This study looks at whether stroke patients who take FXa inhibitors (a type of blood thinner) can safely receive clot-busting treatment (IVT). IVT is a common emergency treatment for stroke, but current guidelines say it should not be given to people who have taken FXa inhibitors in the last 48 hours. This is because doctors worry that IVT might cause dangerous bleeding in the brain.
However, new research suggests that IVT might be safe for these patients. Some studies even show that stroke patients on FXa inhibitors who receive IVT do not have a higher risk of brain bleeding than other stroke patients. But because these studies were not designed as full medical trials, doctors still avoid IVT for this group.
The SIFT trial will compare two groups of stroke patients who take FXa inhibitors:
One group will receive IVT to see if it helps them recover better. One group will not receive IVT, which is the current standard. Doctors will check if IVT helps with recovery and if it causes any serious bleeding. If IVT is found to be safe and effective, this study could change stroke treatment guidelines and help more patients get life-saving care.
Right now, some guidelines say that stroke patients on FXa inhibitors should have a blood test before getting IVT, to measure how much of the drug is in their system. But these tests are not available in most hospitals, and waiting for results could delay important treatment. The SIFT trial will not require this test before giving IVT.
More and more people use FXa inhibitors to prevent strokes, but right now, they are being denied IVT based on old rules. If this study proves that IVT is safe for them, it could help doctors give better care to thousands of stroke patients.
Participant must be 18 years of age or older.
Ingestion of FXa inhibitors within the last 48 hours of symptom onset (or ongoing prescription of FXa inhibitor if unknown)
Clinical diagnosis of AIS with disabling neurological deficit
Presenting within 4.5 h of symptom onset or after awakening with symptoms of AIS with FLAIR-DWI mismatch on MRI as judged by the (neuro-) radiologist.
Endovascular treatment eligible patients with isolated large vessel occlusion of the intracranial internal carotid artery (ICA), the M1 segment of the middle cerebral artery (MCA), or both confirmed by CT or MR angiography and expected time from randomization to groin puncture of <30 minutes.
Systolic BP >185 mmHg or diastolic BP >110 mmHg despite antihypertensive treatment.
Known bleeding diathesis; manifest or recent severe bleeding; significant bleeding disorder last 6 months.
Arterial puncture at a non-compressible site; biopsy or lumbar puncture <7 days; major surgery, traumatic external heart massage, obstetrical delivery or serious trauma <14 days; history of intracranial haemorrhage; stroke <2 months, CNS neurosurgery <2 months; serious head trauma <2 months; pericarditis; sepsis; bacterial endocarditis; pericarditis; acute pancreatitis; neoplasm with increased bleeding risk; any serious medical illness likely to interact with treatment (i.e. aortic dissection); confounding pre-existent neurological or psychiatric disease.
Parallel
thrombolysis therapy
DrugAll treatment and monitoring routines are according to the hospitals' standard operating procedures (SOP), and both drugs (Alteplase (ALP) and Tenecteplase (TNK)) are approved drugs for the indication AIS with similar efficacy and safety profile. SIFT is designed to test the hypothesis that intravenous thrombolysis (IVT) (tenecteplase 0.25 mg/kg or alteplase 0.9 mg/kg intravenously) is efficient and safe in acute ischemic stroke patients (AIS) with recent ingestion (last 48 hours) of an Factor Xa (FXa) inhibitor who otherwise are eligible for IVT.
Early neurological improvement (ENI)
Early neurological improvement, defined as a reduction of ≥8 points on the National Institutes of Health Stroke Scale (NIHSS), or NIHSS of 0-1 at 24 hours (22-36 h).
NIHSS change
Percentage change in NIHSS (National Institutes of Health Stroke Scale) from baseline to 24 hours (22-36 hours). To compare clinical neurological improvement between patients treated with IVT and patients treated with the current standard of care. The National Institutes of Health Stroke Scale (NIHSS) consists of 11 items, each assessing a distinct neurological function, with scores ranging from 0 to 4. A score of 0 typically reflects normal function for the given domain, while higher scores indicate varying degrees of impairment. The total NIHSS score is derived by summing the individual item scores, with the total score representing the overall severity of neurological deficit. The scale's total score ranges from 0 to 42, where 0 indicates no neurological impairment, and 42 signifies the most severe impairment.
Infarct volume
Percent change in infarct volume at 24 hours ± 12 hours. To compare infarct volume on CT/MRI (computed tomography/magnetic resonance imaging) at 24 hours ±12 hours between patients treated with intravenous thrombolysis and patients treated with the current standard of care, infarct volume is defined as follows: For magnetic resonance imaging, infarct volume is a visible hyperintense area on both T2 FLAIR (T2 Fluid-Attenuated Inversion Recovery) and diffusion-weighted imaging (DWI) with a decrease in apparent diffusion coefficient (ADC). For computed tomography, infarct volume involves manual delineation of the hypodense infarct area.
mRS (modified Rankin Scale) score
Obtaining a good functional outcome (mRS 0-2) at day 90 (+/- 2weeks); obtaining an excellent functional outcome (mRS 0-1) at day 90 (+/- 2 weeks); mRS category at day 90 (+/- 2 weeks). To compare functional outcome between patients treated with IVT and patients treated with the current standard of care. The Modified Rankin Scale (MRS) assesses the degree of disability or dependence in daily activities following a stroke or other neurological event. It ranges from 0, indicating no symptoms, to 6, indicating death. The scale measures levels of disability from no impairment (0) to severe disability requiring constant care (5), with intermediate levels reflecting varying degrees of functional limitation and need for assistance.
Symptomatic Intracranial Hemorrhage (sICH)
Occurrence of sICH on CT/MRI within 36 hours post IVT causally related to an increase of 4 points or more on the NIHSS. To compare the rate of sICH in AIS patient with ingestion of FXa inhibitors within the last 48 hours and treated with IVT within 4.5 hours after stroke onset versus the expected sICH rate seen in Norway in patients not taking FXa inhibitors prior to IVT.
Click on the lead sponsor to view all of their trials.
Guri Hagberg
Lead sponsor
Oslo University Hospital
Sponsor institution
Klinbeforsk
Collaborator
Clinical Trial Unit (CTU), Oslo University Hospital
Collaborator
