The International PERForator ANeurysm Registry (PERFAN) (PERFAN)

December 18, 2023 updated by: Insel Gruppe AG, University Hospital Bern

The International PERForator ANeurysm Registry (PERFAN) - Natural History, Treatment, and Outcome of Intracranial Perforator Aneurysms

The goal of this international, multicenter, mixed retrospective-prospective, exploratory, observational study is to establish an international registry to fill the knowledge gap created by the rarity of lenticulostriate and basilar perforator aneurysms and the resulting lack of knowledge about their natural history, diagnostic evaluation, management, and clinical outcomes. Specifically, comparative analyses of outcomes in patients with intracranial perforator aneurysms treated conservatively, endovascularly, and surgically will be performed. The study will also evaluate the size and location of lenticulostriate and basilar intracranial perforator aneurysms, collect information on the specific type of endovascular treatment used, compare patients with predominantly perimesencephalic subarachnoid hemorrhage (SAH) who have a perforator aneurysm to those without, and evaluate spontaneous occlusion in conservatively treated aneurysms. Core lab analysis of these aneurysms on various imaging modalities will be performed at the Inselspital and changes in aneurysm characteristics over time will be documented. In addition, the relationship between baseline characteristics and aneurysm characteristics on the incidence of hemorrhage will be examined. The study will involve approximately 20-30 centers worldwide with an estimated total sample size of 200-300 patients by 2025.

Study Overview

Status

Recruiting

Conditions

Detailed Description

  1. Background and current state of research

    Lenticulostriate and basilar perforator aneurysms are extremely rare subtypes of intracranial aneurysms. Recent years have seen an increase in their diagnosis due to advancements in imaging technology. However, their low incidence has left a significant gap in the understanding of their natural history, diagnostic evaluation, management, and clinical outcomes. To date, the available literature consists mainly of case reports or small case series, with only a limited number of systematic reviews, such as those on lenticulostriate aneurysms (112 cases) and basilar perforator aneurysms (54 patients).

    The most common presentation of perforator aneurysms is rupture, although unruptured aneurysms may be diagnosed as an incidental finding or as the cause of compressive symptoms. Initial angiography fails to identify approximately 30%-60% of perforator aneurysms. Various treatment approaches have been reported, including surgery and various endovascular techniques such as coiling, embolization with liquid embolic agents, flow-diverters, and even electrothrombosis with a microguidewire. However, all invasive strategies have inherent periprocedural risks that must be carefully weighed against the reported overall high rate of favorable outcomes in conservatively managed patients.

    Despite the growing interest and knowledge in this field, an international multicenter registry that includes baseline patient characteristics, imaging, follow-up protocols, treatment strategies, and outcomes for both ruptured and unruptured intracranial perforator aneurysms is still lacking.

  2. Research questions, hypotheses and aims

    The research questions of this exploratory study are:

    • To conduct a comparative analysis of clinical characteristics and outcomes among patients with intracranial lenticulostriate and basilar perforator aneurysms treated conservatively, endovascularly, and surgically.
    • To assess the size and exact location of lenticulostriate and basilar intracranial perforator aneurysms.
    • To gather information regarding the specific type of endovascular treatment employed.
    • To compare patients with predominantly perimesencephalic SAH harboring a perforator aneurysm and those without an aneurysm.
    • To investigate the occurrence of spontaneous occlusion in aneurysms treated conservatively.
    • To perform a core lab analysis of lenticulostriate and basilar intracranial perforator aneurysms using different imaging modalities, including computed tomography (CT), magnetic resonance imaging (MRI), 2D digital subtraction angiography (DSA), and 3D DSA.
    • To review and document observed changes of lenticulostriate and basilar perforator aneurysms (e.g. size) on follow-up imaging.
    • To examine the association between aneurysm size and the incidence of bleeding.

  3. Methods

    3.1 Study population

    This is an international, multicenter, mixed-retrospective-prospective exploratory observational study.

