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Does stereotactic thrombolysis with alteplase for intracerebral haemorrhage alter intraventricular haematoma volume? A secondary analysis of the MISTIE-III trial
  1. Philip Sun1,
  2. Shervin Badihian2,3,
  3. Radhika Avadhani2,
  4. Nathan Walborn2,
  5. Anusha Yarava2,
  6. Donya Alimoradi2,
  7. Issam Awad4,
  8. Daniel Hanley2,
  9. Santosh Murthy5,
  10. Wendy Ziai1,2
  1. 1Departments of Neurology, Anesthesiology & Critical Care Medicine, Johns Hopkins University, Baltimore, Maryland, USA
  2. 2Department of Neurology, Division of Brain Injury Outcomes, Johns Hopkins University, Baltimore, Maryland, USA
  3. 3Department of Neurology, Cleveland Clinic, Cleveland, Ohio, USA
  4. 4Department of Neurosurgery, University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA
  5. 5Department of Neurology, Cornell University Joan and Sanford I Weill Medical College, New York, New York, USA
  1. Correspondence to Professor Wendy Ziai, Neurology, Johns Hopkins Medical Institutions Campus, Baltimore, MD 21287, USA; weziai{at}


Background Stereotactic thrombolysis reduces intracerebral haemorrhage (ICH) volume in patients with spontaneous ICH. Whether intrahaematomal alteplase administration is associated with a change in intraventricular haemorrhage volume (deltaIVH) and functional outcomes is unknown.

Methods Post hoc secondary analysis of the Minimally Invasive Surgery plus Alteplase for Intracerebral Hemorrhage Evacuation Phase III (MISTIE-III) trial in patients with IVH on the stability CT scan. Exposure was minimally invasive surgery plus alteplase (MIS+alteplase). Primary outcome was deltaIVH defined as IVH volume on end-of-treatment CT minus IVH volume on stability CT scan. Secondary outcomes were favourable functional outcome (modified Rankin Scale 0–3) and mortality at 365 days. We assessed the relationship between MIS+alteplase and deltaIVH in the primary analysis using multivariable linear regression, and between deltaIVH and functional outcomes in secondary analyses using multiple logistic regression.

Results Of 499 patients in MISTIE-III, 310 (62.1%) had IVH on stability scans; mean age (SD) was 61.2±12.3 years. A total of 146 (47.1%) received the MISTIE procedure and 164 (52.9%) standard medical care (SMC) only. The MIS+alteplase group had a greater mean reduction in IVH volume compared with the SMC group (deltaIVH: −2.35 (5.30) mL vs −1.15 (2.96) mL, p=0.02). While IVH volume decreased significantly in both treatment groups, in the primary analysis, MIS+alteplase was associated with greater deltaIVH in multivariable linear regression analysis adjusted for potential confounders (β −0.80; 95% CI −1.37 to −0.22, p=0.007). Secondary analysis demonstrated no associations between IVH reduction and functional outcomes (adjusted OR (aOR) for poor outcome 1.02; 95% CI 0.96 to 1.08, p=0.61; aOR for mortality 0.99; 95% CI 0.92 to 1.06, p=0.77).

Conclusions Alteplase delivered into the ICH in MISTIE-III subjects with IVH was associated with a small reduction in IVH volume. This reduction did not translate into a significant benefit in mortality or functional outcomes at 365 days.

Trial registration number NCT01827046.


Data availability statement

Data are available upon reasonable request. Interested researchers may formally request access to the dataset by submitting a proposal.

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Data availability statement

Data are available upon reasonable request. Interested researchers may formally request access to the dataset by submitting a proposal.

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  • X @shervinbd, @san_murthy

  • Contributors PS: acquisition of data, analysis and interpretation of data, preparation of figures 2–4 and tables, drafting and revising the article. SB: preparation of figures and revising the article. RA: acquisition of data, analysis and interpretation of data, revising the article. NW: preparation of figure 1. AY: analysis and data interpretation. IA, DH, SM: drafting and revising the manuscript. WZ: conception and design, analysis and data interpretation, drafting and revising the manuscript;

    accepts full responsibility for the work and/or the conduct of the study, had access to the data, and controlled the decision to publish

    . All authors contributed to the manuscript and approved the submitted version.

  • Funding This research was funded by NIH/NINDS (Grant No 11054953) (principal investigator: DH) as part of the MISTIE-III: Minimally Invasive Surgery and rt-PA in ICH Evacuation Phase III.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

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