- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02066493
Giant Intracranial Aneurysm Registry
Study Overview
Status
Conditions
Detailed Description
Definition of aims, eligibility of patients and data flow
In August 2009 a steering committee was appointed and its first meeting took place in Berlin. Here the aims of the registry were defined as follows: 1) To generate detailed insight into which therapies are being conducted. 2) To document the natural history of patients and follow it over years after diagnosis. 3) To follow imaging data of giant aneurysms over years after diagnosis, whether treated conservatively or not. 4) To expand the register into several disciplines (by inviting neuroradiologic and neurologic centers to join) and internationally.
Inclusion criteria are a) the diagnosis of a giant intracranial aneurysm by CT, MRI or regular angiography, b) age 18 years and older and c) informed consent. There are no exclusion criteria. If a patient is not able to give informed consent due to his or her clinical situation, the legal representative of the patient (e.g. family member) will be informed and asked to sign the consent form on behalf of the patient.
Patients are recruited consecutively in responsibility of each center. In addition to the prospective part there is a retrospective part in which patients are included that were admitted after January 2006. Data are gathered at admission, discharge and 1/3/5 years after discharge. Starting from February 2010 a 9-month pilot phase was conducted in order to identify and correct possible problems of data acquisition.
Development of a study protocol
Relevant variables were discussed on the basis of existing literature on giant intracranial aneurysms. All variables were chosen so that they can be determined in a routine clinical context even in small centers with minimal technical equipment. Data collection was decided to be carried out using a modular structure, consisting of a basic module and additional modules for specific research questions.
The steering committee decided on the content of a mandatory basic data collection for all centers. This basic module was designed to keep the amount of variables at a minimum so that data collection can be conducted as safely and quickly as possible by physicians of all disciplines. It focuses on the clinical course between initial presentation and discharge but also includes data on patient history, such as risk factors and possible prior aneurysm therapy. A neurological examination of cranial nerve functions, motor capability and speech is conducted initially, at discharge and during 3 mandatory follow-up examinations. At each examination the patients' physical condition is recorded using internationally accepted and reliable grading systems. The investigator is asked to not only record a clinical diagnosis, such as epileptic seizure or incidental finding, but also use imaging data to produce a radiological diagnosis and characterize the aneurysm regarding its location, size, shape and structure. The mode of therapy is documented choosing between conservative, surgical and endovascular options and combinations thereof. Possible complications are recorded as well as radiologic results of intervention.
Each center is given the option to take part in additional extra modules, which serve as a basis for spin-off projects resulting from the discussion within the study group. This comprises for example an imaging module to lead to a better understanding of how giant intracranial aneurysms develop over time. It will monitor changes in aneurysm configuration and flow dynamics using 3D-imaging data. A cost module will integrate data on treatment expenses making it possible to compare the costs of each mode of therapy.
An external review of the study protocol was conducted to ensure high methodological quality and wide acceptance of the results. For this purpose a preliminary working report was forwarded to 4 independent experts in the field of neurovascular research. The reviewers were asked to comment on the appropriateness of the methods, the practicability of our variables and the coverage of relevant aspects of giant intracranial aneurysm care. The comments of the external reviewers were gathered and discussed within the steering committee. Based on the recommendations of the external reviewers, a final revision of the study protocol took place.
Primary hypothesis, study outcome and statistical analyses
The primary hypothesis of the study is that conservative, endovascular and surgical therapy result in equal aneurysm rupture rates. Therefore primary outcome will be aneurysm rupture rate at 5 years of follow up.
The sample size calculation is based on the estimated 5-year cumulative rupture rates for patients with unruptured giant aneurysm given in the ISUIA-Trial. According to their results we assume a 5-year rupture rate of 0.30 irrespective of which specific treatment is applied. Because of a lack of data on special rupture rates regarding patients treated with the three considered methods, sample size calculation was done for one proportion based on precision analysis. Consequently, a two-sided 95% confidence interval with a width equal to 0.10 is achieved by a sample size of 320 patients. For the outcomes death or rupture the corresponding survival functions with 95% confidence intervals will be estimated by the Kaplan-Meier method. The null-hypotheses of equal survival curves for two treatment groups will be tested by the Log-Rank test. With documented dates of rupture events the sample size of 320 calculated above is sufficient to detect moderate effects of possible predictors for rupture by Cox proportional hazards regression within a secondary analysis. Furthermore we can model the logit of rupture after 5 years by binary logistic regression detecting possible moderate to considerable effects of predictors. Therapy (conventional, surgery or endovascular) will be the main factor of interest for both multivariable analyses.
