External Ventricular Drain With Alteplase in Intraventricular Hemorrhage Improves Outcomes

CLEAR III trial findings indicate multiple catheters in external ventricular drain treatment, as well as higher doses of alteplase, result in better efficiency and recovery.

Results from the CLEAR III trial indicate that external ventricular drain (EVD) may be a viable treatment option for intraventricular hemorrhage (IVH), a subset of intracerebral hemorrhage (ICH).

Findings from the study were presented at the 2016 International Stroke Conference in Los Angeles.

Researchers sought to determine whether or not IVH evacuation would improve functional outcomes for patients. The secondary end point was to test the mediation of Modified Rankin Scale (mRS) benefits at 180 days IVH clot reduction.

Five hundred patients from 73 sites were enrolled in CLEAR III between 2009 and 2014. EVD was administered at 11 hours post ictus and clots were determined to be stable by 52 hours, with 73% of patients experiencing at least 1 intracranial pressure (ICP) >20 mm Hg. End of treatment IVH volume was independently associated with percentage of ICP events >20 mm Hg and >30 mm Hg.

Patients were included on the basis of ICH ≤30 ml and IVH with third or fourth ventricle obstruction. Approximately half of the patients (n=249) received alteplase (1 mg every 8 hours for up to 12 doses) and the other half (n=251) received saline injections.

Alteplase led to greater end of treatment clot removal compared with saline (62% vs 44%; P<.001). However, only 21.2% of patients achieved >80% clot removal, per study protocol and guidelines. mRS 0-3 directly correlated with the extent of removal when the IVH efficiency was substituted for group assignment.

Patients with larger initial IVH volume (≥20 ml) achieved significant functional benefits (mRS 0-3; odds ratio [OR]: 1.84) with alteplase compared with placebo. Likewise, greater IVH evacuation led to more frequent mRS 0-3 (OR: 1.9 with >85% removal; OR: 2.2 with >90% removal).

In patients treated with a single catheter, alteplase achieved significantly greater IVH removal with EVD ipsilateral to dominant IVH compared with contralateral EVD (P=.004). However, in patients with IVH ≥20 ml, alteplase achieved greater removal with multiple catheters or EVDs than with a single catheter (P=.005)
Higher number of alteplase doses also facilitated better IVH removal (1.82% per dose; P=.01).

Multiple catheters, catheters in the clot (ipsilateral to dominant IVH), and more aggressive dosing led to more efficient IVH clearance, and ultimately, a significantly better recovery (OR: > 1.9) when >85% of IVH was evacuated within 4 days.

Researchers emphasized that EVD with alteplase is not “a regular EVD.” Placement in dominant IVH cast or multiple EVDs increases efficiency and treatment benefit. “Further investigation of EVD use, alteplase treatment goals, and ICP control measures are imperative,” they concluded.

More ISC 2016 coverage here.


Awad IA. Abstract LB 13. Efficiency of intraventricular hemorrhage removal determines modified Rankin scale score (CLEAR III). Presented at the International Stroke Conference; February 17-19, 2016; Los Angeles, CA.

Hanley DF. Abstract LB 12. Clot Lysis: evaluating accelerated resolution of intraventricular hemorrhage (CLEAR III) results. Presented at the International Stroke Conference; February 17-19, 2016; Los Angeles, CA.