Evidence map›Paper›PMID 27751554›Full record

Trial reportThe Lancet. Neurology2016

Safety and efficacy of minimally invasive surgery plus alteplase in intracerebral haemorrhage evacuation (MISTIE): a randomised, controlled, open-label, phase 2 trial.

Daniel F Hanley, Richard E Thompson, John Muschelli, Michael Rosenblum, Nichol McBee, Karen Lane, Amanda J Bistran-Hall, Steven W Mayo, Penelope Keyl, Dheeraj Gandhi and 25 more

3 registry-linked trialsAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Neurology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 184 papers, 14 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
184citing papers in PubMed, 14 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00224770 phase2completednot on this map

Minimally Invasive Surgery and rtPA for Intracerebral Hemorrhage Evacuation

TypeinterventionalSponsorDaniel HanleyRan2005 to 2013Enrolled141ConditionsIntracerebral HemorrhageArmsMIS+Cathflo Activase (drug), Intraoperative stereotactic CT-Guided Endoscopic Surgery
NCT03414307 nawithdrawnnot on this mapstarted 2020, after this paper: background citation

ROSA Stereotactic Robot-assisted Intracerebral Hemorrhage Clot Evacuation

TypeinterventionalSponsorZimmer BiometRan2020 to 2020Enrolled0ConditionsIntracerebral HematomaArmsIntracerebral catheter placement, Robot-assisted intracerebral catheter
NCT04172376 naunknown statusnot on this mapstarted 2021, after this paper: background citation

Stereotactic Operation Integrating With Thrombolysis in Basal Ganglion Hemorrhage Evacuation II (SOITBE II)

TypeinterventionalSponsorSecond Affiliated Hospital, Zhejiang University, School of MedicineRan2021 to 2023Enrolled400ConditionsBasal Ganglia HemorrhageArmsMinimally invasive puncture aspiration plus rt-PA, Conservative medical treatment
3 · Its place in the literature

Who cites it

184 citing papers in PubMed, 14 syntheses or guidelines pooled it.

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  4. Surgery for spontaneous supratentorial intracerebral haemorrhage.The Cochrane database of systematic reviews · 2025
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  15. Trial
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  19. [Hematoma Segmentation of Spontaneous Intracerebral Hemorrhage Based on Watershed and Region-Growing Algorithm].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2022
    Trial
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124 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

35 authors.

Daniel F HanleyDepartment of Neurology, Brain Injury Outcomes Coordinating Center, Johns Hopkins University, Baltimore, MD, USA. Electronic address: dhanley@jhmi.edu.
Richard E ThompsonDepartment of Biostatistics, School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
John MuschelliDepartment of Biostatistics, School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Michael RosenblumDepartment of Biostatistics, School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Nichol McBeeDepartment of Neurology, Brain Injury Outcomes Coordinating Center, Johns Hopkins University, Baltimore, MD, USA.
Karen LaneDepartment of Neurology, Brain Injury Outcomes Coordinating Center, Johns Hopkins University, Baltimore, MD, USA.
Amanda J Bistran-HallDepartment of Neurology, Brain Injury Outcomes Coordinating Center, Johns Hopkins University, Baltimore, MD, USA.
Steven W MayoEmissary International, Austin, TX, USA.
Penelope KeylDepartment of Neurology, Brain Injury Outcomes Coordinating Center, Johns Hopkins University, Baltimore, MD, USA.
Dheeraj GandhiDepartment of Neuroradiology, University of Maryland, Baltimore, MD, USA.
Tim C MorganDepartment of Neurology, Brain Injury Outcomes Coordinating Center, Johns Hopkins University, Baltimore, MD, USA.
Natalie UllmanDepartment of Neurology, Brain Injury Outcomes Coordinating Center, Johns Hopkins University, Baltimore, MD, USA.
W Andrew MouldDepartment of Neurology, Brain Injury Outcomes Coordinating Center, Johns Hopkins University, Baltimore, MD, USA.
J Ricardo CarhuapomaDepartment of Neurology, Brain Injury Outcomes Coordinating Center, Johns Hopkins University, Baltimore, MD, USA.
Carlos KaseDepartment of Neurology, Boston University, Boston, MA, USA.
Wendy ZiaiDepartment of Neurology, Brain Injury Outcomes Coordinating Center, Johns Hopkins University, Baltimore, MD, USA.
Carol B ThompsonDepartment of Biostatistics, School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Gayane YenokyanDepartment of Biostatistics, School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
Emily HuangDepartment of Biostatistics, School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
William C BroaddusDepartment of Neurology, Virginia Commonwealth University, Richmond, VA, USA.
R Scott GrahamDepartment of Neurosurgery, Virginia Commonwealth University, Richmond, VA, USA.
E Francois AldrichDepartment of Neurosurgery, University of Maryland, Baltimore, MD, USA.
Robert DoddDepartment of Neurosurgery, Stanford University, Palo Alto, CA, USA.
Cristanne WijmanDepartment of Neurology, Stanford University, Palo Alto, CA, USA.
Jean-Louis CaronDepartment of Neurosurgery, University of Texas, San Antonio, TX, USA.
Judy HuangDepartment of Neurosurgery, Johns Hopkins University, Baltimore, MD, USA.
Paul CamarataDepartment of Neurosurgery, University of Kansas, Kansas City, KS, USA.
A David MendelowNeurosurgery, Newcastle University, Newcastle upon Tyne, UK.
Barbara GregsonNeurosurgery, Newcastle University, Newcastle upon Tyne, UK.
Scott JanisNational Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Paul VespaDepartment of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
Neil MartinDepartment of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, USA.
Issam AwadDepartment of Neurosurgery, University of Chicago, Chicago, IL, USA.
Mario ZuccarelloDepartment of Neurosurgery, University of Cincinnati, Cincinnati, OH, USA.
MISTIE Investigators