Patient recruitment / Data storage / Quality assurance
In 2008 patient recruitment began at the Charité Berlin, one year later data from other centers were included as well, initially only in Germany, later on throughout Europe and Japan. Patient data are stored using pseudonyms. Centers can either use a fax-based data inclusion form or a web-based entry form. All data are stored at the Charité - Berlin. For quality assurance a monitoring visit to the 7 most-including centers was conducted in 2013.
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
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Vienna, Austria
- Department of Neurosurgery, Medical University Vienna
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Helsinki, Finland
- Department of Neurosurgery, Helsinki University Central
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Toulouse, France
- Department of Neuroradiology, University Hospital
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Berlin, Germany
- Department of Neurology - Charité Berlin
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Berlin, Germany
- Department of Neurosurgery, Charité Berlin
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Deggendorf, Germany
- Department of Neurosurgery and Neuroradiology, Klinikum Deggendorf
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Freiburg, Germany
- Department of Neurosurgery, University of Freiburg
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Greifswald, Germany
- Department of Neurosurgery - University of Greifswald
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Göttingen, Germany
- Department of Neurosurgery - University of Goettingen
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Hamburg, Germany
- Department of Neurosurgery - University of Hamburg
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Jena, Germany
- Department of Neurosurgery, Friedrich-Schiller-University
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Leipzig, Germany
- Department of Neuroradiology, University of Leipzig
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Munich, Germany
- Department of Neurosurgery - Technical University of Munich
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Regensburg, Germany
- Department of Neurosurgery - University of Regensburg
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Wuerzburg, Germany
- Institut für Klinische Epidemiologie und Biometrie der Universität Wuerzburg
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Milano, Italy
- Department of Neuroradiology, Ospedale Niguarda Ca' Granda
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Tokio, Japan
- Department of Neurosurgery, Jikei University
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Utrecht, Netherlands
- Department of Neurosurgery, University Hospital
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Moscow, Russian Federation
- Department of Neurosurgery, Burdenko Neurosurgical Institute
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Aarau, Switzerland
- Department of Neurosurgery, Kantonsspital Aarau
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Geneva, Switzerland
- Department of Neurosurgery - University of Geneva
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Zurich, Switzerland
- Department of Neuroradiology - Klinikum Hirslanden
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Zurich, Switzerland
- Department of Neurosurgery, University Hospital of Zurich
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- diagnosis of a giant intracranial aneurysm
Exclusion Criteria:
- age younger than 18
Study Plan
How is the study designed?
Design Details
- Observational Models: Cohort
- Time Perspectives: Prospective
Cohorts and Interventions
Group / Cohort |
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conservative management
neither surgical nor endovascular management
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endovascular management
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surgical management
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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aneurysm rupture rate - diagnosed radiologically (e.g. by CT) or clinically
Time Frame: 5 years
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5 years
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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health status of the patient quantified by modified Rankin Scale in combination with a basic neurological exam
Time Frame: 5 years
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5 years
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Julius Dengler, MD, Charite University, Berlin, Germany
- Study Director: Peter Vajkoczy, Prof., MD, Charite University, Berlin, Germany
- Study Director: Veit Rohde, Prof., MD, University of Goettingen
- Study Director: Peter Heuschmann, Prof., MD, University of Wuerzburg
- Study Director: Bernhard Meyer, Prof., MD, Technical University of Munich
- Study Director: Daniel Ruefenacht, Prof., MD, Klinikum Hirslanden Zurich
- Study Director: Matthias Endres, Prof., MD, Charite University, Berlin, Germany
Publications and helpful links
General Publications
- Dengler J, Heuschmann PU, Endres M, Meyer B, Rohde V, Rufenacht DA, Vajkoczy P; Giant Intracranial Aneurysm Study Group. The rationale and design of the Giant Intracranial Aneurysm Registry: a retrospective and prospective study. Int J Stroke. 2011 Jun;6(3):266-70. doi: 10.1111/j.1747-4949.2011.00588.x. Epub 2011 Apr 7.
