Prediction of Outcomes After Surgery for Unruptured Intracranial Aneurysms (PRAEMIUM)

The Prediction of Adverse Events After Microsurgery for Intracranial Unruptured Aneurysms (PRAEMIUM) Study

Accurate preoperative identification of patients at high risk for adverse outcomes would be clinically advantageous, as it would allow enhanced resource preparation, better surgical decision-making, enhanced patient education and informed consent, and potentially even modification of certain modifiable risk factors. The aim of the Prediction of adverse events after microsurgery for intracranial unruptured aneurysms (PRAEMIUM) study is therefore to develop and externally validate a clinically applicable, robust ML-based prediction tool based on multicenter data from a range of international centers.

Study Overview

• Status: Recruiting
• Conditions: Aneurysm, Brain
• Intervention / Treatment: Procedure: Microsurgery

Detailed Description

Introduction Unruptured intracranial aneurysms (UIAs) are incidentally detected at an increasing rate, mostly owing to the rise in availability of non-invasive cranial imaging. Decision-making in UIAs is complex and requires consideration of many risk factors for aneurysm growth and rupture to balance the benefits and risks of treatment versus observation. This is due to: 1) the high morbidity and case fatality inherent to aneurysmal subarachnoid hemorrhage (SAH) 2) the relatively low rupture rate of unruptured aneurysms; 3) the potential morbidity and mortality rate associated with either microsurgical or endovascular treatment.

Some consistent risk factors for rupture have been identified, including involvement of the posterior circulation, larger diameter, higher age, and some specific populations such as Japanese and Finnish patients. Many other risk factors have been suggested based on varying levels of evidence. However, it is difficult to integrate this considerable number of factors into a single risk assessment and to present a clear clinical decision making algorithm to patients. A range of scoring systems have been developed and validated to approximate the risk of rupture (PHASES) and growth (ELAPSS) or to balance the risks and benefits of microsurgical treatment versus follow-up imaging directly (UIATS) by integrating some of these risk factors. Still, these scores are focused on predicting rupture events instead of neurological outcome. In addition, they usually are focused on solely one outcome, instead of providing a wide range of objective predictive analytics that may then improve shared decision-making.

Machine learning (ML) methods have been extraordinarily effective at integrating many clinical patient variables into one holistic risk prediction tailored to each patient. A previous pilot study has been carried out to assess the feasibility of predicting surgical outcomes after surgery for UIAs in a small single-center sample, and it was found that prediction was feasible with good performance metrics, and the most important factors to be included in such models were also identified. A robust, multicenter, externally validated prediction model or predictive score for surgical outcome after microsurgery for UIAs does not yet exist.

Methods Data will be collected by a range of international centers. Overall, the model will be built and publication will be compiled according to the transparent reporting of a multivariable prediction model for individual prognosis or diagnosis (TRIPOD) guidelines.

Each center will collect their data either retrospectively, or from a prospective registry, or from a prospective registry supplemented by retrospectively collected variables. Data from patients operated from January 1st 2010 and onwards will be eligible for inclusion. Data collection should be completed, and deidentified data should be sent to the sponsor institution.

A standardized Excel spreadsheet will be provided by the sponsor. The data will be entered in standardized and anonymized form. This spreadsheet will only contain a study-specific patient number. The data set is anonymized source data that includes clinical data extracted from electronic health records (retrospectively or from a prospective registry of already existing data). The data will be anonymized upon entering them into the PRAEMIUM Excel spreadsheet, after which the patients will be numbered consecutively and there will be no way to trace the data back to individual patients. No identifiable data such as date of birth will be included. Whenever the PRAEMIUM Excel spreadsheet is transferred, it will be encrypted using a password and sent through a secure institutional e-mail server. The password will be sent in a separate e-mail. Some missing data is acceptable, but should be kept to a minimum (i.e. must be < 10%)

Endpoint Definitions Models will be developed for the following three endpoints at discharge: Poor neurological outcome (1), as well as presence of (2) new sensorimotor neurological deficits and (3) any complications (surgical or non-surgical). Neurological outcome was assessed by the modified Rankin scale (mRS), and a favorable neurological outcome was defined as mRS 0, 1, or 2. Complications will be assessed using the modified 2009 Clavien-Dindo grading (CDG), and occurrence of a complication was defined as any deviation from CDG 0.The Clavien-Dindo grading system is a classification of surgical complications: Grad 0 signifying no complication, Grade I identifying complications with any deviation from the normal intra- or postoperative course requiring medical treatment, and so forth. Detailed definitions are provided in the Excel spreadsheet. Surgery-related as well as none-surgery-related complications are counted. In case of multiple complications, only the complication with the highest CDG was counted per patient.

