Background and Purpose Patients with intracerebral hemorrhage (ICH) and intraventricular hemorrhage (IVH) have a reported mortality of 50–80%. We evaluated a clot lytic treatment strategy for these patients in terms of mortality, ventricular infection, and bleeding safety events and for its effect on the rate of intraventricular clot lysis. Methods 48 Patients were enrolled at 14 centers and randomized to treatment with 3mg recombinant tissue plasminogen activator (rt-PA) or placebo. Demographic characteristics, severity factors, safety outcomes (mortality, infection, bleeding), and clot resolution rates were compared in the two groups. Results Severity factors, including admission GCS, ICH volume, IVH volume and blood pressure, were evenly distributed, as were adverse events except for an increased frequency of respiratory system events in the placebo-treated group. Neither ICP nor Cerebral Perfusion pressure (CPP) differed substantially between treatment groups on presentation, with EVD closure, or during the active treatment phase. Frequency of death and ventriculitis was substantially lower than expected and bleeding events remained below the pre-specified threshold: mortality (18%, rt-PA; 23%, placebo); ventriculitis (8%, rt-PA; 9%, placebo); symptomatic bleeding (23%, rt-PA; 5% placebo, which approached statistical significance (p=0.1)). The median duration of dosing was 7.5 days for rt-PA and 12 days for placebo. There was a significant beneficial effect of rt-PA on rate of clot resolution Conclusions Low-dose rt-PA for the treatment of ICH with IVH has an acceptable safety profile compared to placebo and prior historical controls. Data from a well-designed Phase III clinical trial, such as CLEAR III, will be needed to fully evaluate this treatment. Clinical Trial Registration Information Participant enrollment began prior to July 1, 2005.

In this SAH population, the majority of seizures happened before medical presentation. In-hospital seizures were rare and occurred more than 7 days postictus for patients receiving AED prophylaxis. The vast majority of putative clinical predictors did not help predict the occurrence of seizures; only the thickness of the cisternal clot was of value in predicting seizures. Patient selection for and the efficacy and timing of AED prophylaxis after SAH deserve prospective evaluation.