Study to Evaluate Cerebral AneurysmFlow Results in Occlusion (CARO)

Multicenter Observational Cohort Study to Evaluate Cerebral AneurysmFlow Results in Occlusion

AneurysmFlow R1.0 is an approved (i.e. CE labeled, 510k, Health Canada), software tool intended to provide relevant information on the blood flow in a cerebral aneurysm and its parent artery based on angiography. It calculates the Mean Aneurysm Flow Amplitude (MAFA) ratio to measure the volumetric flow rate quotient before and after Flow Diverter Stent (FDS) implantation in the region of interest.

The current study is a prospective, single arm, observational, multicenter cohort study to assess the prognostic value of the MAFA ratio for predicting full aneurysm occlusion 12 months after flow diverter placement.

Study Overview

• Status: Completed
• Conditions: Intracranial Aneurysm
• Intervention / Treatment: Device: AneurysmFlow

Detailed Description

AneurysmFlow R1.0 is an approved (CE labeled, cleared in US, Canada and Argentina), software tool intended to provide relevant information on the blood flow in a cerebral aneurysm and its parent artery based on angiography. It provides color coded and vector field representation of a digital subtraction angiography (DSA). It can quantify blood flow rates in the artery based on DSA and 3-D Rotational Angiogram (3DRA) data. It can visualize blood flow patterns in an aneurysm based on DSA data. Specifically, it calculates the Mean Aneurysm Flow Amplitude (MAFA) ratio to measure the volumetric flow rate quotient before and after Flow Diverter Stent (FDS) implantation in the region of interest. It is manufactured by Philips Medical Systems bv., a Philips Healthcare company.

120 subjects with unruptured, >5mm saccular aneurysm(s) located in the anterior intracranial circulation and suitable for an endovascular treatment with a Flow Diverter Stent will be enrolled in the study. The enrollment period is expected to last for 1 year.

Physician investigators participating in this study are expected to follow their normal clinical practice in enrolling, treating and following patients with intracranial aneurysms that are amenable to treatment with flow diverter stents. No additional procedures are required of patients in order to participate in this observational study.

Pre-Screening

Patients presenting with intracranial saccular aneurysm(s) will be evaluated by the neuro interventional team, in accordance with institutional practice, to establish an appropriate treatment plan based on the patient's medical condition and available diagnostic screening procedures prior to recruitment in the study. More than one aneurysm in a single patient may be treated, but only one target aneurysm treated with an FDS device will be considered as part of this study. If treatment of the aneurysm with the FDS is deemed appropriate, the institution's guidelines regarding their ethics committee and informed consent process will be followed.

Screening

After obtaining the consent form(s) approved by the local research ethics board (REB), the principal investigator will screen the potential investigation subjects for the CARO study. The principal investigator or his delegates on the study team will enter data in a pre-designed digital Case Report Form (e-CRF). This will include patient demographics, relevant past medical and surgical history, and specific target aneurysm data along with pre-procedural/screening imaging details.

Only patients who meet all inclusion and none of the exclusion criteria will qualify for this study. The measurement and size of each aneurysm will be verified by the principal investigator. If the size of the aneurysm is acceptable, then it will be included in the study. It is recommended that this measurement should be done within 180 days before the procedure.

Index Procedure and Discharge

The investigator will proceed with standard of care procedures on the day of Index Procedure (i.e. FDS insertion) for the target aneurysm(s). Then, endovascular treatment procedure details should be provided for each eligible patient. Blood flow velocity will be calculated using the dedicated software AneurysmFlow (Philips Healthcare, Best, The Netherlands), which will be installed on standard of care imaging equipment. For this purpose, digital subtraction angiograms will be acquired during the procedure; just before and right after placement of the FDS. Calculation of blood flow velocity will be performed automatically on the AneurysmFlow software. There are no additional devices or medications required for the study. The AneurysmFlow software uses standard-of-care 2D DSA and 3D-RA image sequences to determine this flow information. All raw image sequences will be stored for future reference.

This study will not make any recommendation on patient management or on treatment strategy. Also, this software will not disrupt standard-of-care workflow for the interventionalist.

Follow-Ups (6 and 12 months)

All registry patients treated with FDS are expected to follow their routine post treatment clinical visits, which will include a standard-of-care head imaging (e.g. Computed Tomography Angiography (CTA), Magnetic Resonance Angiography (MRA) and/or DSA) test to classify aneurysm occlusion (i.e. Raymond-Roy Occlusion Classification I) at 6 months (±49 days) and 12 months (±49 days). During the 6 and 12 month follow up visits, patient medical charts will be accessed to collect adverse events (if applicable) and document any post-treatment neurological deterioration (neurological assessment, modified Rankin Scale). De-identified data (i.e. clinical notes, imaging reports etc.) will be entered in the relevant e-CRF sections. All (serious) adverse events (i.e. re-operations, ruptures and deaths) whether or not related to the investigational device will be collected and reported conform local rules and regulations.

