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Background: Thrombolytic therapy after intraventricular hemorrhage (IVH) is being used with increasing frequency in recent years, and was recently evaluated in a randomized, placebo controlled blinded prospective clinical trial (CLEAR III). Hemorrhagic complications have remained a concern with thrombolysis in hemorrhagic stroke. We herein present a root case analysis of all cases with adjudicated symptomatic rebleeding identified in the CLEAR III Trial.Methods: We reviewed safety reports on symptomatic rebleeding events encountered within one year from randomization among subjects enrolled in CLEA III trial, with prospectively articulated definitions and reporting standards. Medical and imaging data were retrieved through the trial database. We analyzed clinical presentation, baseline and follow-up imaging, laboratory abnormalities, medical and surgical management aspects that may have contributed to rebleeding. Subjects were individually analyzed and classified according to onset of (dosing period, early post-dosing and delayed) rebleeding, pattern of bleeding and treatment rendered (alteplase vs. saline), and potential factors contributing the rebleeding.Results: Twenty-one subjects developed a secondary symptomatic hemorrhage constituting 4% of subjects in the trial. Symptomatic rebleeding events took place during the dosing protocol (n=9, 6 in the alteplase group), early after the protocol (n=6, 2 in the alteplase group) and late (n=6, none in the alteplase group). Catheter-related hemorrhages were the most common (n=7, 33%) followed by intraventricular (n=6, 30%) and intracerebral hemorrhage (n=5, 25%). Rebleeding during the dosing period resulted from a combination of treatment- and patient-related factors and could be partially attributable to alteplase in 6 of 9 cases. Rebleeding after the dosing protocol was primarily dependent on patients’ risk factors.Conclusion: Overall risk of symptomatic hemorrhagic complications are low after intraventricular thrombolysis for IVH as long as safety protocols are followed as deployed in the clinical trial. Secondary prevention strategies are needed following the acute care phase to minimize rebleeds.