No CLEAR functional benefits for alteplase in intraventricular hemorrhage removal
medwireNews: Irrigation with alteplase to remove intraventricular hemorrhage in patients with intracerebral hemorrhage and a routine extraventricular drain does not substantially improve functional outcome, indicate findings from the CLEAR III trial.
Among 246 patients randomly assigned to receive up to 12 doses of alteplase irrigation, 48% had a good functional outcome at 6 months, defined as a modified Rankin Scale (mRS) score of 3 or less, but this did not differ significantly from the 45% of 245 patients who were assigned to saline boluses.
The estimated treatment effect was 3.5% after taking into account the size of intraventricular hemorrhage and thalamic location.
“On the face of the current evidence […] alteplase at the dose of 1 mg every 8 h cannot be recommended as an intervention to improve functional outcome in patients with intraventricular haemorrhage,” write Daniel Hanley (Johns Hopkins University, Baltimore, Maryland, USA) and co-researchers in The Lancet.
They note, however, that clot removal analyses suggested better odds of improved functional outcome and survival with greater clot removal. Given that the study goal of 80% clot reduction was achieved by only 33% of patients given alteplase, the team believes that the treatment may have been beneficial if “greater clot removal could be achieved and, if it is achieved, more rapidly.”
The study participants were aged between 51 and 67 years and had small to moderate intracerebral hematomas measuring less than 30 mL that were stable on computerized tomography scans.
Although the trial was neutral for the primary outcome, the researchers point out that there were significantly fewer fatalities at 6 months among the patients given alteplase, with cumulative rates of 18% versus 29% among the saline group. However, most of the additional survivors in the alteplase group had severe disability (mRS 4 or 5).
The safety profile of alteplase was favorable, with significantly lower rates of bacterial brain infections and fewer serious adverse events than with saline. The frequency of symptomatic bleeding was similar between the two groups and there were no differences in patient-reported quality of life measures.
In a related comment, Alejandro Rabinstein (Mayo Clinic, Rochester, Minnesota, USA) says that “there is a lot to learn from this trial,” adding that “it is encouraging that the pathophysiological premise of the trial was correct.”
While alteplase cannot be recommended at present, the findings indicate that “its administration is safe and aggressive clearance of the intraventricular clot, when truly achieved, might improve morbidity and mortality,” he writes.
By Lucy Piper
medwireNews is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2017