Thrombolysis in Pediatric Stroke (TIPS)

The National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, is looking for individuals to participate in clinical studies.  Participating in clinical trials allows you to play an active role in research on the nature and causes of many disorders of the brain and nervous system, and to possibly help physician-scientists develop future treatments.  The information below is designed to help you quickly learn about actively recruiting research studies for which you or someone you know may be eligible.

Description:

This study will determine the safest dose of intravenous tissue plasminogen activator (IV-tPA) among 3 doses for children age 2 to 17 years within 4.5 hours from onset of acute ischemic stroke.

Thrombolysis in Pediatric Stroke (TIPS) is a five-year, multi-center, international safety and dose-finding study of IV-tPA in children who have had a stroke. The study will enroll a maximum of 18-21 children age 2 to 10 years and maximum of 18-21 children age 11 to 17 years.

The objectives are to determine the safest dose of IV-tPA among three doses (0.75, 0.9, and 1.0 mg/kg) for children within 4.5 hours from onset of stroke; determine the pharmacokinetics of tPA and its inhibitor, plasminogen activator inhibitor, in these children (pharmacokinetics means how the medication works in the body); and measure the 3-month neurological outcome in children treated with IV-tPA.

Phase: 

Eligibility Criteria:

Inclusion:

1. Age 2 to 17 years
2. Clinical presentation consisting of clearly defined acute onset of neurological deficit in a pattern consistent with arterial territory ischemia
3. Clinically significant deficit as defined by a PedNIHSS score of ≥ 6 and ≤ 24 felt to be due to acute stroke that is not improving at the time of initiation of tPA administration
4. Time of symptom onset within 4.5 hours of initiation of treatment for IV tPA. Time of symptom onset is defined as time the patient was last seen awake and at neurological baseline
5. Radiological confirmation of an acute arterial ischemic stroke in one of two ways:
   • Magnetic resonance imaging (MRI) confirmation, consisting of acute infarction with restricted diffusion in an arterial territory consistent with the clinical syndrome plus magnetic resonance angiogram showing partial or complete occlusion in an intracranial artery corresponding to the infarct location, OR
   • Computed tomography (CT) and CT angiogram confirmation, consisting of normal head CT or early hypodensity in an arterial territory consistent with the clinical syndrome plus CT angiogram showing partial or complete occlusion in an intracranial artery corresponding to the infarct location
6. Baseline neuroimaging (CT or MRI) with no evidence of intracranial hemorrhage (including HI-1, HI-2, PH-1 or PH-2). If no head CT scan is done, the pre-tPA MRI must include Gradient-recalled ECHO (GRE) imaging or Susceptibility Weighted Imaging (SWI) sequences.
7. Children with seizures at or following onset of stroke may be included, as long as the clinical picture is consistent with the documented arterial occlusion

Exclusion

Safety Related criteria:

1. Patients in whom time of symptom onset is unknown.
2. Clinical presentation suggestive of subarachnoid hemorrhage (SAH), even if head CT or head MRI scan is negative for blood
3. History of prior intracranial hemorrhage
4. Known cerebral arterial venous malformation, aneurysm, or neoplasm
5. Persistent Systolic Blood Pressure > 15% above the 95th percentile for age while sitting or supine
6. Glucose < 50 mg/dl (2.78 mmol/l) or > 400 mg/dl (22.22 mmol/l)
7. Bleeding diathesis including platelets < 100,000, Prothrombin time (PT) > 15 sec (International normalized ratio (INR) > 1.4) or elevated partial thromboplastin time (PTT) > upper limits of the normal range
8. Clinical presentation consistent with acute myocardial infarction (MI) or post-MI pericarditis that requires evaluation by cardiology prior to treatment
9. Stroke, major head trauma, or intracranial surgery within the past 3 months
10. Major surgery or parenchymal biopsy within 10 days (relative contraindication)
11. Gastrointestinal or urinary bleeding within 21 days (relative contraindication)
12. Arterial puncture at noncompressible site or lumbar puncture within 7 days (relative contraindication). Patients who have had a cardiac catheterization via a compressible artery are not excluded.
13. Patient with malignancy or within 1 month of completion of treatment for cancer
14. Patients with an underlying significant bleeding disorder. Patients with a mild platelet dysfunction, mild von Willebrand Disease or other mild bleeding disorders are not excluded.

Stroke related:

1. Mild deficit (PedNIHSS < 6) at start of tPA infusion
2. Severe deficit suggesting very large territory stroke, with pre-tPA PedNIHSS > 25, regardless of the infarct volume seen on neuroimaging
3. Stroke suspected to be due to subacute bacterial endocarditis, moyamoya, sickle cell disease, meningitis, bone marrow, air or fat embolism
4. Previously diagnosed primary angiitis of the central nervous system (PACNS) or secondary central nervous system vasculitis. Focal cerebral arteriopathy (FCA) of childhood is not a contraindication.

Neuro-imaging related:

1. Intracranial hemorrhage (HI-1, HI-2, PH-1 or PH-2) on pretreatment head MRI or head CT
2. Intracranial dissection (defined as at or distal to the opthalmic artery)
3. Large infarct volume, defined by the finding of acute infarct on MRI involving 1/3 or or more of the complete middle cerebral artery territory involvement, regardless of the pre-tPA PedNIHSS score due to increased risk of ICH

Drug related:

1. Known allergy to recombinant tissue plasminogen activator
2. Patient on anticoagulation therapy must have INR ≤ 1.4
3. Patient who received heparin within 4 hours must have a PTT in normal range
4. Low molecular weight heparin (LMWH) within past 24 hours (a PTT and INR will not reflect LMWH effect)

Study Design: 

Study Locations: 

For more information:

Contact:  Catherine Amlie-Lefond, MD; telephone: 1-206-987-2078; email: Catherine.Amlielefond@Seattlechildrens.org;

Visit:  http://clinicaltrials.gov/ct2/show/NCT01591096

Last Reviewed November 9, 2012