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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04819074
Other study ID # PRAEMIUM
Secondary ID
Status Recruiting
Phase
First received
Last updated
Start date May 20, 2021
Est. completion date October 1, 2022

Study information

Verified date December 2021
Source University of Zurich
Contact Victor Staartjes
Phone +41 44 255 2660
Email praemium@usz.ch
Is FDA regulated No
Health authority
Study type Observational

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Recruiting
Enrollment 4000
Est. completion date October 1, 2022
Est. primary completion date January 1, 2022
Accepts healthy volunteers
Gender All
Age group 18 Years and older
Eligibility 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 Design


Related Conditions & MeSH terms


Intervention

Procedure:
Microsurgery
Microsurgery for unruptured intracranial aneurysm

Locations

Country Name City State
Australia Royal Melbourne Hospital Melbourne
Australia Macquarie University Sydney
Austria Innsbruck University Innsbruck
Austria Linz Kepler Klinikum Linz
Czechia Prague University Praha
Germany Charité Univesitätsmedizin Berlin
Germany Dresden Uniklinikum Dresden
Germany Düsseldorf Universitätsmedizin Düsseldorf
Germany Frankfurt University Frankfurt
Germany Universitätsmedizin Göttingen Göttingen
Germany University of Cologne Köln
Germany Unimedizin Mainz Mainz
Italy University of Florence - Careggi Florence
Italy University of Genoa Genoa
Italy University of Messina Messina
Italy Carlo Besta Milan
Italy Padova University Padova
Italy Gemelli University Hospital Roma
Italy Sapienza University Roma
Italy University of Verona Verona
Netherlands Amsterdam UMC Amsterdam
Netherlands Leiden University Leiden
Netherlands UMC Utrecht Utrecht
Russian Federation Burdenko Hospital Moscow
Sweden Sahlgrenska Hospital Göteborg
Switzerland Inselspital Bern Bern
Switzerland University Hospital Zurich Zürich
United States Emory University Hospital Atlanta Georgia
United States Brigham and Women's Hospital Boston Massachusetts
United States University of Illinois Chicago Illinois
United States UCLA Los Angeles California
United States University of Wisconsin Madison Wisconsin
United States North Shore University Hospital Manhasset New York
United States Barrow Neurological Institute Phoenix Arizona
United States Mayo Clinic Rochester Minnesota
United States UCSF San Francisco California
United States Stanford University Stanford California

Sponsors (37)

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

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Czechia,  Germany,  Italy,  Netherlands,  Russian Federation,  Sweden,  Switzerland, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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
Primary 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
Primary 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
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