title: A multicenter, randomized, double-blinded, placebo-controlled phase III study of Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage (CLEAR III).
abstract: BACKGROUND
  In adults, intraventricular thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) facilitates resolution of intraventricular haemorrhage (IVH), reduces intracranial pressure, decreases duration of cerebrospinal fluid diversion, and may ameliorate direct neural injury. We hypothesize that patients with small parenchymal haematoma volumes (<30 cc) and relatively large IVH causing acute obstructive hydrocephalus would have improved clinical outcomes when given injections of low-dose rtPA to accelerate lysis and evacuation of IVH compared with placebo.
  
  
  METHODS
  The Clot Lysis Evaluation of Accelerated Resolution of Intraventricular Hemorrhage III trial is an investigator-initiated, phase III, randomized, multicenter, double-blind, placebo-controlled study comparing the use of external ventricular drainage (EVD) combined with intraventricular injection of rtPA to EVD plus intraventricular injection of normal saline (placebo) for the treatment of IVH. Patients with known symptom onset within 24 h of the computed tomography scan confirmed IVH and third or fourth ventricle obstruction, with or without supratentorial intracerebral haemorrhage volume <30 cc, who require EVD are screened with a computed tomography scan at least six hours after EVD placement and, if necessary, at consecutive 12-h intervals until stabilization of any intracranial bleeding has been established. Patients who meet clinical and imaging criteria (no ongoing coagulopathy and no suspicion of aneurysm, arteriovenous malformation, or any other vascular anomaly) will be randomized to either intraventricular rtPA or placebo.
  
  
  RESULTS
  The primary outcome measure is dichotomized modified Rankin Scale 0-3 vs. 4-6 at 180 days. Clinical secondary outcomes include additional modified Rankin Scale dichotomizations at 180 days (0-4 vs. 5-6), ordinal modified Rankin Scale (0-6), mortality and safety events at 30 days, mortality at 180 days, functional status measures, type and intensity of intensive care unit management, rate and extent of ventricular blood clot removal, and quality of life measures.
authors.affiliation: Division of Neurosciences Critical Care, Department of Neurology, Johns Hopkins Hospital, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Wendy C
authors.initials: WC
authors.lastname: Ziai
authors.forename: Stanley
authors.initials: S
authors.lastname: Tuhrim
authors.forename: Karen
authors.initials: K
authors.lastname: Lane
authors.forename: Nichol
authors.initials: N
authors.lastname: McBee
authors.forename: Kennedy
authors.initials: K
authors.lastname: Lees
authors.forename: Jesse
authors.initials: J
authors.lastname: Dawson
authors.forename: Kenneth
authors.initials: K
authors.lastname: Butcher
authors.forename: Paul
authors.initials: P
authors.lastname: Vespa
authors.forename: David W
authors.initials: DW
authors.lastname: Wright
authors.forename: Penelope M
authors.initials: PM
authors.lastname: Keyl
authors.forename: A David
authors.initials: AD
authors.lastname: Mendelow
authors.forename: Carlos
authors.initials: C
authors.lastname: Kase
authors.forename: Christine
authors.initials: C
authors.lastname: Wijman
authors.forename: Marc
authors.initials: M
authors.lastname: Lapointe
authors.forename: Sayona
authors.initials: S
authors.lastname: John
authors.forename: Richard
authors.initials: R
authors.lastname: Thompson
authors.forename: Carol
authors.initials: C
authors.lastname: Thompson
authors.forename: Steven
authors.initials: S
authors.lastname: Mayo
authors.forename: Pat
authors.initials: P
authors.lastname: Reilly
authors.forename: Scott
authors.initials: S
authors.lastname: Janis
authors.forename: Issam
authors.initials: I
authors.lastname: Awad
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hanley
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000209:etiology*; D002552:Cerebral Ventricles / Q000187:drug effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D020521:Stroke / Q000150:complications*; D015912:Thrombolytic Therapy / Q000379:methods; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D015898:Tomography Scanners, X-Ray Computed; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D010959:Tissue Plasminogen Activator
keywords: intracerebral haemorrhage; protocols; randomized clinical trial; stroke; thrombolysis
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