scholarly journals Statin treatment for unruptured intracranial aneurysms study: a study protocol for a double-blind, placebo-controlled trial

2020 ◽  
Vol 5 (4) ◽  
pp. 410-415 ◽  
Author(s):  
Wenqiang Li ◽  
Yisen Zhang ◽  
Zhongbin Tian ◽  
Wei Zhu ◽  
Jian Liu ◽  
...  
Keyword(s):  
Intracranial Aneurysms ◽  
Controlled Trial ◽  
Statin Treatment ◽  
Phase Iii ◽  
Related Factors ◽  
Double Blind ◽  
Aneurysm Wall ◽  
Unruptured Intracranial Aneurysms ◽  
Risk Of Rupture ◽  
Be The Change

Background and purposeA large proportion of patients with unruptured intracranial aneurysm (IA) are not suitable for surgical clipping and endovascular treatment. For these patients, anti-inflammatory medications are worth exploring due to inflammation of aneurysmal wall being a major factor in higher risk of rupture. Statin has been proven to reduce inflammation of atherosclerosis and maybe a suitable candidate. This study aimed to evaluate whether atorvastatin will reduce inflammatory of the aneurysm wall measured by the signal index of aneurysm wall enhancement.Methods and analysisThe Statin Treatment for UnruptureD Intracranial anEurysms Study is a single-centre, phase 2, randomised, controlled, double-blind clinical trial. 60 patients with unruptured IAs with aneurysm wall enhancement will be enrolled in Beijing Tiantan Hospital. The patients will be randomised to receive atorvastatin 20 mg or placebo orally per day for 12 months. The primary outcome will be the change in aneurysm wall enhancement measured by the signal index during the 12 months treatment with atorvastatin. The secondary study outcomes will be the change in aneurysm wall enhancement measured by the signal index at 3 months, the changes in aneurysmal morphology and inflammation-related factors (C reactive protein, tumour necrosis factor-α, interleukin-1β and interleukin-6) at 3 and 12 months. This study is the first to explore the role of atorvastatin in reducing inflammation in unruptured IA, which could lay the groundwork for future phase III trial.Ethics and disseminationBeijing Tiantan Hospital’s Ethics committee approved the research and written informed consents would be obtained from all participant or representative included in this study.Trial registration numberNCT04149483

scholarly journals Computational Fluid Dynamics in Unruptured Intracranial Aneurysms

2018 ◽  
Vol 32 (2) ◽  
pp. 332-339 ◽  
Author(s):  
Maruf Matmusaev ◽  
Yasuhiro Yamada ◽  
Tsukasa Kawase ◽  
Riki Tanaka ◽  
Miyatani Kyosuke ◽  
...  
Keyword(s):  
Fluid Dynamics ◽  
Computational Fluid Dynamics ◽  
Intracranial Aneurysms ◽  
Thin Wall ◽  
Rupture Risk ◽  
Ct Angiogram ◽  
Aneurysm Wall ◽  
Unruptured Intracranial Aneurysms ◽  
Increased Risk ◽  
Risk Of Rupture

Abstract Introduction and Objective: Intracranial aneurysm, also known as brain aneurysm, is a cerebrovascular disorder in which weakness in the wall of a cerebral artery causes a localized dilation or ballooning of the blood vessel. There is no objective way, device or tools, of predicting rupture of aneurysm so far. Computational fluid dynamics (CFDs) was proposed as a tool to identify the rupture risk. Purpose of study: To reveal the correlation of CFD findings with intraoperative microscopic findings and prove the relevance of CFDin the prediction of rupture risk and in the management of unruptured intracranial aneurysms. Subjects and Methods: A prospective cohort study was conducted inNeurosurgery department of Fujita Health University Banbuntane Hotokukai Hospital, Nagoya, Japanduring a 3‑month period in 2018,from January to March, Ten patientswere diagnosed unruptured intracranial aneurysms (UIA). In diagnosis computed tomography (CT) angiogram, CFD and digital subtraction angiogram were included. Intraoperatively microscopic examination of the aneurysm wall was carried out and images recorded. The correlation between microscopic dome morphology and CFD information was performed. Results: Nine cases were found intraoperatively to have a higher risk of rupture based on the thinning of the wall. One cases had an atherosclerotic wall. All cases had low wall shear stress (WSS). In 90 % of cases Low WSS was able to predict the potency rupture risk in the near future. Conclusions: This study of CFD and its correlation with intraoperativefindings of the aneurysm suggested that low WSS of the aneurysm wall is associated with thin wall aneurysm and hence increased risk of aneurysm rupture. Thus CFD can be used to predict the risk of rupture of unruptured aneurysm and for planning of its treatment.

