TEMPO-1 TNK- T PA EVALUATION FOR MINOR ISCHEMIC STROKE WITH PROVEN - - PowerPoint PPT Presentation

TEMPO-1 TNK-TPA EVALUATION FOR MINOR

ISCHEMIC STROKE WITH PROVEN OCCLUSION

Selecting Patients

• The principles of patient selection are based upon the

broad criteria of:

– TIA or minor stroke presentation with a diagnosis of an ischemic stroke syndrome – Minor initial symptoms that would not normally warrant use of thrombolytic medication in the judgment of the treating neurologist. – Imaging proof of an intracranial occlusion relevant to the presenting symptoms

• No region of well-defined hypodensity on the NCCT consistent with

the presenting symptoms or consistent with the suspected pathophysiology of the presenting symptoms (ie. fractured embolus to the MCA) that suggests well-evolved infarction, judged to be potentially prone to bleeding.

Selection and Enrolment of Subjects Inclusion criteria

• Acute ischemic stroke in an adult patient (18 years of age or older)
• Onset (last-seen-well) time to treatment time < 12 hours.
• Minor stroke defined as a baseline NIHSS < 6 at the time of
• randomization. Patients must have a demonstrable neurological

deficit on physical neurological examination.

• Any acute intracranial occlusion (MCA, ACA, PCA, VB territories)

defined by non-invasive acute imaging (CT angiography) that is neurologically relevant to the presenting symptoms and signs. An acute occlusion is defined as TICI 0 or TICI 1 flow.26

• Pre-stroke independent functional status in activities of daily living

with pre-stroke estimated modified Barthel Index of 90 or greater AND premorbid mRS 0 or 1.

• Informed consent from the patient or surrogate.
• Patients can be treated within 60 minutes of the CT/CTA being

completed.

Exclusion criteria

• Hyperdensity on NCCT consistent with any intracranial hemorrhage.

Any clinical suspicion of any intracranial hemorrhage even in the absence of visible blood on baseline brain imaging.

• Large acute stroke >1/3 MCA territory or ASPECTS<5 visible on

baseline CT scan.

• Core of established infarction. No area of white matter hypodensity

at a similar or lesser density to grey matter or in the judgment of the enrolling neurologist is consistent with a subacute ischemic stroke > 12 hours of age.

• Clinical history, past imaging and clinical judgment suggest that the

intracranial occlusion is chronic.

• Patient is a candidate for and should receive standard of care IV tPA.

Exclusion criteria

• Stroke occurring as an in-patient. An in-patient is a person who has

been officially admitted to the hospital to a ward bed. A patient in the ED who has not been formally admitted is still considered to be an outpatient.

• Patient has a severe or fatal or disabling illness that will prevent

improvement or follow-up or such that the treatment would not likely benefit the patient.

• Patient cannot complete follow-up due to co-morbid non-fatal

illness (such as psychiatric illness) or is visiting the host sites city and cannot return for follow-up.

• Pregnancy.
• Patient is actively taking dual antiplatelet medication (aspirin &

clopidogrel) in the last 48 hours.

• International normalized ratio ³ 1.4

Exclusion criteria

Standard thrombolysis exclusions (Taken from Canadian guidelines)

• Historical

– History of intracranial hemorrhage – Stroke or serious head or spinal trauma in the preceding three months – Recent major surgery in the preceding three months. – Arterial puncture at a non-compressible site in the previous seven days – Any other condition that could increase the risk of hemorrhage after TNK-tPA administration

Exclusion criteria

• Clinical

– Symptoms suggestive of subarachnoid hemorrhage. – Stroke symptoms due to another non-ischemic acute neurological condition such as seizure with Post-ictal Todd's paralysis or focal neurological signs due to severe hypo- or hyperglycemia. – Hypertension refractory to antihypertensive medication such that target blood pressure <185/110 cannot be achieved before treatment.

Exclusion criteria

• Laboratory

– Elevated activated partial-thromboplastin time. – Platelet count below 100,000 per cubic millimeter. – Active use of any standard or novel anticoagulant therapy with full anticoagulant dosing. [DVT prophylaxis dosing shall not prohibit enrolment]. Active use means that the patient has taken at least one dose of drug within 5 half-lives of the drug.

Enrolment/Informed Consent

• Subjects voluntarily confirm their willingness to participate in

the study

• Sign informed consent form, after subjects are informed of all

aspects of the study relevant to their decision to participate

• Consent process is documented by a written, signed and

dated informed consent form

• Give the subject adequate information
• Allow subject to consider all available options
• Respond to subject questions
• Ensure subject comprehends information

Informed Consent Process (cont.)

• Obtain subject’s voluntary consent to participate
• If subject is unable to sign, but can indicate verbal/non-

verbal approval, consent in the presence of a witness will be obtained

• Study allows use of signed informed consent,

verbal/nonverbal consent, or consent provided by a Legally Authorized Representative

• Signed copy of consent should be provided to the

subject, with the original remaining on file at the site

• Consent process should be adequately documented in

the site’s records

• On-going process during the time of subjects’ study

participation

Participating Sites:

• Calgary
• Ottawa
• Vancouver
• Montreal
• Other possible sites to follow

Study Drug Administration

• An estimated weight will be used to calculate a weight adjusted

dose.

• There will be 2 dose tiers at 0.1mg/kg and 0.25mg/kg. (25pts/tier)
• Advancement to the second dose tier will be dependent upon safe

completion of the 1rst dose tier and approval of the DSMB.

• Temperature Requirements for Tenecteplase: Store unreconstituted

product at 2-30° C. If not used immediately, reconstituted product in the vial at 2-8 °C and use within 8 hours.

• TNK-tPA will be stored in the 3T MRI medication cupboard.

• Nurse Coordinators will reconstitute and mix the TNK-tPA. Patients

will be enrolled between 0700-2300.

• 2 signatures will be required by the RN and Investigator to ensure

proper dosing and minimize any errors.

• TNK-tPA will be administered as a single intravenous bolus over 1-2
• minutes. Study drug must be given within 60 minutes of the CTA.
• TNK-tPA will be given in ER by the treating Investigator.

Prohibited Meds and Procedures:

• No antiplatelet agent, other antithrombotic medicines should be

given within the first 24 hours (+/- 6h) of the treatment.

• Patients should not undergo endovascular thrombectomy or

repeat thrombolysis.

• If the patient deteriorates, and the treating physician decides

to pursue endovascular thrombectomy, this is a Protocol Violation…….expect MANY FORMS!

Schedule of Assessments

Baseline 4-8 hour Day 1 Day 2 Day 5 or D/C Day 30 Day 90

Informed consent

X

History and examination

X

NIHSS

X X X X X X X

mRS

X X X X

Barthel Index

X X X X

CT head

X X

CTA COW

X X

Full Emergency Stroke Labs

X

Creatinine and CBC

X

ECG

X X

Adverse Event

X X X X X X

Study Drug

X

Site Monitoring

• It is paramount that the trial is performed in accordance with all

regulatory requirements; it is vital that No Protocol Violations

• ccur; No Protocol Waivers will be granted.
• An external independent monitor will ensure the completeness and

accuracy of information collected. There is a potential for Health Canada to perform an audit.

• This trial must be treated as a clinical trial, like all other industry
• trials. All study material will be stored and archived for 25 years.