    So far, in Switzerland, the Inselspital, the University Hospital Basel, the University Hospital Lausanne, the Regional Hospital of Lugano and the Cantonal Hospital St. Gallen are participating in this study and have received ethical approval. In addition, since the start of the study in early November 2023, already 15 international centers have expressed their interest in participating. More centers worldwide will be contacted via a distribution list [European Society of Minimally Invasive Neurological Therapy (ESMINT); Society of Neurointerventional Surgery (SNIS)] and invited to participate. The investigators estimate that approximately 20-30 centers worldwide will participate with an estimated total sample size of 200-300 patients by 2025. The analysis will be based on a survey (see below for included data) specifically designed for this study and completed by local neuroradiologists, neurologists or neurosurgeons involved in the management of intracranial perforator aneurysms. The primary treating physician will review the clinical records of patients with intracranial perforator aneurysms treated conservatively, endovascularly, or surgically. Study lead and coordination as well as radiological and statistical analysis will be performed by the team at the Inselspital, Bern, Switzerland.

    3.2 Baseline characteristics, imaging variables, treatment variables, and outcome variables

    Data include:

    • Age, sex, relevant comorbidities such as e.g. hypertension, arteriovenous malformation (AVM), Moya-Moya, initial clinical presentation (incidental vs. hemorrhagic). In case of hemorrhagic presentation the type of bleeding [SAH, perimesencephalic subarachnoid hemorrhage (pmSAH), intraventricular hemorrhage (IVH), or intracerebral hemorrhage (ICH)] will be documented.
    • Type of initial diagnostic modality (CT, MRI, DSA).
    • Perforator aneurysm identified on initial diagnostic modality.
    • Type of treatment (surgical vs. endovascular). In case of endovascular treatment specific type [coiling, n-butyl cyanoacrylate (NBCA), ethylene vinyl alcohol (EVOH), flow-diverter, Electro-coagulation, other].
    • Pre- and post-treatment modified Rankin Scale (mRS).

    Clinical endpoints include:

    • mRS at 3 months after initial diagnosis of an intracranial perforator aneurysm
    • mRS at last follow-up (including time-point of last follow-up after diagnosis)
    • Rupture/re-rupture of the index aneurysm as a time-event outcome

    Safety endpoints include:

    • Death during the acute hospital stay
    • Death up to 90 days (related to the index aneurysm)
    • Ischemic stroke (imaging based)
    • Periprocedural and postprocedural complications in patients submitted to endovascular or surgical treatment.

    Efficacy Endpoint

    • For patients receiving treatment, assessment of aneurysm occlusion after treatment and available follow-ups.

    3.3 Data transfer and storage (Medical-Blocks® and REDCap)

    Imaging data from all external participating centers will be securely transferred via and stored on Medical-Blocks® (https://mb-neuro.medical-blocks.ch). This cloud-based platform for storage, anonymization and exchange of medical images in the neuro field (MB-Neuro) is provided by the Inselspital Bern. The platform provides the necessary interfaces to communicate with other secure and advanced IT environments via various Application Programming Interfaces (APIs). Secure Sockets Layers (SSL) with 256-bit encryption is used, which complies with the regulations of KlinV. (Verordnung über klinische Versuche) Art. 18 and HFV (Humanforschungsverordnung) Art. 5 of the Swiss Ordinance on the Storage of Health-Related Personal Data and Biological Materials. The clinical datasets will be provided in an anonymized fashion (matching the anonymized imaging data) by the physician primarily involved in patient management from the participating centers and entered and stored in REDCap.

  4. Sample size and statistical analyses

This is an exploratory study. The investigators estimate that approximately 20-30 centers worldwide will participate with an estimated total sample size of 200-300 patients.

