ARTSS-2: A pilot, phase IIb, randomised, multicentre, safety and activity trial of Argatroban in combination with TPA (Alteplase) Stroke Study
- Conditions
- Stroke, not specified as haemorrhage or infarctionStrokeCirculatory System
- Registration Number
- ISRCTN51505768
- Lead Sponsor
- The University of Texas Health Science Center at Houston (USA)
- Brief Summary
2015 results in: https://www.ncbi.nlm.nih.gov/pubmed/26278031
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- All
- Target Recruitment
- 50
1. Disabling ischemic stroke symptoms with onset < 3 hours treated with IV rtPA (alteplase) by local standards*.
* or <= 4.5 hours according to local standard of care
2. Age >= 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
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 <50 mg/dL (2.7 mmol/L)
20. History of primary or metastatic brain tumor
21. Current platelet count < 100,000/mm3
22. Life expectancy < 3 months
23.Patients who, in the judgment of the investigator, needs to be on concomitant (i.e., during the Argatroban infusion) anticoagulants other than Argatroban, including any form of heparin, unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), defibrinogenating agent, dextran, other direct thrombin inhibitors or thrombolytic agents, GPIIb/IIIa inhibitor or warfarin. [*Caveat: However, if in the judgment of the investigator a patient needs to be anticoagulated, but this can be deferred for 48 hours, then they could be included.]
24. Currently participating or has participated in any investigational drug or device study within 30 days before the first dose of study medication
25. Known hypersensitivity to Argatroban or its agents
26. Additional exclusion criteria if patient presents between 34.5 hours:
26.1. Age >80
26.2. Currently taking oral anticoagulants (regardless of INR)
26.3. A history of stroke and diabetes.
26.4. NIHSS > 25
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method <br> 1. Safety as measured by the incidence of:<br> 1.1. Symptomatic intracranial haemorrhage (sICH)<br> 1.2. Parenchymal Haemorrhage 2 (PH-2)<br> 1.3. Major systemic haemorrhage.<br> 2. Rates and completeness of arterial recanalisation assessed at baseline and 2-3 hours by CT-Angiogram (CTA)<br> 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<br> 4. Quality of Life obtained by standard gamble, time-trade-off method and visual analogue scale (VAS)<br> 5. Cost and cost-effectiveness analysis<br> 5.1 Medical costs associated with each treatment<br> 5.2 Incremental cost-effectiveness ratio (change in cost divided by quality of life gained)<br>