Efficacy and Safety of Intravenous Thrombolysis in Branch Atheromatous Disease

July 14, 2026 updated by: Sigmund Freud PrivatUniversitat

Efficacy and Safety of Intravenous Thrombolysis in Branch Atheromatous Disease - a Retrospective Data Analysis

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.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Intracranial branch atheromatous disease (BAD )describes an occlusion of deep penetrating intracranial arteries, leading to subcortical infarction. These perforators include the lenticulostriate arteries (LSA), paramedian pontine arteries (PPA), anterior choroidal artery (ACHA), thalamoperforating arteries, and Heubner's artery. This study specifically focuses on BAD affecting the LSA, PPA, and ACHA territories.

Unlike classical lacunar infarction, which is typically attributed to lipohyalinotic degeneration or fibrinoid necrosis of small distal perforators (<200 µm), BAD involves more proximal and larger perforating arteries (approximately 700-800 µm in diameter). The underlying pathophysiology is thought to be predominantly atherosclerotic plaque involvement at or near the origin of the perforating artery from a parent vessel, resulting in progressive luminal narrowing, branch occlusion, or flow impairment. This distinguishes BAD from traditional small vessel disease and places it within a spectrum of intracranial atherosclerotic disease.

Despite its distinct vascular mechanism, BAD is not formally classified as a separate etiological subtype in major stroke classification systems such as TOAST or NINDS criteria. As a result, cases are often categorized under "small vessel occlusion" or "stroke of undetermined etiology," contributing to under-recognition and limited systematic evidence regarding optimal management strategies.

Clinically, BAD may initially present similarly to lacunar stroke syndromes, particularly pure motor or sensorimotor deficits. However, a main feature is early neurological deterioration (END), typically occurring within the first 24-48 hours after onset. END is characterized by stepwise or progressive worsening of neurological deficits, most commonly motor impairment, which is thought to reflect ongoing ischemia due to dynamic thrombo-atherosclerotic processes, hemodynamic instability, or progressive perforator occlusion. This clinical course is associated with worse functional outcomes and higher rates of long-term disability compared with stable lacunar infarcts.

From a therapeutic perspective, optimal acute management of BAD remains uncertain. Intravenous thrombolysis (IVT), while standard for acute ischemic stroke within the therapeutic window, appears to yield less consistent benefit in BAD compared to other stroke subtypes.

Given these uncertainties, this study aims to evaluate real-world treatment effectiveness of IVT compared with antiplatelet-based strategies in patients with imaging-confirmed BAD. In addition, the study investigates the potential role of early hemodynamic variability, particularly blood pressure fluctuations, as a modifiable factor influencing END and functional outcome.

This is an international, multicenter, retrospective observational cohort study conducted according to STROBE guidelines. Participating stroke centers contribute consecutively treated patients meeting predefined radiological and clinical criteria over a 15-year period. All included patients underwent standardized neuroimaging with MRI, allowing for consistent identification of infarct topography and exclusion of alternative stroke mechanisms.

Clinical data, imaging findings, acute treatment strategies, blood pressure profiles, and outcome measures are extracted from institutional stroke databases and anonymized prior to central analysis. Comparative effectiveness analyses will be performed to assess differences between treatment groups, with adjustment for baseline imbalances using appropriate statistical methods, including propensity score-based approaches.

Overall, this study seeks to address a gap in stroke literature by providing multicenter evidence on the comparative effectiveness of intravenous thrombolysis versus antiplatelet strategies in BAD, while simultaneously clarifying the prognostic significance of early hemodynamic changes in this under-recognized stroke subtype.

Study Type

Observational

Enrollment (Estimated)

462

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Austria
      • Vienna, Austria, 1020
        • Recruiting
        • Department of Neurology, St. John's Hospital, Vienna, Austria
        • Contact:
        • Contact:
      • Vienna, Austria, 1090
    • State of Vienna
  • Germany
      • Berlin, Germany, 12200
        • Not yet recruiting
        • Department of Neurology, Berlin Institute of Health, Charité-Universitätsmedizin Berlin
        • Contact:
      • Heidelberg, Germany, 69120
      • Tübingen, Germany, 72076
        • Recruiting
        • Department of Neurology & Stroke, University of Tübingen
        • Contact:
  • Switzerland
      • Bern, Switzerland, 3010
        • Not yet recruiting
        • Department of Neurology, Universityhospital of Bern
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

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.

Description

Inclusion Criteria:

  • 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.

  • All enrolled patients must have undergone a cerebral MRI for inclusion:

    1. DWI lesion: single isolated deep subcortical stroke AND
    2. 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Favorable outcome (mRS 0-1) at three months.
Time Frame: Three months after acute ischemic stroke treatment
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
Time Frame: within 24-48 hours after acute ischemic stroke 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.
Time Frame: within three months after acute ischemic stroke treatment.
Occurrence of symptomatic intracerebral hemorrhage within three months after acute ischemic stroke treatment.
within three months after acute ischemic stroke treatment.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Good functional outcome (mRS 0-2)
Time Frame: three months after acute ischemic stroke treatment.
Modified Rankin Scale (mRS) score at three months, with a good outcome defined as mRS 0-2 at three months.
three months after acute ischemic stroke treatment.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sigmund Freud PrivatUniversitat

Investigators

  • Principal Investigator: 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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2026

Primary Completion (Estimated)

December 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

December 10, 2025

First Submitted That Met QC Criteria

December 10, 2025

First Posted (Actual)

December 23, 2025

Study Record Updates

Last Update Posted (Actual)

July 16, 2026

Last Update Submitted That Met QC Criteria

July 14, 2026

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17823177

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participant data that underlie the results after deidentification

IPD Sharing Access Criteria

Data that support the findings of this study will available from the corresponding author after academic boards review and upon reasonable request

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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