Efficacy and Safety of Intravenous Thrombolysis in Branch Atheromatous Disease

NCT07299994 | Not Yet Recruiting

• 1 other identifier: 17823177
• Study Type: observational
• Target: 462
• Locations: 3 countries
• Sites: 7

Brief Summary

Rationale and Relevance: Branch Atheromatous Disease (BAD) describes an atherosclerotic occlusion of one of the deep penetrating cerebral arteries, including the lenticulostriate artery (LSA), paramedian pontine artery (PPA), and anterior choroidal artery (ACHA). BAD is frequently associated with early neurological deterioration (END), particularly progressive motor deficits that contribute to increased disability. Despite its clinical relevance, BAD remains underrepresented in major radiomorphological classification systems such as TOAST, which has led to limited evidence and unclear treatment strategies. Previous studies suggest that the efficacy of intravenous thrombolysis (IVT) may be reduced in BAD compared to other stroke etiologies. Objectives: The primary objective of this study is to evaluate the efficacy and safety of IVT compared with single antiplatelet therapy (SAPT) and dual antiplatelet therapy (DAPT) in patients with BAD-related stroke. A secondary objective is to examine the impact of acute-phase blood pressure fluctuations on END and functional neurological outcomes. Design and Methods: This international multicenter study will be conducted retrospectively according to the STROBE guidelines. Eligible patients include those with BAD-related stroke treated at one of the participating centers between 2010 and 2025. Inclusion criteria comprise characteristic diffusion-weighted MRI patterns in predefined vascular territories (LSA, PPA, ACHA) and a symptom onset ≤24 hours before admission. Patients with typical lacunar infarcts or with other identified stroke etiologies will be excluded. Endpoints: Primary endpoints include functional outcome at three months, defined as a favorable outcome with a modified Rankin Scale score of 0-1; occurrence of END, defined as a ≥4-point worsening on the NIHSS within 24-48 hours; and symptomatic intracerebral hemorrhage. Collected data include clinical, imaging, and therapeutic variables, as well as blood pressure trajectories and pre-stroke treatments (as detailed in the study protocol). Statistical Analysis: Analyses will be performed using SPSS and R. Descriptive statistics, univariate analyses, and multivariable models (IPTW and Poisson regression) will be applied. Results will be reported as adjusted relative risks with 95% confidence intervals. Significance: This study will provide the first comprehensive evaluation of IVT versus SAPT/DAPT in BAD-related stroke, and will investigate the clinical impact of blood pressure changes in this specific stroke subtype. The findings aim to support evidence-based treatment recommendations for a currently underrecognized and poorly understood stroke etiology.

Conditions

Stroke; Thrombolysis; DAPT(Dual Antiplatelet Therapy); SAPT(Single Antiplatelet Therapy); Acute Ischemic Stroke

Keywords

Acute ischemic Stroke; Branch Atheromatous Disease; Thrombolysis; DAPT; SAPT

Outcome Measures

Primary Outcomes (3)

• Favorable outcome (mRS 0-1) at three months.

  Modified Rankin Scale (mRS) score at three months, with a favorable outcome defined as mRS 0-1 at three months.

  Three months after acute ischemic stroke treatment

• Early neurological deterioration within 24-48 hours after symptom onset

  Early neurological deterioration (END), defined as a worsening of the NIHSS score by ≥4 points within 24-48 hours after symptom onset.

  within 24-48 hours after acute ischemic stroke onset

• Occurrence of symptomatic intracerebral hemorrhage.

  Occurrence of symptomatic intracerebral hemorrhage within three months after acute ischemic stroke treatment.

  within three months after acute ischemic stroke treatment.

Secondary Outcomes (1)

• Good functional outcome (mRS 0-2)

  three months after acute ischemic stroke treatment.

Study Arms (2)

IVT group

Patients who received intravenous thrombolysis as part of acute stroke treatment, if eligible.

Antiplatelet group

Patients who received SAPT or DAPT as part of acute stroke treatment.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

All patients with a BAD-related stroke, aged over 18 years, with symptom onset no more than 24 hours before admission, who were treated in one of the stroke units of the participating institutions.

