Thrombolysis in Pediatric Stroke (TIPS)

NCT01591096 | Terminated Phase 1 Results DMC

• 1 other identifier: 1R01NS065818
• Study Type: interventional
• Target: 1
• Locations: 2 countries
• Sites: 15

Brief Summary

Thrombolysis in Pediatric Stroke (TIPS) is a five-year multi-center international safety and dose-finding study of intravenous (IV) tPA in children with acute ischemic stroke (AIS) to determine the maximal safe dose of intravenous Tissue Plasminogen Activator (IV-tPA) among three doses (0.75. 0.9, 1.0 mg/kg) for children age 2-17 years within 4.5 hours from onset of acute AIS.

Conditions

Stroke

Keywords

Stroke; Childhood; Thrombolysis

Outcome Measures

Primary Outcomes (1)

• Symptomatic Intracranial Hemorrhage

  Any PH 2 OR, Any intracranial hemorrhage which is judged to be the most important cause of neurological deterioration (a minimum of change of 2 or more points on the PedNIHSS from the lowest PedNIHSS). At the time of each PedNIHSS assessment, the site PI or co-PI will review the patient's course with the care team to ensure that all changes in neurologic status, including improvements since the last assessment by the study team, are captured, OR, Any hemorrhage that results in the need for transfusion, need to discontinue study drug, surgical evacuation of hemorrhage, or death.

  36 hours

Secondary Outcomes (1)

• Pharmacokinetics of tPA

  24 hours

Study Arms (1)

Tissue plasminogen activator

EXPERIMENTAL

All patients will receive study drug.

Drug: Tissue plasminogen activator (Activase®)

Interventions

Tissue plasminogen activator (Activase®) DRUG

Investigation labeled tPA will be obtained for all sites by the Core Pharmacy as commercially available recombinant tPA (Genentech as Activase®) for IV administration. The Bayesian method of toxicity probability intervals will be used to select one of the following three dose tiers (0.75, 0.9, 1.0 mg/kg) of IV tPA. The dose escalation for the two age groups (2-10, 11-17 years) will be performed independently. The maximum dose for each tier will be reached at a weight of 90 kg.

Also known as: Genentech as Activase®

Tissue plasminogen activator

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 2 to 17 years inclusive.
• Clinical presentation consisting of clearly defined acute onset of neurological deficit in a pattern consistent with arterial territory ischemia.
• 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
• 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.
• Radiological confirmation of an acute arterial ischemic stroke in one of two ways:
• MRI confirmation, consisting of acute infarction with restricted diffusion in an arterial territory consistent with the clinical syndrome plus MRA showing partial or complete occlusion in an intracranial artery corresponding to the infarct location, OR,
• 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.
• 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.
• 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.

You may not qualify if:

• Patients in whom time of symptom onset is unknown.
• Pregnancy
• Clinical presentation suggestive of subarachnoid hemorrhage (SAH), even if head CT or head MRI scan is negative for blood.
• Patient who would decline blood transfusion if indicated
• History of prior intracranial hemorrhage
• Known cerebral arterial venous malformation, aneurysm, or neoplasm
• Persistent Systolic Blood Pressure \> 15% above the 95th percentile for age while sitting or supine
• Glucose \< 50 mg/dl (2.78 mmol/l) or \> 400 mg/dl (22.22 mmol/l)
• Bleeding diathesis including platelets \< 100,000, PT \> 15 sec (INR \> 1.4) or elevated PTT \> upper limits of the normal range.
• Clinical presentation consistent with acute myocardial infarction (MI) or post-MI pericarditis that requires evaluation by cardiology prior to treatment
• Stroke, major head trauma, or intracranial surgery within the past 3 months
• Major surgery or parenchymal biopsy within 10 days (relative contraindication)
• Gastrointestinal or urinary bleeding within 21 days (relative contraindication)
• 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.
• Patient with malignancy or within 1 month of completion of treatment for cancer

Sponsors & Collaborators

• Seattle Children's Hospital: lead
• The Hospital for Sick Children: collaborator
• Medical College of Wisconsin: collaborator
• University of Texas at Austin: collaborator
• Alberta Children's Hospital: collaborator
• McMaster University: collaborator

Study Sites (15)

Stanford University and Lucile Packard Children's Hospital at Stanford

Palo Alto, California, 94304, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15244, United States

Location

Monroe Carell Jr. Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

Location

Children's Medical Center at Dallas

Dallas, Texas, 75390-9063, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

University of Texas Medical School at Houston

Houston, Texas, 77030, United States

Location

The University of Utah and Primary Children's Medical Center

Salt Lake City, Utah, 84113, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1E2, Canada

Location

Related Publications (2)

• Rivkin MJ, deVeber G, Ichord RN, Kirton A, Chan AK, Hovinga CA, Gill JC, Szabo A, Hill MD, Scholz K, Amlie-Lefond C. Thrombolysis in pediatric stroke study. Stroke. 2015 Mar;46(3):880-5. doi: 10.1161/STROKEAHA.114.008210. Epub 2015 Jan 22. No abstract available.

  PMID: 25613306 RESULT

• Bernard TJ, Rivkin MJ, Scholz K, deVeber G, Kirton A, Gill JC, Chan AK, Hovinga CA, Ichord RN, Grotta JC, Jordan LC, Benedict S, Friedman NR, Dowling MM, Elbers J, Torres M, Sultan S, Cummings DD, Grabowski EF, McMillan HJ, Beslow LA, Amlie-Lefond C; Thrombolysis in Pediatric Stroke Study. Emergence of the primary pediatric stroke center: impact of the thrombolysis in pediatric stroke trial. Stroke. 2014 Jul;45(7):2018-23. doi: 10.1161/STROKEAHA.114.004919. Epub 2014 Jun 10.

  PMID: 24916908 RESULT

MeSH Terms

Conditions

Stroke

Interventions

Tissue Plasminogen Activator

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors

Limitations and Caveats

Early termination due to lack of participant accrual.

Results Point of Contact

• Title: Catherine Amlie-Lefond MD
• Organization: SeattleChildrens

calefond@seattlechildrens.org

206-987-2078

Study Officials

• Catherine Amlie-Lefond, MD

  Seattle Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neurology

Study Record Dates

• First Submitted: May 1, 2012
• First Posted: May 3, 2012
• Study Start: October 1, 2012
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: May 25, 2018
• Results First Posted: May 25, 2018

Record last verified: 2018-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (13); CA (2)