Categorical variables will be presented as numbers and percentages, and continuous variables as medians, interquartile range (IQR). Fisher's exact will be used for categorical and Mann-Whitney U test or Kruskal-Wallis test for continuous variables. Logistic regression results will be displayed as odds ratios (OR) for simple regression or adjusted OR (aOR) for multinomial regression analyses, with their corresponding 95% confidence intervals (CIs). As this is an exploratory study, no conclusions about significance can be drawn. Therefore, a p-value < 0.05 will be interpreted as a trend. All analyses will be performed using established statistic software, including R 4.01 or newer, Python 3.83 or newer, Stata 16 and/or Statistical Package for the Social Sciences (SPSS) 27.00 or newer.

Study Type

Observational

Enrollment (Estimated)

300

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

  • Name: Tomas Dobrocky, PD, MD
  • Phone Number: +41 31 63 2 68 81
  • Email: perfan@insel.ch

Study Contact Backup

  • Name: Bettina L. Serrallach, MD
  • Phone Number: +41 31 63 2 78 69
  • Email: perfan@insel.ch

Study Locations

  • Switzerland
      • Bern, Switzerland, 3010
        • Recruiting
        • Institute of Diagnostic and Interventional Neuroradiology, Inselspital Bern
        • Contact:
        • 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

Patients.

Description

Inclusion Criteria:

  • Patients from the Inselspital and from participating centers worldwide, who have been diagnosed or will be diagnosed with one or more lenticulostriate, basilar and/or other intracranial perforator aneurysms (starting from January 1st, 2013).
  • Patients aged ≥18 years
  • Written informed consent

Exclusion Criteria:

  • Presence of documented written or verbal refusal.
  • Aneurysm arising from the middle cerebral artery trunk which does not incorporate a lenticulostriate artery (Vargas Type 1), as they are not perforator aneurysms by strict definition.
  • Aneurysm arising from the basilar artery trunk adjacent to a perforating branch but not involving a perforating artery (Satti Type 1), as they are not perforator aneurysms by strict definition.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
mRS at 3 months after initial diagnosis of an intracranial perforator aneurysm
Time Frame: 90 days
90 days
mRS at last follow-up (including time-point of last follow-up after diagnosis)
Time Frame: Last follow-up, expected to be on average 2 years
Last follow-up, expected to be on average 2 years
Rupture/re-rupture of the index aneurysm as a time-event outcome
Time Frame: Date of rupture/re-rupture
Date of rupture/re-rupture
Death during the acute hospital stay
Time Frame: Until patient discharge, up to 4 weeks
Until patient discharge, up to 4 weeks
Death up to 90 days (related to the index aneurysm)
Time Frame: 90 days
90 days
Number of participants with ischemic stroke (imaging based)
Time Frame: Follow-up, expected to be up to 7 days
Follow-up, expected to be up to 7 days
Periprocedural and postprocedural complications in patients submitted to endovascular or surgical treatment
Time Frame: Peri-/postprocedural, expected to be up to 24 hours
Peri-/postprocedural, expected to be up to 24 hours
For patients receiving treatment, assessment of aneurysm occlusion after treatment and available follow-ups
Time Frame: First follow-up, expected to be within 7 days
First follow-up, expected to be within 7 days

Collaborators and Investigators

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

Sponsor

Insel Gruppe AG, University Hospital Bern

Investigators

  • Principal Investigator: Tomas Dobrocky, PD, MD, Institute of Diagnostic and Interventional Neuroradiology, Inselspital Bern
  • Principal Investigator: Johannes Kaesmacher, Prof, MD, PhD, Institute of Diagnostic and Interventional Neuroradiology, Inselspital Bern
  • Principal Investigator: Bettina L. Serrallach, MD, Institute of Diagnostic and Interventional Neuroradiology, Inselspital Bern

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)

November 9, 2023

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

December 4, 2023

First Submitted That Met QC Criteria

December 18, 2023

First Posted (Estimated)

January 3, 2024

Study Record Updates

Last Update Posted (Estimated)

January 3, 2024

Last Update Submitted That Met QC Criteria

December 18, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-01778

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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