You may qualify if:

• aged over 18 years, with acute ischemic stroke and symptom onset no more than 24 hours before admission, who were treated in one of the stroke units of the participating institutions.
• DWI lesion: single isolated deep subcortical stroke AND
• The affected vessel involves the LSA, PPA, or ACHA, and the infarct lesion on DWI conforms to one of the following characteristics (A, B, OR C):
• A. LSA: "Comma-like" infarct lesions with "fan-shaped" extension from bottom to top in the coronary position OR ≥ 3 layers (layer thickness 5 mm) on axial DWI.
• B. PPA: Infarct lesion extending from the deep pons to the ventral pons on axial DWI.
• C. ACHA: Infarct within the anterior choroidal artery territory.

You may not qualify if:

• Typical recent small subcortical infarction (RSSI) (oval, \<20mm in all axes)
• ≥ 50% stenosis on the parent artery (i.e., BA, MCA, or ICA)
• Stroke due to other clearly identified causes or possible cardioembolic etiology.

Sponsors & Collaborators

• Sigmund Freud PrivatUniversitat: lead

Study Sites (7)

Department of Neurology, St. John's Hospital, Vienna, Austria

Vienna, 1020, Austria

Location

Department of Neurology, Medical University of Vienna

Vienna, 1090, Austria

Location

Department of Neurology, Berlin Institute of Health, Charité-Universitätsmedizin Berlin

Berlin, 12200, Germany

Location

Department of Neurology, Heidelberg University Hospital

Heidelberg, 69120, Germany

Location

Department of Neurology & Stroke, University of Tübingen

Tübingen, 72076, Germany

Location

Department of Neurology, Universityhospital of Bern

Bern, 3010, Switzerland

Location

Stroke Center, Neurology Service, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne

Lausanne, 1005, Switzerland

Location

Related Publications (16)

• Naimi AI, Whitcomb BW. Estimating Risk Ratios and Risk Differences Using Regression. Am J Epidemiol. 2020 Jun 1;189(6):508-510. doi: 10.1093/aje/kwaa044. No abstract available.

  PMID: 32219364 BACKGROUND

• Barow E, Boutitie F, Cheng B, Cho TH, Ebinger M, Endres M, Fiebach JB, Fiehler J, Ford I, Galinovic I, Nickel A, Puig J, Roy P, Wouters A, Magnus T, Thijs V, Lemmens R, Muir KW, Nighoghossian N, Pedraza S, Simonsen CZ, Gerloff C, Thomalla G; WAKE-UP Investigators. Functional Outcome of Intravenous Thrombolysis in Patients With Lacunar Infarcts in the WAKE-UP Trial. JAMA Neurol. 2019 Jun 1;76(6):641-649. doi: 10.1001/jamaneurol.2019.0351.

  PMID: 30907934 BACKGROUND

• Xu J, Xu X, Wang H, He L, Liu Q, Du Y, Wang J. Dual Antiplatelet Therapy Plus Argatroban Prevents Early Neurological Deterioration in Branch Atherosclerosis Disease. Stroke. 2022 Jan;53(1):e19-e20. doi: 10.1161/STROKEAHA.121.036356. Epub 2021 Nov 17.

  PMID: 34784740 BACKGROUND

• Liu B, Zhang H, Wang R, Qu H, Sun Y, Zhang W, Zhang S. Early administration of tirofiban after urokinase-mediated intravenous thrombolysis reduces early neurological deterioration in patients with branch atheromatous disease. J Int Med Res. 2020 May;48(5):300060520926298. doi: 10.1177/0300060520926298.

  PMID: 32459110 BACKGROUND

• Wu X, Liu Y, Nie C, Kang Z, Wang Q, Sun D, Li H, Liu Y, Mei B. Efficacy and Safety of Intravenous Thrombolysis on Acute Branch Atheromatous Disease: A Retrospective Case-Control Study. Front Neurol. 2020 Jul 7;11:581. doi: 10.3389/fneur.2020.00581. eCollection 2020.

  PMID: 32733357 BACKGROUND

• Kobayashi Y, Kondo Y, Yamamoto K, Hirayama S, Kuasano Y, Tazawa KI, Shimizu Y, Sato A, Sekijima Y. Tissue plasminogen activator for acute branch atheromatous disease exhibits transient improvement and worsening. J Neurol Sci. 2024 Oct 15;465:123201. doi: 10.1016/j.jns.2024.123201. Epub 2024 Aug 30.

  PMID: 39217764 BACKGROUND

• Yamamoto Y, Ohara T, Hamanaka M, Hosomi A, Tamura A, Akiguchi I. Characteristics of intracranial branch atheromatous disease and its association with progressive motor deficits. J Neurol Sci. 2011 May 15;304(1-2):78-82. doi: 10.1016/j.jns.2011.02.006. Epub 2011 Mar 13.

