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-AT
• Lead Sponsor: niversity of Calgary

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-08-08
• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• 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) no
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 enrollingneurologist is consistent with a subacute ischemic stroke.
4. 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.
5. Pregnancy.
6. Planned thrombolysis with intravenous tPA or endovascular acute treatment.
7. In-hospital stroke unless these patients are at their baseline prior to the stroke.
8. Commonly accepted exclusions for medical thrombolytic treatment that potentially put the patient at an increased risk of bleeding. Country specific product monographs and stroke thrombolysis guidelines should be consulted. 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. Significant bleeding disorder either at present or within the past 6 months
b. International normalized ratio > 1.7 or known full anticoagulation with use of any standard or direct oral anticoagulant therapy with full anticoagulant dosing. [DVT prophylaxis dosing shall not prohibit enrolment]. For low molecular weight heparins (LMWH) more than 48 hours off drug will be considered sufficient to allow trial enrollment. For direct oral anticoagulants; in patients with normal renal function more than 48 hours off drug will be considered sufficient to allow trial enrollment. Patients on direct oral anticoagulants who have
any degree of renal impairment should not be enrolled in the trial unless they have not taken a dose of the drug in the last 5 days.
c. 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]
d. Prolonged cardiopulmonary resuscitation (> 2 minutes) within the past 2 weeks
e. Acute pericarditis and/or subacute bacterial endocarditis
f. Acute pancreatitis
g. Severe hepatic dysfunction, including hepatic failure, cirrhosis, portal hypertension (oesophageal
varices) and active hepatitis
h. Neoplasm with increased bleeding risk
i. Arterial aneurysm and known arterial/venous malformation
j. Patients who have been acutely treated with GP2b3a inhibitors.
k. Arterial puncture at a non-compressible site in the previous seven days
l. Clinical stroke or serious head or spinal trauma in the preceding three months that would normally
preclude use of a thrombolytic agent.
m. History of intracranial hemorrhage, subarachnoid hemorrhage or other brain hemorrhage that would
normally preclude use of a thrombolytic agent.
n. Major surgery within the last 3 months that the treating physician considers a contraindication to
thrombolytic therapy.
o. Severe hypo- (< 50 mg/dL or 2.8mmol/l )or hyperglycemia (>400 or 22.2mmol/l)
p. Hypertension refractory to anti-hypertensive medication such that target blood pressure <185/110 cannot be achieved before treatment.
q. Known platelet count below 100,000 per cubic millimeter. [Treatment should not be delayed to
wait for platelet count unless thrombocytopenia is known or suspected]
r. Gastrointestinal or genitourinary bleeding within the past 3 months that would normally pre

Study & Design

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