- Dengler J, Rufenacht D, Meyer B, Rohde V, Endres M, Lenga P, Uttinger K, Rucker V, Wostrack M, Kursumovic A, Hong B, Mielke D, Schmidt NO, Burkhardt JK, Bijlenga P, Boccardi E, Cognard C, Heuschmann PU, Vajkoczy P; Giant Intracranial Aneurysm Study Group. Giant intracranial aneurysms: natural history and 1-year case fatality after endovascular or surgical treatment. J Neurosurg. 2019 Dec 6;134(1):49-57. doi: 10.3171/2019.8.JNS183078.
- Haemmerli J, Lenga P, Hong B, Kursumovic A, Maldaner N, Burkhardt JK, Bijlenga P, Rufenacht DA, Schmidt NO, Vajkoczy P, Dengler J. Clinical implications and radiographic characteristics of the relation between giant intracranial aneurysms of the posterior circulation and the brainstem. Acta Neurochir (Wien). 2019 Sep;161(9):1747-1753. doi: 10.1007/s00701-019-04016-x. Epub 2019 Jul 29.
- Lenga P, Hohaus C, Hong B, Kursumovic A, Maldaner N, Burkhardt JK, Bijlenga P, Rufenacht DA, Schmidt NO, Vajkoczy P, Dengler J. Giant intracranial aneurysms of the posterior circulation and their relation to the brainstem: analysis of risk factors for neurological deficits. J Neurosurg. 2018 Aug 10;131(2):403-409. doi: 10.3171/2018.4.JNS172343.
- Durner G, Piano M, Lenga P, Mielke D, Hohaus C, Guhl S, Maldaner N, Burkhardt JK, Pedro MT, Lehmberg J, Rufenacht D, Bijlenga P, Etminan N, Krauss JK, Boccardi E, Hanggi D, Vajkoczy P, Dengler J; Giant Intracranial Aneurysm Study Group. Cranial nerve deficits in giant cavernous carotid aneurysms and their relation to aneurysm morphology and location. Acta Neurochir (Wien). 2018 Aug;160(8):1653-1660. doi: 10.1007/s00701-018-3580-2. Epub 2018 Jun 9.
- Maldaner N, Guhl S, Mielke D, Musahl C, Schmidt NO, Wostrack M, Rufenacht DA, Vajkoczy P, Dengler J; Giant Intracranial Aneurysm Study Group. Changes in volume of giant intracranial aneurysms treated by surgical strategies other than direct clipping. Acta Neurochir (Wien). 2015 Jul;157(7):1117-23; discussion 1123. doi: 10.1007/s00701-015-2448-y. Epub 2015 May 23.
- Dengler J, Maldaner N, Bijlenga P, Burkhardt JK, Graewe A, Guhl S, Hong B, Hohaus C, Kursumovic A, Mielke D, Schebesch KM, Wostrack M, Rufenacht D, Vajkoczy P, Schmidt NO; Giant Intracranial Aneurysm Study Group. Perianeurysmal edema in giant intracranial aneurysms in relation to aneurysm location, size, and partial thrombosis. J Neurosurg. 2015 Aug;123(2):446-52. doi: 10.3171/2014.10.JNS141560. Epub 2015 Apr 17. Erratum In: J Neurosurg. 2015 Aug;123(2):478.
- Dengler J, Maldaner N, Bijlenga P, Burkhardt JK, Graewe A, Guhl S, Nakamura M, Hohaus C, Kursumovic A, Schmidt NO, Schebesch KM, Wostrack M, Vajkoczy P, Mielke D; Giant Intracranial Aneurysm Study Group. Quantifying unruptured giant intracranial aneurysms by measuring diameter and volume--a comparative analysis of 69 cases. Acta Neurochir (Wien). 2015 Mar;157(3):361-8; discussion 368. doi: 10.1007/s00701-014-2292-5. Epub 2014 Dec 12.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- Giant
- CS-2009-13 (Other Grant/Funding Number: Center for Stroke Research - Berlin)
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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