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Clinical Trial
. 2015 Mar;76(3):291-300; discussion 301.
doi: 10.1227/NEU.0000000000000624.

Bleeding and infection with external ventricular drainage: a systematic review in comparison with adjudicated adverse events in the ongoing Clot Lysis Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR-III IHV) trial

Mahua Dey  1 , Agnieszka Stadnik, Fady Riad, Lingjiao Zhang, Nichol McBee, Carlos Kase, J Ricardo Carhuapoma, Malathi Ram, Karen Lane, Noeleen Ostapkovich, Francois Aldrich, Charlene Aldrich, Jack Jallo, Ken Butcher, Ryan Snider, Daniel Hanley, Wendy Ziai, Issam A Awad; CLEAR III Trial Investigators
Affiliations
Clinical Trial

Bleeding and infection with external ventricular drainage: a systematic review in comparison with adjudicated adverse events in the ongoing Clot Lysis Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR-III IHV) trial

Mahua Dey et al. Neurosurgery. 2015 Mar.

Abstract

Background: Retrospective series report varied rates of bleeding and infection with external ventricular drainage (EVD). There have been no prospective studies of these risks with systematic surveillance, threshold definitions, or independent adjudication.

Objective: To analyze the rate of complications in the ongoing Clot Lysis: Evaluating Accelerated Resolution of Intraventricular Hemorrhage Phase III (CLEAR III) trial, providing a comparison with a systematic review of complications of EVD in the literature.

Methods: Patients were prospectively enrolled in the CLEAR III trial after placement of an EVD for obstructive intraventricular hemorrhage and randomized to receive recombinant tissue-type plasminogen activator or placebo. We counted any detected new hemorrhage (catheter tract hemorrhage or any other distant hemorrhage) on computed tomography scan within 30 days from the randomization. Meta-analysis of published series of EVD placement was compiled with STATA software.

Results: Growing or unstable hemorrhage was reported as a cause of exclusion from the trial in 74 of 5707 cases (1.3%) screened for CLEAR III. The first 250 patients enrolled have completed adjudication of adverse events. Forty-two subjects (16.8%) experienced ≥1 new bleeds or expansions, and 6 of 250 subjects (2.4%) suffered symptomatic hemorrhages. Eleven cases (4.4%) had culture-proven bacterial meningitis or ventriculitis.

Conclusion: Risks of bleeding and infection in the ongoing CLEAR III trial are comparable to those previously reported in EVD case series. In the present study, rates of new bleeds and bacterial meningitis/ventriculitis are very low despite multiple daily injections, blood in the ventricles, the use of thrombolysis in half the cases, and generalization to >60 trial sites.

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Conflict of interest statement

The authors have no personal, financial, or institutional interest in any of the drugs, materials, or devices described in this article.

Figures

Figure 1
Figure 1
Funnel plots of A) hemorrhage rate, B) symptomatic hemorrhage rate and C) infection rate against their respective standard errors.
Figure 1
Figure 1
Funnel plots of A) hemorrhage rate, B) symptomatic hemorrhage rate and C) infection rate against their respective standard errors.
Figure 1
Figure 1
Funnel plots of A) hemorrhage rate, B) symptomatic hemorrhage rate and C) infection rate against their respective standard errors.
Figure 2
Figure 2
Forest plot of random-effects meta-analysis of the incidence rate of hemorrhages. ES, hemorrhage rate; CI, confidence interval.
Figure 3
Figure 3
Forest plot of random-effects meta-analysis of the incidence rate of symptomatic hemorrhages. ES, symptomatic hemorrhage rate; CI, confidence interval.
Figure 4
Figure 4
Forest plot of random-effects meta-analysis of the infection rates. ES, infection rate; CI, confidence interval.
See this image and copyright information in PMC

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