title: Resolution of intraventricular hemorrhage varies by ventricular region and dose of intraventricular thrombolytic: the Clot Lysis: Evaluating Accelerated Resolution of IVH (CLEAR IVH) program.
abstract: OBJECTIVE
  The Clot Lysis: Evaluating Accelerated Resolution of IVH (CLEAR IVH) program is assessing the efficacy of intraventricular recombinant tissue-type plasminogen activator (rtPA) for spontaneous intraventricular hemorrhage (IVH). This subanalysis assesses the effect of dose of rtPA by region on clearance of IVH.
  
  
  METHODS
  Sixty-four patients within 12 to 24 hours of spontaneous IVH were randomized to placebo or 0.3 mg, 1 mg, or 3 mg of rtPA twice daily through an extraventricular drain. Twelve subregions of the ventricles were scored from 0 to 4. Effect of dose on IVH clearance to 50% of baseline score was compared by survival analysis for all regions combined and by subregion. Models including ventricular region, dose, and baseline score were compared by Cox proportional hazards.
  
  
  RESULTS
  IVH score reduced faster across all regions with increasing rtPA dose (clearance to 50%: log-rank P<0.0001; placebo-11.43 days, 95% CI, 5.68-17.18; 0.3 mg-3.19 days, 1.00-5.38; 1 mg-3.54 days, 0.45-6.64; 3 mg-2.59 days, 1.72-3.46). In the combined models, dose and baseline score were independently associated with reduction in IVH score, which was quickest in the midline ventricles, then the anterior half of the lateral ventricles and slowest in the posterior half of the lateral ventricles (clearance to 50%: P<0.0001; rtPA dose: hazard ratio, 1.47, 1.30-1.67; midline versus anterolateral hazard ratio, 1.71, 1.08-2.71; midline versus posterolateral hazard ratio, 4.05, 2.46-6.65; baseline score hazard ratio, 0.96, 0.91-1.01) with a significant interaction between dose and ventricular region (P=0.005).
  
  
  CONCLUSIONS
  rtPA accelerates resolution of IVH. This effect is dose-dependent, is greatest in the midline ventricles, and least in the posterolateral ventricles.
authors.affiliation: Department of Clinical Neurosciences, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA.
authors.forename: Alastair J S
authors.initials: AJ
authors.lastname: Webb
authors.forename: Natalie L
authors.initials: NL
authors.lastname: Ullman
authors.forename: Sarah
authors.initials: S
authors.lastname: Mann
authors.forename: John
authors.initials: J
authors.lastname: Muschelli
authors.forename: Issam A
authors.initials: IA
authors.lastname: Awad
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Hanley
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage*; D006801:Humans; D020547:Lateral Ventricles / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D015912:Thrombolytic Therapy / Q000379:methods*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage*
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator