Interventional Management of Stroke (IMS) III Trial
Condition: Stroke
MeSH terms: Stroke
Intervention: IV rt-PA alone; endovascular therapy
Intervention description: Intravenous (IV) recombinant tissue plasminogen activator (rt-PA) is the only approved acute stroke therapy; Group one will receive the standard dose of IV rt-PA given over an hour.; Group two will receive a lower dose or the standard dose of IV rt-PA and then undergo an angiogram test (cerebral angiography) right after the medicine is given to check for blood clots. If a clot is not seen then no more treatment will be given. If a clot is seen, the neurointerventionalist will then choose a protocol approved endovascular treatment given directly in the brain artery that will be most effective in reopening the blocked artery. Endovascular therapy can be implemented with or without interarterial rt-PA use.
Intervention MeSH terms: Tissue Plasminogen Activator
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 656.0
Sex: All
Minimum age: 18 Years
Maximum age: 82 Years
Healthy volunteers: No
Keywords: acute ischemic stroke; rt-PA; thrombolytic; recombinant tissue plasminogen activator; recanalization; blood clot; stroke; clot-dissolving; Activase®; Actilyse®; Concentric Merci® Retriever; EKOS® Micro-Infusion catheter (MicroLysus); The Penumbra System™; Standard microcatheter

Summary:

      The purpose of this study is to compare two different treatment approaches to recanalization
      started within 3 hours of symptom onset-combined intravenous (IV) and endovascular therapy
      and standard intravenous (IV) rt-PA alone.
    

Eligibility criteria:

        Inclusion Criteria

          -  Age: 18 through 82 years (i.e., candidates must have had their 18th birthday, but not
             had their 83rd birthday)

          -  Initiation of intravenous rt-PA within 3 hours of onset of stroke symptoms. Time of
             onset is defined as the last time when the subject was witnessed to be at baseline
             (i.e., subjects who have stroke symptoms upon awakening will be considered to have
             their onset at beginning of sleep)

          -  An NIHSSS >/= 10 at the time that intravenous rt-PA is begun or an NIHSSS >7 and <10
             with an occlusion seen in M1, ICA or basilar artery on CTA at institutions where
             baseline CTA imaging is standard of care for acute stroke patients.

          -  Investigator verification that the subject has received/ is receiving the correct IV
             rt-PA dose for the estimated weight prior to randomization

        Exclusion Criteria

          -  History of stroke in the past 3 months

          -  Previous intra-cranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arteriovenous
             malformation

          -  Clinical presentation suggests a subarachnoid hemorrhage, even if initial CT scan is
             normal

          -  Hypertension at time of treatment; systolic BP > 185 or diastolic > 110 mm Hg) or
             aggressive measures to lower BP to below these limits are needed.

          -  Presumed septic embolus, or suspicion of bacterial endocarditis

          -  Presumed pericarditis, including pericarditis after acute MI

          -  Suspicion of aortic dissection

          -  Recent (within 30 days) surgery or biopsy of parenchymal organ

          -  Recent (within 30 days) trauma, with internal injuries or ulcerative wounds

          -  Recent (within 90 days) severe head trauma or head trauma with loss of consciousness

          -  Any active or recent (within 30 days) hemorrhage

          -  Pts with known hereditary or acquired hemorrhagic diathesis, coagulation factor
             deficiency or oral anticoagulant therapy require coagulation labs results prior to
             enrollment. Any subject with INR > 1.7 or institutionally equivalent prothrombin time
             is excluded. Patients without history or suspicion of coagulopathy do not require INR
             or prothrombin time lab results to be available prior to enrollment.

          -  Females of childbearing potential who are known to be pregnant and/or lactating or who
             have positive pregnancy tests on admission

          -  Baseline lab values: glucose < 50 mg/dl or > 400 mg/dl, platelets <100,000, or Hct <25

          -  Requires hemodialysis or peritoneal dialysis, or has a contraindication to an
             angiogram for whatever reason

          -  Received heparin or a direct thrombin inhibitor (Angiomax, argatroban, Refludan,
             Pradaxa) within 48 hours must have a normal partial thromboplastin time (PTT) to be
             eligible

          -  History of an arterial puncture at a non-compressible site or a lumbar puncture in the
             previous 7 days

          -  History of seizure at onset of stroke

          -  History of a pre-existing neurological or psychiatric disease that would confound the
             neurological or functional evaluations, mRS score at baseline must be < 2. This
             excludes patients who live in a nursing home or who are not fully independent for
             activities of daily living (toileting, dressing, eating, cooking and preparing meals,
             etc.)

          -  Other serious, advanced, or terminal illness

          -  Any other condition that the investigator feels would pose a significant hazard to the
             subject if Activase (Alteplase) therapy is initiated

          -  Current participation in another research drug treatment protocol

          -  Informed consent is not or cannot be obtained.

          -  High density lesion consistent with hemorrhage of any degree on baseline imaging

          -  Significant mass effect with midline shift on baseline imaging

          -  Large (>1/3 of the middle cerebral artery) regions of clear hypodensity on the
             baseline CT scan. (ASPECTS of < 4 can be used as a guideline) Sulcal effacement and/or
             loss of grey-white differentiation are not contraindications to tx

          -  CT evidence of intrapararenchymal tumor

          -  Baseline CTA without evidence of arterial occlusion