Input Feature Definitions All features are measured preoperatively. Recorded baseline variables will include age, gender, maximum aneurysm diameter, anatomical location (artery), total number of aneurysms per patient, if multiple aneurysms were treated during the index session, calcification of the aneurysm wall or neck, aneurysm morphology (saccular, dissecting, fusiform, or other), involvement of critical perforating or branch vessels, and intraluminal thrombosis.

In addition, the investigators will capture prior SAH, mRS at admission, prior aneurysm treatment, presence of anticoagulation/antiplatelet therapy preoperatively, and hypertension, as well as American Society of Anesthesiologists (ASA) grading, the PHASES, ELAPSS, and UIATS scores including the UIATS "pro-repair" and "pro-conservative treatment" subscores. The unruptured intracranial aneurysm treatment score (UIATS) consists of two subscores: One that represents the strength of recommendation for invasive repair of an unruptured aneurysm, and one that represents the strength of recommendation for conservative management of an unruptured aneurysm. The final overall UIATS score is subsequently calculated as the difference between the two subscores. Also included was the surgical approach: minimally invasive or standard approach, and whether a bypass was performed.

• Study Type: Observational
• Enrollment (Anticipated): 4000

Contacts and Locations

• Study Contact: Name: Victor Staartjes; Phone Number: +41 44 255 2660; Email: praemium@usz.ch

Study Locations

• Australia
  • Melbourne, Australia
    • Not yet recruiting
    • Royal Melbourne Hospital
    • Contact: Kate Drummond
  • Sydney, Australia
    • Not yet recruiting
    • Macquarie University
    • Contact: Antonio Di Ieva
• Austria
  • Innsbruck, Austria
    • Not yet recruiting
    • Innsbruck University
    • Contact: Claudius Thomé
  • Linz, Austria
    • Not yet recruiting
    • Linz Kepler Klinikum
    • Contact: Andreas Gruber
• Czechia
  • Praha, Czechia
    • Not yet recruiting
    • Prague University
    • Contact: Vladimir Benes
• Germany
  • Berlin, Germany
    • Not yet recruiting
    • Charité Univesitätsmedizin
    • Contact: Peter Vajkoczy
  • Dresden, Germany
    • Not yet recruiting
    • Dresden Uniklinikum
    • Contact: Gabriele Schackert
  • Düsseldorf, Germany
    • Not yet recruiting
    • Düsseldorf Universitätsmedizin
    • Contact: Daniel Hänggi
  • Frankfurt, Germany
    • Not yet recruiting
    • Frankfurt University
    • Contact: Volker Seifert
  • Göttingen, Germany
    • Not yet recruiting
    • Universitätsmedizin Göttingen
    • Contact: Veit Rohde
  • Köln, Germany
    • Not yet recruiting
    • University of Cologne
    • Contact: Roland Goldbrunner
  • Mainz, Germany
    • Not yet recruiting
    • Unimedizin Mainz
    • Contact: Florian Ringel
• Italy
  • Florence, Italy
    • Not yet recruiting
    • University of Florence - Careggi
    • Contact: Alessandro Della Puppa
  • Genoa, Italy
    • Not yet recruiting
    • University of Genoa
    • Contact: Gianluigi Zona
  • Messina, Italy
    • Not yet recruiting
    • University of Messina
    • Contact: Antonino Germano
  • Milan, Italy
    • Not yet recruiting
    • Carlo Besta
    • Contact: Paolo Ferroli
  • Padova, Italy
    • Not yet recruiting
    • Padova University
    • Contact: Domenico D'Avella
  • Roma, Italy
    • Not yet recruiting
    • Gemelli University Hospital
    • Contact: Alessandro Olivi
  • Roma, Italy
    • Not yet recruiting
    • Sapienza University
    • Contact: Antonio Santoro
  • Verona, Italy
    • Not yet recruiting
    • University of Verona
    • Contact: Giampietro Pinna
• Netherlands
  • Amsterdam, Netherlands
    • Not yet recruiting
    • Amsterdam UMC
    • Contact: W. Peter Vandertop
  • Leiden, Netherlands
    • Not yet recruiting
    • Leiden University
    • Contact: Wilco C Peul
  • Utrecht, Netherlands
    • Not yet recruiting
    • UMC Utrecht
    • Contact: Albert van der Zwan
• Russian Federation
  • Moscow, Russian Federation
    • Not yet recruiting
    • Burdenko Hospital
    • Contact: Eliava Shalva
• Sweden
  • Göteborg, Sweden
    • Not yet recruiting
    • Sahlgrenska Hospital
    • Contact: Asgeir Jakola
• Switzerland
  • Bern, Switzerland
    • Not yet recruiting
    • Inselspital Bern
    • Contact: Andreas Raabe
  • Zürich, Switzerland
    • Recruiting
    • University Hospital Zurich
    • Contact: Victor Staartjes
    • Contact: Giuseppe Esposito
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Not yet recruiting
      • Barrow Neurological Institute
      • Contact: Michael Lawton
  • California
    • Los Angeles, California, United States, 90095
      • Not yet recruiting
      • UCLA
      • Contact: Linda Liau
    • San Francisco, California, United States, 94143
      • Not yet recruiting
      • UCSF
      • Contact: Mitchel S Berger
    • Stanford, California, United States, 94305
      • Not yet recruiting
      • Stanford University
      • Contact: Gary K Steinberg
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Not yet recruiting
      • Emory University Hospital
      • Contact: Daniel Barrow
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Not yet recruiting
      • University of Illinois
      • Contact: Fady Charbel
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Not yet recruiting
      • Brigham and Women's Hospital
      • Contact: Antonio Chiocca
  • Minnesota
    • Rochester, Minnesota, United States, 55902
      • Not yet recruiting
      • Mayo Clinic
      • Contact: Giuseppe Lanzino
  • New York
    • Manhasset, New York, United States, 11030
      • Not yet recruiting
      • North Shore University Hospital
      • Contact: Amir Dehdashti
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Not yet recruiting
      • University of Wisconsin
      • Contact: Mustafa K Baskaya