Brivanib in Patients With Advanced Hepatocellular Carcinoma Who Were Intolerant to Sorafenib or for Whom Sorafenib Failed: Results From the Randomized Phase III BRISK-PS Study

2013 ◽  
Vol 31 (28) ◽  
pp. 3509-3516 ◽  
Author(s):  
Josep M. Llovet ◽  
Thomas Decaens ◽  
Jean-Luc Raoul ◽  
Eveline Boucher ◽  
Masatoshi Kudo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Controlled Trial ◽  
Objective Response ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Time To Progression ◽  
Fibroblast Growth Factor Receptors ◽  
Double Blind ◽  
Dual Inhibitor

Purpose Brivanib is a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor receptors implicated in tumorigenesis and angiogenesis in hepatocellular carcinoma (HCC). An unmet medical need persists for patients with HCC whose tumors do not respond to sorafenib or who cannot tolerate it. This multicenter, double-blind, randomized, placebo-controlled trial assessed brivanib in patients with HCC who had been treated with sorafenib. Patients and Methods In all, 395 patients with advanced HCC who progressed on/after or were intolerant to sorafenib were randomly assigned (2:1) to receive brivanib 800 mg orally once per day plus best supportive care (BSC) or placebo plus BSC. The primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response rate (ORR), and disease control rate based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) and safety. Results Median OS was 9.4 months for brivanib and 8.2 months for placebo (hazard ratio [HR], 0.89; 95.8% CI, 0.69 to 1.15; P = .3307). Adjusting treatment effect for baseline prognostic factors yielded an OS HR of 0.81 (95% CI, 0.63 to 1.04; P = .1044). Exploratory analyses showed a median time to progression of 4.2 months for brivanib and 2.7 months for placebo (HR, 0.56; 95% CI, 0.42 to 0.76; P < .001), and an mRECIST ORR of 10% for brivanib and 2% for placebo (odds ratio, 5.72). Study discontinuation due to treatment-related adverse events (AEs) occurred in 61 brivanib patients (23%) and nine placebo patients (7%). The most frequent treatment-related grade 3 to 4 AEs for brivanib included hypertension (17%), fatigue (13%), hyponatremia (11%), and decreased appetite (10%). Conclusion In patients with HCC who had been treated with sorafenib, brivanib did not significantly improve OS. The observed benefit in the secondary outcomes of TTP and ORR warrants further investigation.

scholarly journals Melatonin for prevention of postoperative delirium after lower limb fracture surgery in elderly patients (DELIRLESS): study protocol for a multicentre randomised controlled trial

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e053908
Author(s):  
Stéphanie Sigaut ◽  
Camille Couffignal ◽  
Marina Esposito-Farèse ◽  
Vincent Degos ◽  
Serge Molliex ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Lower Limb ◽  
Postoperative Delirium ◽  
Controlled Trial ◽  
Functional Decline ◽  
Assessment Method ◽  
Phase Iii ◽  
Double Blind ◽  
Prolonged Length ◽  
Surgery In Elderly

IntroductionPostoperative delirium (POD) is one of the most frequent complication after surgery in elderly patients, and is associated with increased morbidity and mortality, prolonged length of stay, cognitive and functional decline leading to loss of autonomy, and important additional healthcare costs. Perioperative inflammatory stress is a key element in POD genesis. Melatonin exhibits antioxidative and immune-modulatory proprieties that are promising concerning delirium prevention, but in perioperative context literature are scarce and conflicting. We hypothesise that perioperative melatonin can reduce the incidence of POD.Methods and analysisThe DELIRLESS trial is a prospective, national multicentric, phase III, superiority, comparative randomised (1:1) double-blind clinical trial. Among patients aged 70 or older, hospitalised and scheduled for surgery of a severe fracture of a lower limb, 718 will be randomly allocated to receive either melatonin 4 mg per os or placebo, every night from anaesthesiologist preoperative consultation and up to 5 days after surgery. The primary outcome is POD incidence measured by either the French validated translation of the Confusion Assessment Method (CAM) score for patients hospitalised in surgery, or CAM-ICU score for patients hospitalised in ICU (Intensive Care Unit). Daily delirium assessment will take place during 10 days after surgery, or until the end of hospital stay if it is shorter. POD cumulative incidence function will be compared at day 10 between the two randomised arms in a competing risks framework, using the Fine and Grey model with death as a competing risk of delirium.Ethics and disseminationThe DELIRLESS trial has been approved by an independent ethics committee the Comité de Protection des Personnes (CPP) Sud-Est (ref CPP2020-18-99 2019-003210-14) for all study centres. Participant recruitment begins in December 2020. Results will be published in international peer-reviewed medical journals.Trial registration numberNCT04335968, first posted 7 April 2020.Protocol version identifierN°3–0, 3 May 2021.

