1. In patients with spontaneous intracerebral hemorrhage and intraventricular hemorrhage, intraventricular alteplase use was associated with a small reduction in the parenchymal intracerebral hemorrhage volume.
2. However, no association was observed between change in intracerebral hemorrhage volume and improved functional outcomes or mortality.
Evidence Rating Level: 2 (Good)
Study Rundown: The volume of intracranial blood in patients with spontaneous intracerebral hemorrhage (ICH) is one of the factors associated with poor outcomes and overall mortality. A recent randomized clinical trial, CLEAR III, found that the use of intraventricular thrombolysis reduced intraventricular hemorrhage (IVH) volume in patients with spontaneous ICH leading to decreased mortality. However, it is unclear if a similar association between intraventricular thrombolytic therapy and parenchymal ICH volume exists. This cohort study, a post hoc analysis of CLEAR III, assessed the association between intraventricular alteplase use and ICH volume, subsequently evaluating the association between a change in parenchymal ICH volume and long-term disability and functional outcomes. The primary endpoint was the change in parenchymal ICH volume between the hematoma stability and size on computed tomography imaging at the end of treatment. Secondary endpoints were a modified Rankin Scale score higher than 3 and mortality assessed at 6 months. Among 454 patients with ICH and IVH, intraventricular alteplase use was associated with a small reduction in the parenchymal ICH volume. However, there was no association between change in parenchymal ICH volume and improved functional outcomes or mortality. Thus, the authors recommend considering intraventricular thrombolysis in scenarios with moderate to large ICH with IVH. A limitation of this study was that by using data from the CLEAR III trial where only patients with small parenchymal ICH volumes were included, the generalizability of the study findings will be limited to this specific patient population.
In-Depth [prospective cohort]: This post hoc exploratory study included 454 patients (254 men [55.9%]; mean [SD] age, 59  years) with ICH and IVH from the CLEAR III trial between September 2009 to January 2015, with data analysis completed in June 2021. Among them, 230 (50.7%) patients were randomized to receive intraventricular alteplase and 224 (49.3%) to receive normal saline. Patients with primary IVH were excluded. Overall, patients who received alteplase had a greater mean (SD) reduction in parenchymal ICH volume compared to those that received saline (1.8 [0.2] mL vs 0.4 [0.1] mL; P < .001). The primary analysis found that alteplase use was associated with a change in the parenchymal ICH volume in both the unadjusted analysis per 1-mL change (β, 1.37; 95%CI, 0.92-1.81; P < .001) and multivariable linear regression analysis (β, 1.20; 95%CI, 0.79-1.62; P < .001). The secondary analyses found no association between change in parenchymal ICH volume and poor outcome (OR, 0.97; 95%CI 0.87-1.10; P = .64) or mortality (OR, 0.97; 95%CI 0.99-1.08; P = .59).
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