.
Timepoint [1] 294342 0
During hopsital admission
Secondary outcome [2] 294343 0
Symptomatic ICH with worsening by 4 or more points on the NIHSS score, during the hospital admission.
Timepoint [2] 294343 0
During hopsital admission
Secondary outcome [3] 294344 0
National Institute of Health Stroke Score (NIHSS)
Timepoint [3] 294344 0
Day one
Secondary outcome [4] 294345 0
National Institute of Health Stroke Score (NIHSS)
Timepoint [4] 294345 0
Day seven
Secondary outcome [5] 294346 0
Modified Rankin score and Barthel index by blinded telephone interview at days 30.
Timepoint [5] 294346 0
Day 30
Secondary outcome [6] 294347 0
Modified Rankin score and Barthel index by blinded telephone interview at days 90.
Timepoint [6] 294347 0
Day 90
Secondary outcome [7] 294348 0
MRI substudy. Presence of any subacute ICH, as defined by the presence of low attenuating lesions seen on the T2* gradient echo sequence. .
Timepoint [7] 294348 0
Days 5-7. (one single MRI to be performed during this time window)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Simple randomisation to either treatment arm will be alloacted using a randomisation table from a stastic book; sealed envelopes containing the randomisation will be included in CRF packs to be opened sequentially.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Once informed consent is obtained, a sealed envelope containing treatment allocation to either IV minocycline or standard care (ie no minocycline) will be opened. These sealed envelopes will be kept with the “Stroke kit” that is used at each of the teaching hospitals, and used by clinicians from the stroke units. Batches of 30 envelopes with equal numbers of randomly assigned
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
The primary endpoint is radiological, with assessments being performed by neuroradiologists blind to treatment allocation.
Phase
Phase 1 / Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/11/2011
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 269984 0
Other Collaborative groups
Name [1] 269984 0
West Australian Institute for Medical Research
Country [1] 269984 0
Australia
Primary sponsor type
Hospital
Name
Sir Charles Gairdner Hospital
Address
Sir Charles Gairdner Hospital
Hospital Avenue
NEDLANDS WA 6009
Country
Australia
Secondary sponsor category [1] 268973 0
None
Name [1] 268973 0
Address [1] 268973 0
Country [1] 268973 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 271950 0
Sir Charles Gairdner Hospital
Ethics committee address [1] 271950 0
4th Floor A-Block
Sir Charles Gairdner Hospital
Hospital Avenue NEDLANDS WA 6009
Ethics committee country [1] 271950 0
Australia
Date submitted for ethics approval [1] 271950 0
Approval date [1] 271950 0
17/08/2011
Ethics approval number [1] 271950 0
2011-011

Summary
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.
Trial website
Nil
Trial related presentations / publications
The West Australian Intravenous Minocycline and TPA STroke Study (WAIMATSS): A multi-centre, prospective, randomised pilot study of intravenous minocycline, 200mg 12 hourly for 5 doeses compared with standard care, in patients with ischaemic stroke tretaed with intravenous tPA. Blacker D, Prentice D, Alvaro A, Bates T, Bynevelt M, Hankey G, Kelly A, Beer C, Kohler E. International Journal of Stroke 2011;Vol 6, 38- Poster presentation at the annual scientific meeting of the Stroke Society of Australasia, Sept 2011.
Public notes

Contacts
Principal investigator
Name 33239 0
Address 33239 0
Country 33239 0
Phone 33239 0
Fax 33239 0
Email 33239 0
Contact person for public queries
Name 16486 0
David Blacker
Address 16486 0
C/O Dept of Neurology
Sir Charles Gairdner Hospital
Hospital Avenue
NEDLANDS WA 6009
Country 16486 0
Australia
Phone 16486 0
+ 61 89346 3333
Fax 16486 0
+ 61 89346 2455
Email 16486 0
[email protected]
Contact person for scientific queries
Name 7414 0
David Blacker
Address 7414 0
C/O Dept of Neurology
Sir Charles Gairdner Hospital
Hospital Avenue
NEDLANDS WA 6009
Country 7414 0
Australia
Phone 7414 0
+61 89346 3333
Fax 7414 0
+ 61 89346 2455
Email 7414 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseNeuroprotective effects of adjunctive treatments for acute stroke thrombolysis: a review of clinical evidence.2017https://dx.doi.org/10.1080/00207454.2017.1286338
Dimensions AIReducing Haemorrhagic Transformation after Thrombolysis for Stroke: A Strategy Utilising Minocycline2013https://doi.org/10.1155/2013/362961
N.B. These documents automatically identified may not have been verified by the study sponsor.