Evidence map›Paper›PMID 35521958›Full record

SynthesisStroke2022

Association of Intraventricular Fibrinolysis With Clinical Outcomes in Intracerebral Hemorrhage: An Individual Participant Data Meta-Analysis.

Joji B Kuramatsu, Stefan T Gerner, Wendy Ziai, Jürgen Bardutzky, Jochen A Sembill, Maximilian I Sprügel, Anne Mrochen, Kathrin Kölbl, Malathi Ram, Radhika Avadhani and 43 more

Registry-linked trialOpen access · bronzeAbstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Stroke, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06510842 (Lumbar Drainage of Intraventricular Hemorrhage The DRAIN IVH Randomized Controlled Trial), which is not on this map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
3.2field-weighted citation impact, top 7% of its field
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.

NCT06510842 narecruitingnot on this mapstarted 2025, after this paper: background citation

Lumbar Drainage of Intraventricular Hemorrhage The DRAIN IVH Randomized Controlled Trial

TypeinterventionalSponsorUniversity Hospital HeidelbergRan2025 to 2029Enrolled354ConditionsIntraventricular Hemorrhage, Lumbar Drainage, External Ventricular DrainageArmsExternal drainage of intraventricular hemorrhage
3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Article
  3. [In-hospital management of intracerebral hemorrhage].Medizinische Klinik, Intensivmedizin und Notfallmedizin · 2025
    Review
  4. Review
  5. Article
  6. Review
  7. Perioperative stroke.Nature reviews. Disease primers · 2024
    Review
  8. Article
  9. Article
  10. Article
  11. Intracerebral haemorrhage.Nature reviews. Disease primers · 2023
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

53 authors at 20 institutions in 5 countries.