scholarly journals Semiautomated 3D mapping of aneurysmal wall enhancement with 7T-MRI

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ashrita Raghuram ◽  
Alberto Varon ◽  
Jorge A. Roa ◽  
Daizo Ishii ◽  
Yongjun Lu ◽  
...  
Keyword(s):  
Intracranial Aneurysms ◽  
3D Imaging ◽  
High Resolution Imaging ◽  
Biological Processes ◽  
Automated Method ◽  
Aneurysm Wall ◽  
Unruptured Intracranial Aneurysms ◽  
Potential Biomarker ◽  
Resolution Imaging ◽  
Objective Tool

AbstractAneurysm wall enhancement (AWE) after the administration of contrast gadolinium is a potential biomarker of unstable intracranial aneurysms. While most studies determine AWE subjectively, this study comprehensively quantified AWE in 3D imaging using a semi-automated method. Thirty patients with 33 unruptured intracranial aneurysms prospectively underwent high-resolution imaging with 7T-MRI. The signal intensity (SI) of the aneurysm wall was mapped and normalized to the pituitary stalk (PS) and corpus callosum (CC). The CC proved to be a more reliable normalizing structure in detecting contrast enhancement (p < 0.0001). 3D-heatmaps and histogram analysis of AWE were used to generate the following metrics: specific aneurysm wall enhancement (SAWE), general aneurysm wall enhancement (GAWE) and focal aneurysm wall enhancement (FAWE). GAWE was more accurate in detecting known morphological determinants of aneurysm instability such as size ≥ 7 mm (p = 0.049), size ratio (p = 0.01) and aspect ratio (p = 0.002). SAWE and FAWE were aneurysm specific metrics used to characterize enhancement patterns within the aneurysm wall and the distribution of enhancement along the aneurysm. Blebs were easily identified on 3D-heatmaps and were more enhancing than aneurysm sacs (p = 0.0017). 3D-AWE mapping may be a powerful objective tool in characterizing different biological processes of the aneurysm wall.

scholarly journals Long-term outcomes of coil embolization of unruptured intracranial aneurysms

2018 ◽  
Vol 129 (6) ◽  
pp. 1492-1498 ◽  
Author(s):  
Masaomi Koyanagi ◽  
Akira Ishii ◽  
Hirotoshi Imamura ◽  
Tetsu Satow ◽  
Kazumichi Yoshida ◽  
...  
Keyword(s):  
Coil Embolization ◽  
Intracranial Aneurysms ◽  
Additional Treatment ◽  
Long Term Outcomes ◽  
Unruptured Intracranial Aneurysms ◽  
Risk Of Rupture ◽  
Long Term Follow Up ◽  
Multiple Stroke

OBJECTIVELong-term follow-up results of the treatment of unruptured intracranial aneurysms (UIAs) by means of coil embolization remain unclear. The aim of this study was to analyze the frequency of rupture, retreatment, stroke, and death in patients with coiled UIAs who were followed for up to 20 years at multiple stroke centers.METHODSThe authors retrospectively analyzed data from cases in which patients underwent coil embolization between 1995 and 2004 at 4 stroke centers. In collecting the late (≥ 1 year) follow-up data, postal questionnaires were used to assess whether patients had experienced rupture or retreatment of a coiled aneurysm or any stroke or had died.RESULTSOverall, 184 patients with 188 UIAs were included. The median follow-up period was 12 years (interquartile range 11–13 years, maximum 20 years). A total of 152 UIAs (81%) were followed for more than 10 years. The incidence of rupture was 2 in 2122 aneurysm-years (annual rupture rate 0.09%). Nine of the 188 patients with coiled UIAs (4.8%) underwent additional treatment. In 5 of these 9 cases, the first retreatment was performed more than 5 years after the initial treatment. Large aneurysms were significantly more likely to require retreatment. Nine strokes occurred over the 2122 aneurysm-years. Seventeen patients died in this cohort.CONCLUSIONSThis study demonstrates a low risk of rupture of coiled UIAs with long-term follow-up periods of up to 20 years. This suggests that coiling of UIAs could prevent rupture for a long period of time. However, large aneurysms might need to be followed for a longer time.

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