Funding

Clot Lysis: Evaluating Accelerated Resolution of IVH Phase III (CLEAR III)U01NS062851 · NINDS · JOHNS HOPKINS UNIVERSITY · PI HANLEY, DANIEL F · 2009 to 2013
$21.6M
EPIDEMIOLOGY AND BIOSTATISTICS OF AGINGT32AG000247 · NIA · JOHNS HOPKINS UNIVERSITY · PI Karen J. Bandeen-Roche · 1996 to 2026
$13.2M
ICH Removal: Minimally Invasive Surgery + rt-PAR01NS046309 · NINDS · JOHNS HOPKINS UNIVERSITY · PI HANLEY, DANIEL F · 2005 to 2011
$9.1M
NIA NIH HHS T32 AG000247NINDS NIH HHS R01 NS046309NINDS NIH HHS U01 NS062851
6 · The paper itself

Abstract

backgroundCraniotomy, according to the results from trials, does not improve functional outcome after intracerebral haemorrhage. Whether minimally invasive catheter evacuation followed by thrombolysis for clot removal is safe and can achieve a good functional outcome is not known. We investigated the safety and efficacy of alteplase, a recombinant tissue plasminogen activator, in combination with minimally invasive surgery (MIS) in patients with intracerebral haemorrhage.

methodsMISTIE was an open-label, phase 2 trial that was done in 26 hospitals in the USA, Canada, the UK, and Germany. We used a computer-generated allocation sequence with a block size of four to centrally randomise patients aged 18-80 years with a non-traumatic (spontaneous) intracerebral haemorrhage of 20 mL or higher to standard medical care or image-guided MIS plus alteplase (0·3 mg or 1·0 mg every 8 h for up to nine doses) to remove clots using surgical aspiration followed by alteplase clot irrigation. Primary outcomes were all safety outcomes: 30 day mortality, 7 day procedure-related mortality, 72 h symptomatic bleeding, and 30 day brain infections. This trial is registered with ClinicalTrials.gov, number NCT00224770.

findingsBetween Feb 2, 2006, and April 8, 2013, 96 patients were randomly allocated and completed follow-up: 54 (56%) in the MIS plus alteplase group and 42 (44%) in the standard medical care group. The primary outcomes did not differ between the standard medical care and MIS plus alteplase groups: 30 day mortality (four [9·5%, 95% CI 2·7-22.6] vs eight [14·8%, 6·6-27·1], p=0·542), 7 day mortality (zero [0%, 0-8·4] vs one [1·9%, 0·1-9·9], p=0·562), symptomatic bleeding (one [2·4%, 0·1-12·6] vs five [9·3%, 3·1-20·3], p=0·226), and brain bacterial infections (one [2·4%, 0·1-12·6] vs zero [0%, 0-6·6], p=0·438). Asymptomatic haemorrhages were more common in the MIS plus alteplase group than in the standard medical care group (12 [22·2%; 95% CI 12·0-35·6] vs three [7·1%; 1·5-19·5]; p=0·051).

interpretationMIS plus alteplase seems to be safe in patients with intracerebral haemorrhage, but increased asymptomatic bleeding is a major cautionary finding. These results, if replicable, could lead to the addition of surgical management as a therapeutic strategy for intracerebral haemorrhage.

fundingNational Institute of Neurological Disorders and Stroke, Genentech, and Codman.

Indexed as

Outcome Assessment, Health CareAgedCerebral HemorrhageCombined Modality TherapyFemaleFibrinolytic AgentsFollow-Up StudiesHumansMaleMiddle AgedMinimally Invasive Surgical ProceduresPostoperative HemorrhageSurgery, Computer-AssistedThrombectomyTissue Plasminogen ActivatorFibrinolytic AgentsTissue Plasminogen Activator

Identifiers

PMID27751554
PMCPMC5154627

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.