  PMID: 21402390 BACKGROUND

• Duan Z, Fu C, Chen B, Xu G, Tao L, Tang T, Hou H, Fu X, Yang M, Liu Z, Zhang X. Lesion patterns of single small subcortical infarct and its association with early neurological deterioration. Neurol Sci. 2015 Oct;36(10):1851-7. doi: 10.1007/s10072-015-2267-1. Epub 2015 Jun 2.

  PMID: 26032577 BACKGROUND

• Park MG, Oh EH, Kim BK, Park KP. Intravenous tissue plasminogen activator in acute branch atheromatous disease: Does it prevent early neurological deterioration? J Clin Neurosci. 2016 Nov;33:194-197. doi: 10.1016/j.jocn.2016.04.011. Epub 2016 Jul 21.

  PMID: 27452127 BACKGROUND

• Nakase T, Yoshioka S, Sasaki M, Suzuki A. Clinical evaluation of lacunar infarction and branch atheromatous disease. J Stroke Cerebrovasc Dis. 2013 May;22(4):406-12. doi: 10.1016/j.jstrokecerebrovasdis.2011.10.005. Epub 2011 Nov 30.

  PMID: 22133744 BACKGROUND

• Uchiyama S, Toyoda K, Kitagawa K, Okada Y, Ameriso S, Mundl H, Berkowitz S, Yamada T, Liu YY, Hart RG; NAVIGATE ESUS Investigators. Branch atheromatous disease diagnosed as embolic stroke of undetermined source: A sub-analysis of NAVIGATE ESUS. Int J Stroke. 2019 Dec;14(9):915-922. doi: 10.1177/1747493019852177. Epub 2019 May 27.

  PMID: 31132967 BACKGROUND

• Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon DL, Marsh EE 3rd. Classification of subtype of acute ischemic stroke. Definitions for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in Acute Stroke Treatment. Stroke. 1993 Jan;24(1):35-41. doi: 10.1161/01.str.24.1.35.

  PMID: 7678184 BACKGROUND

• Zhou L, Yao M, Peng B, Zhu Y, Ni J, Cui L. Atherosclerosis Might Be Responsible for Branch Artery Disease: Evidence From White Matter Hyperintensity Burden in Acute Isolated Pontine Infarction. Front Neurol. 2018 Oct 9;9:840. doi: 10.3389/fneur.2018.00840. eCollection 2018.

  PMID: 30356780 BACKGROUND

• Kwan MW, Mak W, Cheung RT, Ho SL. Ischemic stroke related to intracranial branch atheromatous disease and comparison with large and small artery diseases. J Neurol Sci. 2011 Apr 15;303(1-2):80-4. doi: 10.1016/j.jns.2011.01.008. Epub 2011 Feb 1.

  PMID: 21277587 BACKGROUND

• Petrone L, Nannoni S, Del Bene A, Palumbo V, Inzitari D. Branch Atheromatous Disease: A Clinically Meaningful, Yet Unproven Concept. Cerebrovasc Dis. 2016;41(1-2):87-95. doi: 10.1159/000442577. Epub 2015 Dec 16.

  PMID: 26671513 BACKGROUND

• Caplan LR. Intracranial branch atheromatous disease: a neglected, understudied, and underused concept. Neurology. 1989 Sep;39(9):1246-50. doi: 10.1212/wnl.39.9.1246. No abstract available.

  PMID: 2671793 BACKGROUND

MeSH Terms

Conditions

Stroke; Ischemic Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Julian Frederic Hotz, DDr.

  1. Department of Neurology, St. John's Hospital, Vienna, Austria, 2. Department of Neurology, University Hospital, Bern, Switzerland, 3. Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna

  PRINCIPAL INVESTIGATOR

• Marek Sykora, Prof. Dr.

  1. Sigmund Freud University Vienna, Austria, 2. Department of Neurology, St. John's Hospital, Vienna, Austria

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julian Frederic Hotz, DDr.

CONTACT

+43 1 211210; julian.hotz@meduniwien.ac.at

Marek Sykora, Prof. Dr.

CONTACT

+43 1 211210; marek.sykora@bbwien.at

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2025
• First Posted: December 23, 2025
• Study Start: January 1, 2026
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Access Criteria: Data that support the findings of this study will available from the corresponding author after academic boards review and upon reasonable request

Locations

DE (3); AU (2); CH (2)