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

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ClinicalTrials.gov Identifier: NCT04819074
Recruitment Status : Not yet recruiting
First Posted : March 26, 2021
Last Update Posted : April 29, 2021
Sponsor:
Collaborators:
Macquarie University, Australia
University of Melbourne
Kepler University Hospital
Medical University Innsbruck
General University Hospital, Prague
Universitätsklinikum Köln
University Hospital, Frankfurt
University Medical Center Mainz
University of Göttingen
University Hospital Dresden
Charite University, Berlin, Germany
Heinrich-Heine University, Duesseldorf
University of Roma La Sapienza
University of Padova
University of Florence
Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
University of Messina
Universita di Verona
Uniuversity of Genua, Italy
Leiden University Medical Center
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
UMC Utrecht
Burdenko Neurosurgery Institute
Sahlgrenska University Hospital, Sweden
University of Bern
Barrow Neurological Institute
Stanford University
Emory University
University of Wisconsin, Madison
University of California, San Francisco
University of Illinois at Chicago
Brigham and Women's Hospital
Mayo Clinic
University of California, Los Angeles
NorthShore University HealthSystem
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Information provided by (Responsible Party):
University of Zurich

Tracking Information
First Submitted Date March 18, 2021
First Posted Date March 26, 2021
Last Update Posted Date April 29, 2021
Estimated Study Start Date May 20, 2021
Estimated Primary Completion Date August 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: March 25, 2021)
  • modified Rankin Scale [ Time Frame: Within 24 hours of admission to discharge, assessed up to 30 days ]
    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.
  • Sensorimotor neurological deficits [ Time Frame: Within 24 hours of admission to discharge, assessed up to 30 days ]
    Any new sensorimotor neurological deficits after surgery will be captured.
  • Clavien Dindo Complication Grading [ Time Frame: Within 24 hours of admission to discharge, assessed up to 30 days ]
    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.
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Prediction of Outcomes After Surgery for Unruptured Intracranial Aneurysms
Official Title The Prediction of Adverse Events After Microsurgery for Intracranial Unruptured Aneurysms (PRAEMIUM) Study
Brief Summary 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.
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
Study Design Observational Model: Cohort
Time Perspective: Retrospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
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.
Condition Aneurysm, Brain
Intervention Procedure: Microsurgery
Microsurgery for unruptured intracranial aneurysm
Study Groups/Cohorts 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.

Intervention: Procedure: Microsurgery
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Not yet recruiting
Estimated Enrollment
 (submitted: March 25, 2021)
4000
Original Estimated Enrollment Same as current
Estimated Study Completion Date August 1, 2021
Estimated Primary Completion Date August 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria

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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Not Provided
Contacts
Contact: Victor Staartjes +41 44 255 2660 praemium@usz.ch
Listed Location Countries Australia,   Austria,   Czechia,   Germany,   Italy,   Netherlands,   Russian Federation,   Sweden,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number NCT04819074
Other Study ID Numbers PRAEMIUM
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party University of Zurich
Study Sponsor University of Zurich
Collaborators
  • Macquarie University, Australia
  • University of Melbourne
  • Kepler University Hospital
  • Medical University Innsbruck
  • General University Hospital, Prague
  • Universitätsklinikum Köln
  • University Hospital, Frankfurt
  • University Medical Center Mainz
  • University of Göttingen
  • University Hospital Dresden
  • Charite University, Berlin, Germany
  • Heinrich-Heine University, Duesseldorf
  • University of Roma La Sapienza
  • University of Padova
  • University of Florence
  • Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta
  • University of Messina
  • Universita di Verona
  • Uniuversity of Genua, Italy
  • Leiden University Medical Center
  • Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
  • UMC Utrecht
  • Burdenko Neurosurgery Institute
  • Sahlgrenska University Hospital, Sweden
  • University of Bern
  • Barrow Neurological Institute
  • Stanford University
  • Emory University
  • University of Wisconsin, Madison
  • University of California, San Francisco
  • University of Illinois at Chicago
  • Brigham and Women's Hospital
  • Mayo Clinic
  • University of California, Los Angeles
  • NorthShore University HealthSystem
  • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Investigators
Principal Investigator: Victor Staartjes USZ
Principal Investigator: Giuseppe Esposito USZ
PRS Account University of Zurich
Verification Date April 2021