Stroke Circulatory System Stroke, not specified as haemorrhage or infarction
Conditions
Interventions
Three treatment arms (n=35 each) will be enrolled:
1. Low-dose Argatroban* (1.0µg/kg/min continuous infusion of Argatroban, preceded by a 100 µg/kg bolus administered over 3-5 minutes
2. High-dose Argatroban* 3.0 µg/kg/min continuous infusion of Argatroban, preceded by a 100 µg/kg bolus administered over 3-5 minutes Infusion will be titrated to achieve an aPTT of 2.25 times baselin
3. Intravenous-rt-PA alone (usual care).
*Argatroban infusions will continue for a maximum of 48 hours.
During the course of the treatment, patients will be evaluated
Sponsors
The University of Texas Health Science Center at Houston (USA)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Disabling ischemic stroke symptoms with onset = 18 3. National Institutes of Health Stroke Scale (NIHSS) >= 10* or any NIHSS with an intracranial clot should be demonstrated on neurovascular imaging (TCD or CTA) in any one of the following areas: distal ICA, MCA (M1 or M2), PCA (P1 or P2), distal vertebral or basilar artery 3.1. TCD criteria: TIBI 0, 1, 2 or 3 3.2. CTAngiogram: TIMI 0 or 1 * NIHSS = 10, demonstration of clot on neuroimaging is not necessary (i.e., enrollment can proceed with noncontrast head CT alone), but if performed, a clot must be demonstrated 4. For those patients who will undergo repeat CT Angiogram at 23 hours, estimated glomerular filtration rate (eGFR) must be >= 60 mL/min/1.73m2 5. Females of childbearing potential must have a negative serum pregnancy test prior to the administration of trial medication 6. Signed (written) informed consent by the patient or the patient?s legal representative and/or guardian
Exclusion criteria
Exclusion criteria: 1. Patients whom the treating physician is planning (or could plan) to treat with intraarterial thrombolysis or other endovascular procedures (i.e., mechanical clot retrieval) aimed at recanalisation 2. Evidence of intracranial haemorrhage (ICH) on baseline CT scan or diagnosis of a nonvascular cause of neurologic deficit 3. NIHSS Level of Consciousness score (1a) >= 2 4. Preexisting disability with mRS >= 2 5. CT scan findings of hypoattenuation of the xray signal (hypodensity) involving >= 1/3 of the MCA territory 6. Any evidence of clinically significant bleeding, or known coagulopathy 7. INR >1.5 8. Patients with an elevated activated partial thromboplastin time (aPTT) greater than the upper limit of normal 9. Patients currently, or within the previous 24 hours, on an oral direct thrombin inhibitor 10. Heparin flush required for an IV line. Line flushes with saline only. 11. Any history of intracranial haemorrhage, known arteriovenous malformation or unsecured cerebral aneurysms 12. Significant bleeding episode within the 3 weeks before study enrollment 13. Major surgery or serious trauma in last 2 weeks 14. Patients who have had an arterial puncture at a noncompressible site, biopsy of parenchymal organ, or lumbar puncture within the last 2 weeks 15. Previous stroke, myocardial infarction (MI), post myocardial infarction pericarditis, intracranial surgery, or significant head trauma within 3 months 16. Uncontrolled hypertension (SBP > 185 mmHg or DBP >110 mmHg) that does not respond to intravenous antihypertensive agents 17. Surgical intervention (any reason) anticipated within the next 48 hours 18. Known history of clinically significant hepatic dysfunction or liver disease ? including a current history of alcohol abuse 19. Abnormal blood glucose 80 26.2. Currently taking oral anticoagulants (regardless of INR) 26.3. A history of stroke and diabetes. 26.4. NIHSS > 25
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Excellent functional outcome as measured by the percentage of patients with a 0 or 1 on the modified Rankin Scale (mRS) at day 90 as assessed by study personnel blinded to treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Safety as measured by the incidence of: 1.1. Symptomatic intracranial haemorrhage (sICH) 1.2. Parenchymal Haemorrhage 2 (PH-2) 1.3. Major systemic haemorrhage. 2. Rates and completeness of arterial recanalisation assessed at baseline and 2-3 hours by CT-Angiogram (CTA) 3. Neurological deficits improvement from baseline to 2 hours, 24 hours, end of Argatroban infusion, Day 7/discharge and day 90 as measured by NIHSS 4. Quality of Life obtained by standard gamble, time-trade-off method and visual analogue scale (VAS) 5. Cost and cost-effectiveness analysis 5.1 Medical costs associated with each treatment 5.2 Incremental cost-effectiveness ratio (change in cost divided by quality of life gained) | — |
Countries
United Kingdom
Outcome results
None listed