Way forwards CLEARing for IVH intervention

By Eleanor McDermid

Results of the CLEAR III trial point the way forwards for the treatment of patients with intraventricular haemorrhage (IVH).

Although the trial failed to meet its primary endpoint, the two presentations given today at the International Stroke Conference show that alteplase improves treatment outcomes for patients with haemorrhages larger than 20 mL and for all patients if a sufficiently large proportion of the clot is removed.

Included patients had intracerebral haemorrhage no larger than 30 mL, and IVH with third or fourth ventricle obstruction. The researchers used adaptive randomisation to avoid imbalances in patients with different IVH volumes; however, they had not anticipated the high proportion of patients with IVH volumes of less than 20 mL.

These patients, revealed Daniel Hanley (Johns Hopkins University, Baltimore, Maryland, USA), did not benefit from the addition of alteplase during clot removal. And because these patients comprised 44% of the study population, their presence precluded an overall positive result.

There were 500 patients in the trial, and they were randomly assigned between 12 and 72 hours after onset to receive alteplase (1 mg every 8 hours to a maximum 12 doses) or saline through an extraventricular drain (EVD).

Alteplase had no overall impact on the primary outcome of a score of 0-3 on the modified Rankin Scale (mRS) at 180 days, at a rate of 48% versus 45% for saline, despite achieving a significant reduction in 180-day mortality. However, the 274 patients with IVH volumes of 20 mL or greater were a significant 1.87-fold more likely to achieve the primary outcome if they received alteplase rather than saline.

But outcome was determined also by the efficiency of clot removal; Issam Awad (University of Chicago, Illinois, USA) showed a "strong and direct" correlation between the efficiency of clot removal and mRS 0-3. The effect was seen even in patients with small IVH volumes, although it was stronger in those with larger volumes.

Greater than 85% clot removal increased the odds of achieving mRS 0-3 a significant 1.91-fold and greater than 90% removal increased the odds 2.25-fold. But a minimum 80% clot removal was achieved in just 33% of patients given alteplase and 10% given saline.

Several surgical factors contributed to the efficiency of clot removal; more doses of alteplase, placement of single EVDs directly in the clot (ipsilateral to dominant IVH) and use of multiple EVDs for IVH volumes larger than 20 mL.

Awad said the implications for clinical practice are "inescapable", with training needed in the optimal placement of EVDs for IVH, as distinct from hydrocephalus or high intracranial pressure. But he also stressed that the effectiveness of "vigorous, goal-directed" clot removal needs to be properly tested in general practice - the aim of CLEAR IV.

Licensed from medwireNews with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.