In a small pro- spective trial, 16 patients with IVH and ICH <30 mm3 were randomized to VC or VC plus urokinase.214 Clearance of IVH was faster with urokinase. Mortality at 6 months was 14% with urokinase and 44% with VC alone (P=0.22), and there were no significant differences between groups in require- ment for permanent shunts or ventriculitis. Meta-analysis of 4 randomized and 8 observational studies of patients with IVH secondary to spontaneous ICH treated with VC (n=149) or VC with intraventricular fibrinolysis (n=167) found a sig- nificant decrease in mortality from 47% to 23% (pooled Peto OR, 0.32; 95% CI, 0.19 0.52), with the difference occurring principally in patients treated with urokinase.209 There was no difference in complications or need for permanent CSF diver- sion between subjects treated with intraventricular fibrinolytic agents andVC alone. Studies with rtPA have used various dose The largest trial of intraventricular fibrinolysis to date is the CLEAR-IVH trial (Clot Lysis: Evaluating Accelerated Resolution of IVH).184,217,218 CLEAR-IVH included 100 patients (22 placebo, 78 rtPA) with IVH attributable to spon- Overall, bacterial ventriculitis occurred in 3 patients with rtPA (4%) and 2 with placebo (9%). Patients treated with rtPA had significantly lower intracranial pressures, fewer VC obstructions that required replacement, and nonsignificantly shorter duration of VC requirement. There was symptomatic rebleeding in 9 rtPA patients (12%) and 1 patient given placebo (5%; P=0.33). Permanent CSF diversion was required in 14% of placebo and 6% of rtPA patients (P=0.27). Median 30-day modified Rankin scale score was 5 in both groups, and mortality was 19%, with no significant difference between placebo and rtPA. The phase 3 randomized CLEAR III trial is in progress. 