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

We will include all adult patients (18 years or older) undergoing microsurgical treatment for UIAs. No specific exclusion criteria will be set. Patients with prior SAH may only be included when surgical treatment occurred at least 4 weeks after ictus. Only patients treated from January 1st 2010 onwards can be included in this study.

Description

Inclusion Criteria:

• Adult patients (18 or older)
• Undergone microsurgical treatment for unruptured intracranial aneurysm
• Patients with prior SAH may only be included when surgical treatment occurred at least 4 weeks after ictus.
• Treated from January 1st 2010 onwards

Exclusion Criteria:

• No specific exclusion criteria

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Patients with unruptured brain aneurysms; We will include all adult patients (18 years or older) undergoing microsurgical treatment for UIAs. No specific exclusion criteria will be set. Patients with prior SAH may only be included when surgical treatment occurred at least 4 weeks after ictus. Only patients treated from January 1st 2010 onwards can be included in this study. No intervention.	Procedure: Microsurgery; Microsurgery for unruptured intracranial aneurysm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified Rankin Scale	Neurological outcome was assessed by the modified Rankin scale (mRS), and a favorable neurological outcome was defined as mRS 0, 1, or 2. The scale runs from 0 to 5, and higher scores mean a worse outcome.	Within 24 hours of admission to discharge, assessed up to 30 days
Sensorimotor neurological deficits	Any new sensorimotor neurological deficits after surgery will be captured.	Within 24 hours of admission to discharge, assessed up to 30 days
Clavien Dindo Complication Grading	Complications will be assessed using the modified 2009 Clavien-Dindo grading (CDG), and occurrence of a complication was defined as any deviation from CDG 0. The CDG runs from 0 to 5, and higher scores mean a worse complication.	Within 24 hours of admission to discharge, assessed up to 30 days

Collaborators and Investigators

• Sponsor: University of Zurich
• Collaborators: Mayo Clinic; Fondazione Policlinico Universitario Agostino Gemelli IRCCS; University of California, Los Angeles; Charite University, Berlin, Germany; University of Roma La Sapienza; University of Wisconsin, Madison; Universita di Verona; University of Illinois at Chicago; Emory University; Brigham and Women's Hospital; UMC Utrecht; University of California, San Francisco; Stanford University; University of Padova; Heinrich-Heine University, Duesseldorf; Sahlgrenska University Hospital, Sweden; Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); University of Bern; Medical University Innsbruck; NorthShore University HealthSystem; Leiden University Medical Center; University of Messina; University of Florence; University of Melbourne; General University Hospital, Prague; University of Göttingen; Burdenko Neurosurgery Institute; Universitätsklinikum Köln; Barrow Neurological Institute; Macquarie University, Australia; University Hospital Dresden; University Hospital Frankfurt; Kepler University Hospital; Uniuversity of Genua, Italy; University Medical Center Mainz
• Investigators: Principal Investigator: Victor Staartjes, USZ; Principal Investigator: Giuseppe Esposito, USZ

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2021
• Primary Completion (Anticipated): January 1, 2022
• Study Completion (Anticipated): October 1, 2022

Study Registration Dates

• First Submitted: March 18, 2021
• First Submitted That Met QC Criteria: March 25, 2021
• First Posted (Actual): March 26, 2021

Study Record Updates

• Last Update Posted (Actual): December 21, 2021
• Last Update Submitted That Met QC Criteria: December 5, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: machine learning; unruptured aneurysm
• 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: PRAEMIUM

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