Local Versus Systemic Thrombolysis for Acute Ischemic Stroke (SYNTHESIS)


Phase 3 Results

Eligibility Criteria

Inclusion criteria:
- Sudden focal neurological deficit attributable to a stroke
- Clearly defined time of onset, allowing initiation of intravenous treatment within 3 hours of symptoms onset and intra-arterial treatment within 6 hour of symptoms onset.
- Age between 18 and 80 years
Exclusion criteria:
- Disability preceding stroke consistent with a modified Rankin scale score of 2-4 (see glossary for Rankin scale)
- Coma at onset
- Severe stroke as assessed clinically (e.g. NIHSS>25)
- Rapidly improving neurological deficit or minor symptoms
- Seizure at onset of stroke
- Clinical presentation suggestive of a subarachnoid hemorrhage (even of CT scan is normal) or condition after subarachnoid hemorrhage from aneurysm
- Previous history of or suspected intracranial hemorrhage
- Previous history of central nervous system damage (i.e. neoplasm, aneurysm, intracranial or spinal surgery)
- Septic embolism, bacterial endocarditis, pericarditis
- Acute pancreatitis
- Arterial puncture at a non compressible site (e.g. subclavian or jugular vein puncture) or traumatic external heart massage or obstetrical delivery within the previous 10 days
- Another stroke or serious head trauma within the preceding 3 months
- Major surgery or significant trauma in past 3 month
- Urinary tract hemorrhage within the previous 21 days
- Documented ulcerative gastrointestinal disease during the last 3 months, esophageal varices, arterial-aneurysm, arterial/venous malformations • Neoplasm with increased bleeding risk
- Severe liver disease, including hepatic failure, cirrhosis, portal hypertension (esophageal varices) and active hepatitis
- Current therapy with intravenous or subcutaneous heparin or oral anticoagulants (e.g. warfarin sodium) to rise the clotting time
- Known hereditary or acquired hemorrhagic diathesis, baseline INR greater than 1.5, aPTT more than 1.5 times normal, or baseline platelet count less than 100,000 per cubic millimeter
- Baseline blood glucose concentrations below 50 mg per deciliter (2.75 mm/L) or above 400 mg per deciliter
- Hemorrhagic retinopathy, e.g. in diabetes (vision disturbances may indicate hemorrhagic retinopathy)
- Any history of prior stroke and concomitant diabetes
- Prior stroke within the last 3 months
- Known contrast sensitivity
- Severe uncontrolled hypertension defined by a blood pressure ≥ 185 mmHg systolic or diastolic ≥ 110 mm Hg in 3 separate occasions at least 10 minutes apart or requiring continuous IV therapy
- Prognosis very poor regardless of therapy; likely to be dead within months.
- Unlikely to be available for follow-up (e.g., no fixed home address, visitor from overseas).Any other condition which local investigators feels would pose a significant hazard in terms of risk/benefit to the patient, or if therapies are impracticable.
Computed tomographic (CT) scan exclusion criteria
- Intracranial tumors except small meningioma
- Hemorrhage of any degree
- Acute infarction (since this may be an indicator that the time of onset is uncorrected