Joji B Kuramatsu *Department of Neurology (J.B.K., S.T.G., J.A.S., M.I.S., A.M., K.K., D.S., S.S., H.B.H.), University of Erlangen-Nuremberg, Germany.ORCID 0000-0002-7630-7880
Stefan T Gerner *Department of Neurology (J.B.K., S.T.G., J.A.S., M.I.S., A.M., K.K., D.S., S.S., H.B.H.), University of Erlangen-Nuremberg, Germany.ORCID 0000-0001-6020-8290
Wendy Ziai *Division of Brain Injury Outcomes, Johns Hopkins University, Baltimore, MD (W.Z., M.R., R.A., D.F.H.).ORCID 0000-0003-4548-7353
Jürgen BardutzkyDepartment of Neurology, University of Freiburg, Germany (J.B.).
Jochen A SembillDepartment of Neurology (J.B.K., S.T.G., J.A.S., M.I.S., A.M., K.K., D.S., S.S., H.B.H.), University of Erlangen-Nuremberg, Germany.ORCID 0000-0003-0014-3389
Maximilian I SprügelDepartment of Neurology (J.B.K., S.T.G., J.A.S., M.I.S., A.M., K.K., D.S., S.S., H.B.H.), University of Erlangen-Nuremberg, Germany.ORCID 0000-0002-1679-9553
Anne MrochenDepartment of Neurology (J.B.K., S.T.G., J.A.S., M.I.S., A.M., K.K., D.S., S.S., H.B.H.), University of Erlangen-Nuremberg, Germany.ORCID 0000-0003-0826-4089
Kathrin KölblDepartment of Neurology (J.B.K., S.T.G., J.A.S., M.I.S., A.M., K.K., D.S., S.S., H.B.H.), University of Erlangen-Nuremberg, Germany.
Malathi RamDivision of Brain Injury Outcomes, Johns Hopkins University, Baltimore, MD (W.Z., M.R., R.A., D.F.H.).ORCID 0000-0002-6505-3037
Radhika AvadhaniDivision of Brain Injury Outcomes, Johns Hopkins University, Baltimore, MD (W.Z., M.R., R.A., D.F.H.).
Guido J FalconeDepartment of Neurology (G.J.F.), Yale University School of Medicine, New Haven, CT.ORCID 0000-0002-6407-0302
Magdy H SelimBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (M.H.S., V.A.L.).ORCID 0000-0002-1936-3173
Vasileios-Arsenios LioutasBeth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (M.H.S., V.A.L.).ORCID 0000-0002-8521-0036
Matthias EndresDepartment of Neurology (M.E., S.Z.), Charité-Universitätsmedizin Berlin, Germany.ORCID 0000-0001-6520-3720
Sarah ZweynertDepartment of Neurology (M.E., S.Z.), Charité-Universitätsmedizin Berlin, Germany.ORCID 0000-0002-1665-2666
Peter VajkoczyDepartment of Neurosurgery (P.V.), Charité-Universitätsmedizin Berlin, Germany.ORCID 0000-0003-4350-392X
Peter A RinglebDepartment of Neurology, Heidelberg University Hospital, Germany (P.A.R., J.C.P.).ORCID 0000-0002-5473-8671
Jan C PurruckerDepartment of Neurology, Heidelberg University Hospital, Germany (P.A.R., J.C.P.).ORCID 0000-0003-2978-4972
Jens VolkmannDepartment of Neurology, University of Würzburg, Germany (J.V., H.N.).ORCID 0000-0002-9570-593X
Hermann NeugebauerDepartment of Neurology, University of Würzburg, Germany (J.V., H.N.).ORCID 0000-0003-3759-356X
Frank ErbguthDepartment of Neurology, Nuremberg General Hospital, Germany (F.E.).ORCID 0000-0002-9271-198X
Peter D SchellingerDepartment of Neurology and Neurogeriatry (P.D.S.), Johannes Wesling Medical Center Minden, Germany.ORCID 0000-0002-8517-0353
Ulrich J KnappeDepartment of Neurosurgery (U.J.K.), Johannes Wesling Medical Center Minden, Germany.
Gereon R FinkDepartment of Neurology, University of Cologne, Germany (G.R.F., C.D.).ORCID 0000-0002-8230-1856
Christian DohmenDepartment of Neurology, University of Cologne, Germany (G.R.F., C.D.).
Jens MinnerupDepartment of Neurology, University of Münster, Germany (J.M.).
Heinz ReichmannDepartment of Neurology, University of Dresden, Germany (H.R., H.S.).ORCID 0000-0001-9639-1429
Hauke SchneiderDepartment of Neurology, University of Dresden, Germany (H.R., H.S.).ORCID 0000-0002-9641-0922
Joachim RötherDepartment of Neurology, Asklepios Klinikum Hamburg Altona, Germany (J.R.).ORCID 0000-0002-8088-9991
Gernot ReimannDepartment of Neurology, Klinikum Dortmund, Germany (G.R., M.S.).ORCID 0000-0001-7019-6975
Michael SchwarzDepartment of Neurology, Klinikum Dortmund, Germany (G.R., M.S.).
Hansjörg BäznerDepartment of Neurology, Klinikum Stuttgart, Germany (H.B.).ORCID 0000-0001-8944-8239
Joseph ClaßenDepartment of Neurology, University of Leipzig, Germany (J.C., D.M.).ORCID 0000-0001-7182-6967
Dominik MichalskiDepartment of Neurology, University of Leipzig, Germany (J.C., D.M.).ORCID 0000-0002-0206-5380
Otto W WitteDepartment of Neurology, University of Jena, Germany (O.W.W., A.G.).ORCID 0000-0003-2101-4105
Albrecht GüntherDepartment of Neurology, University of Jena, Germany (O.W.W., A.G.).ORCID 0000-0002-2394-3947
Gerhard F HamannDepartment of Neurology and Neurological Rehabilitation, Bezirkskrankenhaus Günzburg, Germany (G.F.H.).ORCID 0000-0001-9140-653X
Hannes LückingDepartment of Neuroradiology (H.L., A.D.), University of Erlangen-Nuremberg, Germany.ORCID 0000-0002-3935-0003
Arnd DörflerDepartment of Neuroradiology (H.L., A.D.), University of Erlangen-Nuremberg, Germany.ORCID 0000-0002-3076-3231
Muhammad Fawad IshfaqDepartment of Neurology, University of Tennessee Health Science Center, Memphis (M.F.I., A.V.A., N.G., G.T.).
Jason J ChangDepartment of Critical Care Medicine, MedStar Washington Hospital Center, Washington, DC (J.J.C.).ORCID 0000-0002-0825-3008
Fernando D TestaiDepartment of Neurology and Rehabilitation, University of Illinois College of Medicine, Chicago (F.D.T.).ORCID 0000-0002-7355-4915
Daniel WooDepartment of Neurology and Rehabilitation Medicine, University of Cincinnati, OH (D.W.).ORCID 0000-0002-2466-7155
Andrei V AlexandrovDepartment of Neurology, University of Tennessee Health Science Center, Memphis (M.F.I., A.V.A., N.G., G.T.).ORCID 0000-0001-8871-1023
Dimitre StaykovDepartment of Neurology (J.B.K., S.T.G., J.A.S., M.I.S., A.M., K.K., D.S., S.S., H.B.H.), University of Erlangen-Nuremberg, Germany.
Nitin GoyalDepartment of Neurology, University of Tennessee Health Science Center, Memphis (M.F.I., A.V.A., N.G., G.T.).ORCID 0000-0002-4699-0922
Georgios TsivgoulisDepartment of Neurology, University of Tennessee Health Science Center, Memphis (M.F.I., A.V.A., N.G., G.T.).ORCID 0000-0002-0640-3797
Kevin N ShethDepartment of Neurosurgery (G.J.F., K.N.S.), Yale University School of Medicine, New Haven, CT.ORCID 0000-0003-2003-5473
Issam A AwadDepartment of Neurosurgery, University of Chicago, IL (I.A.).ORCID 0000-0003-1510-602X
Stefan Schwab *Department of Neurology (J.B.K., S.T.G., J.A.S., M.I.S., A.M., K.K., D.S., S.S., H.B.H.), University of Erlangen-Nuremberg, Germany.ORCID 0000-0002-8487-1238
Daniel F Hanley *Division of Brain Injury Outcomes, Johns Hopkins University, Baltimore, MD (W.Z., M.R., R.A., D.F.H.).ORCID 0000-0002-9536-4258
Hagen B Huttner *Department of Neurology (J.B.K., S.T.G., J.A.S., M.I.S., A.M., K.K., D.S., S.S., H.B.H.), University of Erlangen-Nuremberg, Germany.ORCID 0000-0002-0992-8871
Collaborators
Norwegian Womens Public Health Association · NOUniversity of Tennessee Health Science Center · USHeidelberg University · DEJohannes Wesling Klinikum Minden · DEJohns Hopkins University · USBeth Israel Deaconess Medical Center · USCharité - Universitätsmedizin Berlin · DEFriedrich-Alexander-Universität Erlangen-Nürnberg · DEKlinikum Dortmund · DEKlinikum Stuttgart · DETwitter (United States) · USUniversität Ulm · DEUniversity of Cologne · DEYale University · USAsklepios Klinik Altona · DEBundeswehrkrankenhaus · DEDeichmann (Germany) · DEGerman Center for Neurodegenerative Diseases · DEJena University Hospital · DELeipzig University · DE

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Johns Hopkins-Tufts Trial Innovation Center HEAL Pain ERN SupplementU24TR001609 · NCATS · JOHNS HOPKINS UNIVERSITY · PI HANLEY, DANIEL F · 2016 to 2022
$36.3M
MISTIE III_ Lead Grant_ Cluster Application for the Clinical Coordinating CenterU01NS080824 · NINDS · JOHNS HOPKINS UNIVERSITY · PI HANLEY, DANIEL F · 2013 to 2017
$23.2M
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
NCATS NIH HHS U24 TR001609NCATS NIH HHS UL1 TR001863NINDS NIH HHS U01 NS062851NINDS NIH HHS U01 NS080824
6 · The paper itself

Abstract

backgroundIn patients with intracerebral hemorrhage (ICH), the presence of intraventricular hemorrhage constitutes a promising therapeutic target. Intraventricular fibrinolysis (IVF) reduces mortality, yet impact on functional disability remains unclear. Thus, we aimed to determine the influence of IVF on functional outcomes.

methodsThis individual participant data meta-analysis pooled 1501 patients from 2 randomized trials and 7 observational studies enrolled during 2004 to 2015. We compared IVF versus standard of care (including placebo) in patients treated with external ventricular drainage due to acute hydrocephalus caused by ICH with intraventricular hemorrhage. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS; range: 0-6, lower scores indicating less disability) at 6 months, dichotomized into mRS score: 0 to 3 versus mRS: 4 to 6. Secondary outcomes included ordinal-shift analysis, all-cause mortality, and intracranial adverse events. Confounding and bias were adjusted by random effects and doubly robust models to calculate odds ratios and absolute treatment effects (ATE).

resultsComparing treatment of 596 with IVF to 905 with standard of care resulted in an ATE to achieve the primary outcome of 9.3% (95% CI, 4.4-14.1). IVF treatment showed a significant shift towards improved outcome across the entire range of mRS estimates, common odds ratio, 1.75 (95% CI, 1.39-2.17), reduced mortality, odds ratio, 0.47 (95% CI, 0.35-0.64), without increased adverse events, absolute difference, 1.0% (95% CI, -2.7 to 4.8). Exploratory analyses provided that early IVF treatment (≤48 hours) after symptom onset was associated with an ATE, 15.2% (95% CI, 8.6-21.8) to achieve the primary outcome.

conclusionsAs compared to standard of care, the administration of IVF in patients with acute hydrocephalus caused by intracerebral and intraventricular hemorrhage was significantly associated with improved functional outcome at 6 months. The treatment effect was linked to an early time window <48 hours, specifying a target population for future trials.

Indexed as

FibrinolysisHydrocephalusCerebral HemorrhageDrainageFibrinolytic AgentsHumansObservational Studies as TopicTreatment OutcomeFibrinolytic Agentsfibrinolysishydrocephalusintracerebral hemorrhagemortalitystandard of care

Identifiers

PMID35521958
PMCPMC9398945
OpenAlexW4228996409

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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.