The total duration of the study is expected to take approximately 2.5 years. Patient enrollment will take place between September 2018 and September 2019. Each subject will be in the study for 1 year (follow-up).

• Study Type: Observational
• Enrollment (Actual): 121

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1428 CABA
    • ENERI
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto Western Hospital
• United States
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Baptist Health
  • Massachusetts
    • Worcester, Massachusetts, United States, 01655
      • UMass Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with age 18 or older, of both genders and all races. Patients are considered to be enrolled in the study after they have signed the informed consent form.

Description

Inclusion Criteria:

• Subject with unruptured, ≥5mm saccular aneurysm(s) located in the anterior intracranial circulation and suitable for an endovascular treatment with a Flow Diverter Stent
• Subject is 18 years of age or older, or of legal age to give informed consent per state or national law.
• Subject is available for clinical follow-ups.

Exclusion Criteria:

• Non-saccular brain aneurysm(s) (i.e. dissecting, fusiform, atherosclerotic, mycotic, bifurcational). Prior aneurysm treatment with either endovascular (stenting, coiling) or surgical (clipping) techniques.
• Endovascular treatment assisted with coils or intracranial stents
• Significant or severe allergy to intra-arterial contrast medium uncontrolled by pre-procedure medications.
• Severe kidney disease (Glomerular Filtration Rate < 60).
• Subjects not willing (or able) to attend post FDS insertion standard-of-care follow up clinic visits requiring DSA, head MRI or CTA imaging.
• Subject participates in a potentially confounding drug or device trial during the course of the study.
• Subject meets an exclusion criteria according to national law (e.g. age, pregnant woman, breast feeding woman).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

AneurysmFlow Observational Cohort; Subjects with unruptured, >5mm saccular aneurysm(s) located in the anterior intracranial circulation and suitable for an endovascular treatment with a Flow Diverter Stent enrolled at the centers participating in this CARO study.

Device: AneurysmFlow; AneurysmFlow R1.0 is an approved (CE labeled, cleared in US, Canada and Argentina), software tool intended to provide relevant information on the blood flow in a cerebral aneurysm and its parent artery based on angiography. It provides color coded and vector field representation of a digital subtraction angiography (DSA). It can quantify blood flow rates in the artery based on DSA and 3-D Rotational Angiogram (3DRA) data. It can visualize blood flow patterns in an aneurysm based on DSA data. Specifically, it calculates the Mean Aneurysm Flow Amplitude (MAFA) ratio to measure the volumetric flow rate quotient before and after Flow Diverter Stent (FDS) implantation in the region of interest. It is manufactured by Philips Medical Systems B.V., a Philips Healthcare company.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prognostic value of the MAFA ratio with respect to full aneurysm occlusion within 12 months	To assess the prognostic value (i.e. c-statistic including confidence intervals) of the MAFA ratio with respect to full aneurysm occlusion (i.e. using the Raymond-Roy Occlusion Classification I on standard-of-care head imaging) 12 months after Flow Diverter Stent placement.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prognostic value of the MAFA ratio with respect to full aneurysm occlusion within 6 months	To assess the prognostic value (i.e. c-statistic including confidence intervals) of the MAFA ratio with respect to full aneurysm occlusion (i.e. using the Raymond-Roy Occlusion Classification I on standard-of-care head imaging) 6 months after Flow Diverter Stent placement.	6 months
Optimal MAFA threshold	To determine the optimal MAFA ratio threshold to predict full aneurysm occlusion within 12 months	12 months
Adverse events	To register (serious) adverse events (i.e. re-operations, ruptures and deaths).	12 months

Collaborators and Investigators

• Sponsor: Philips Clinical & Medical Affairs Global
• Investigators: Principal Investigator: Ricardo Hanel, MD, PhD, Baptist Medical Center Jacksonville

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2018
• Primary Completion (Actual): November 27, 2023
• Study Completion (Actual): November 27, 2023

Study Registration Dates

• First Submitted: September 6, 2018
• First Submitted That Met QC Criteria: September 6, 2018
• First Posted (Actual): September 10, 2018

Study Record Updates

• Last Update Posted (Estimated): January 8, 2024
• Last Update Submitted That Met QC Criteria: January 5, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Radiology; Aneurysm; Neurology; Interventional Neurology; AneurysmFlow
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Arterial Diseases; Aneurysm; Intracranial Aneurysm
• Other Study ID Numbers: XCY610-130253

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: Yes
• product manufactured in and exported from the U.S.: No