Evidence map›Paper›PMID 31320933›Full record

ArticleTherapeutic advances in neurological disorders2019

Endovascular equipoise shift in a phase III randomized clinical trial of sonothrombolysis for acute ischemic stroke.

Andrei V Alexandrov, Georgios Tsivgoulis, Martin Köhrmann, Aristeidis H Katsanos, Lauri Soinne, Andrew D Barreto, Travis Rothlisberger, Vijay K Sharma, Robert Mikulik, Keith W Muir and 12 more

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PubMed Full text at PMC Publisher
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Article in Therapeutic advances in neurological disorders, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
  2. Role of Ultrasound-Based Therapies in Cardiovascular Diseases.Structural heart : the journal of the Heart Team · 2025
    Review
  3. Review
  4. Article
  5. Article
  6. Review
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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

22 authors.

Andrei V AlexandrovDepartment of Neurology, University of Tennessee Health Science Center, 855 Monroe Avenue, Suite 415, Memphis, TN 38163, USA.ORCID https://orcid.org/0000-0001-8871-1023
Georgios TsivgoulisDepartment of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA.
Martin KöhrmannDepartment of Neurology, Universitaetsklinikum Erlangen, Erlangen, Germany.
Aristeidis H KatsanosSecond Department of Neurology, 'Attikon' University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Lauri SoinneDepartment of Neurology, Helsinki University Hospital and Clinical Neurosciences, Neurology, University of Helsinki Helsinki, Finland.
Andrew D BarretoDepartment of Neurology, University of Texas Health Science Center at Houston, Houston, TX, USA.
Travis RothlisbergerCerevast Therapeutics, Inc., Redmond, WA, USA.
Vijay K SharmaYong Loo Lin School of Medicine, National University of Singapore and Division of Neurology, Department of Medicine, National University Hospital, Singapore, Singapore.
Robert MikulikInternational Clinical Research Centre and Department of Neurology, St. Anne's University Hospital in Brno and Medical Faculty, Masaryk University, Brno, Czech Republic.
Keith W MuirInstitute of Neuroscience and Psychology, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, UK.
Christopher R LeviDepartment of Neurology, John Hunter Hospital, University of Newcastle, Newcastle, Australia.
Carlos A MolinaStroke Unit, Department of Neurology, Vall d'Hebron University Hospital, Vall d'Hebron Research Institute, Autonomous University of Barcelona, Barcelona, Spain.
Maher SaqqurDepartment of Medicine (Neurology), University of Alberta, Edmonton, Alberta, Canada.
Dimitris MavridisDepartment of Primary Education, School of Education, University of Ioannina, Ioannina, Greece.
Theodora PsaltopoulouDepartment of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Milan R VoskoDepartment of Neurology 2, Med Campus III, Kepler University Hospital, Linz, Austria.
Jochen B FiebachCenter for Stroke Research Berlin, Charité-University Medicine Berlin, Berlin, Germany.
Pitchaiah MandavaStroke Outcomes Laboratory, Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
Thomas A KentStroke Outcomes Laboratory, Department of Neurology, Baylor College of Medicine, Houston, TX, USA.
Anne W AlexandrovDepartment of Neurology, University of Tennessee Health Science Center, Memphis, TN, USA.
Peter D SchellingerDepartments of Neurology and Neurogeriatry, John Wesling Medical Center Minden, Ruhr University Bochum, Minden, Germany.
CLOTBUST-ER Trial Investigators

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundResults of our recently published phase III randomized clinical trial of ultrasound-enhanced thrombolysis (sonothrombolysis) using an operator-independent, high frequency ultrasound device revealed heterogeneity of patient recruitment among centers.

methodsWe performed a post hoc analysis after excluding subjects that were recruited at centers reporting a decline in the balance of randomization between sonothrombolysis and concurrent endovascular trials.

resultsFrom a total of 676 participants randomized in the CLOTBUST-ER trial we identified 52 patients from 7 centers with perceived equipoise shift in favor of endovascular treatment. Post hoc sensitivity analysis in the intention-to-treat population adjusted for age, National Institutes of Health Scale score at baseline, time from stroke onset to tPA bolus and baseline serum glucose showed a significant (p < 0.01) interaction of perceived endovascular equipoise shift on the association between sonothrombolysis and 3 month functional outcome [adjusted common odds ratio (cOR) in centers with perceived endovascular equipoise shift: 0.22, 95% CI 0.06-0.75; p = 0.02; adjusted cOR for centers without endovascular equipoise shift: 1.20, 95% CI 0.89-1.62; p = 0.24)]. After excluding centers with perceived endovascular equipoise shift, patients randomized to sonothrombolysis had higher odds of 3 month functional independence (mRS scores 0-2) compared with patients treated with tPA only (adjusted OR: 1.53; 95% CI 1.01-2.31; p = 0.04).

conclusionOur experience in CLOTBUST-ER indicates that increasing implementation of endovascular therapies across major academic stroke centers raises significant challenges for clinical trials aiming to test noninterventional or adjuvant reperfusion strategies.

Indexed as

endovascularequipoise shiftintracranial hemorrhagemechanical thrombectomyoutcomerecanalizationsonothrombolysisstrokeultrasound-enhanced thrombolysis

Identifiers

PMID31320933
PMCPMC6628520

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Registered trials

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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.