A randomised controlled trial of TNK-tPA versus standard of care for minor ischemic stroke with proven occlusion.

Phase 1

• Conditions: To demonstrate the efficacy of using TNK-­tPA (tenecteplase), a thrombolytic agent that is relatively novel to the treatment ischemic stroke but well-­established in the treatment of myocardial infarction, to treat minor ischemic stroke patients with proven acute symptomatic occlusions or perfusion abnormalities.; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2015-005469-22-ES
• Lead Sponsor: niversity of Calgary

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-09-09
• Last Update Posted: 22 May 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 1274

Inclusion Criteria

1. Acute ischemic stroke in an adult patient (18 years of age or older)
2. Onset (last-­seen-­well) time to treatment time = 12 hours.
3. Transient Ischemic Attack or minor stroke defined as a baseline National Institutes of Health Stroke Scale (NIHSS) = 5 at the time of randomization. Patients do not have to have persistent demonstrable neurological deficit on physical neurological examination.
4. Any acute intracranial occlusion or near occlusion (Thrombolysis in cerebral ischemia (TICI) 0 or 1) (Middle Cerebal Artery, Anterior Cerebral Artery, Posterior Cerebral Artery, Vertebrobasilar territories) defined by non-invasive acute imaging Computed Tomography Angiography (CTA) or Magnetic Resonance angiography (MRA) ) that is neurologically relevant to the presenting symptoms and signs. Multiphase Computed Tomographic Angiography (CTA) or Computed Tomography (CT) perfusion are required for this study. An acute occlusion is defined as TICI 0 or TICI 1 flow.1 Practically this can include a small amount of forward flow in the presence of a near occlusion
AND,
Delayed washout of contrast with pial vessels on multiphase CTA in a region of brain concordant
with clinical symptoms and signs OR,
Any area of focal perfusion abnormality identified using CT or MR perfusion – e.g. transit delay (Time To Peak (TTP), Mean Transit Time (MTT) or Time to Peak of the impulse response (T Max) ), in a region of brain concordant with clinical symptoms and signs.
5. Pre-­stroke independent functional status-structured Modified Rankin Scale mRS =2.
6. Informed consent from the patient or surrogate.
7. Patients can be treated within 90 minutes of the first slice of CT or MRI. Scans can be repeated
to meet this requirement; if there is no change neurologically then only a CT head need be repeated
for assessment of extent and depth of ischemia.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 425
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 849

Exclusion Criteria

1. Hyperdensity on NCCT consistent with intracranial hemorrhage.
2. Large acute stroke ASPECTS < 7 visible on baseline CT scan.
3. Core of established infarction. No large area (estimated > 10 cc) of grey matter hypodensity at
a similar density to white matter or in the judgment of the enrolling neurologist is consistent with a subacute ischemic stroke > 12 hours of age.
4. Clinical history, past imaging or clinical judgment suggest that that intracranial occlusion is chronic.
5. 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.
6. Pregnancy
7. Planned thrombolysis with IV tPA or endovascular thrombolysis/thrombectomy treatment.
8. In-­-hospital stroke unless these patients are at their baseline prior to their stroke.E.g. a patient who had a stroke during a diagnostic coronary angiogram.
9. Commonly accepted exclusions for medical thrombolytic treatment. These are commonly relative
contraindications (i.e. the final decision is at the discretion of the treating physician) but for
the purposes of TEMPO-­2 include the following:
a. International normalized ratio > 1.7 or known full anticoagulation with use of any standard or novel anticoagulant therapy with fullanticoagulant dosing. [DVT prophylaxis dosing shall not prohibit enrolment]. For LMWH or the novel anticoagulants, more than 48 hours off drug will be considered sufficient to allow trial enrollment. Dual antiplatelet therapy does not prohibit enrolment. [For patients who are known not to be taking anticoagulant therapy it is not necessary to wait for coagulation lab results (e.g. PT, PTT) prior to treatment]
b. Patients who have been acutely treated with GP2b3a inhibitors.
c. Arterial puncture at a non-­compressible site in the previous seven days
d. Clinical stroke or serious head or spinal trauma in the preceding three months that would normally preclude use of a thrombolytic agent.
e. History of intracranial hemorrhage, subarachnoid hemorrhage or other brain hemorrhage that would
normally preclude use of a thrombolytic agent.
f. Major surgery within the last 3 months at a bodily site where bleeding
could result in serious harm or death.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified