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

Background and purpose: 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.

Trial registration: ClinicalTrials.gov NCT00650858.

Figure 1

Median time to each level of reduction in the baseline score for the midline ventricles for each drug group.

Figure 2

Cox Proportional-Hazard model of time until IVH score has reduced to ≤50% of the stability CT score, with dose, baseline score and region as independent variables.