scholarly journals Prevalence, predictors and outcome of carotid stenosis. A sub study in the Preventive Antibiotics in Stroke Study (PASS)

2020 ◽  
Author(s):  
Twan van Velzen ◽  
Laurien Kuhrij ◽  
Willeke Westendorp ◽  
Diederik van de Beek ◽  
Paul Nederkoorn
Keyword(s):  
Carotid Artery ◽  
Diagnostic Testing ◽  
Phase Iii ◽  
Significant Shift ◽  
Open Label ◽  
Anterior Circulation ◽  
Unique Identifier ◽  
Clinical Trial Registration ◽  
Stroke Study ◽  
Date Estimate

Abstract Background:The prevalence of carotid artery stenosis (CAS) in acute ischaemic stroke (AIS) patients is historically reported at 15-20%, but an up-to-date estimate is lacking. We hypothesise it is lower than historically reported, due to better risk management to date. The study aims to study prevalence, predictors and survival of CAS in AIS patients. Methods:We included patients with AIS from the Preventive Antibiotics in Stroke Study (PASS), a large Dutch randomized, multicentre, open-label phase III trial that included 2538 patients with acute stroke and randomised between standard care or preventive ceftriaxone. Patients with stroke in the anterior circulation that underwent diagnostic testing of the internal carotid artery (ICA) were eligible for this sub study and used in these secondary analyses. Logistic regression analyses were performed to identify predictors for CAS ≥50%. Additionally, an ordinal regression was performed to assess the association between presence of CAS at baseline and functional outcome at three months on the modified Rankin scale (mRS). Results:1480 patients with AIS were included; 277 had CAS (18.7%; 95%CI:17.7-19.7). Age, hypertension, smoking and male gender were found as best-fit predictors for presence of CAS. Significant shift in mRS score after 90 days for CAS ≥50% towards a higher mRS score with an OR of 1.66 (95% CI 1.30-2.10) was found.Conclusions:Current prevalence of CAS is 18.7%, which is higher than we expected. Gender, smoking and hypertension are important factors associated with CAS. Patients with CAS had a significantly higher mRs score after 90 days. Clinical Trial Registration-URL: https://doi.org/10.1186/ISRCTN66140176 Unique identifier: ISRCTN66140176

scholarly journals Prevalence, predictors and outcome of carotid stenosis. A sub study in the Preventive Antibiotics in Stroke Study (PASS)

2020 ◽  
Author(s):  
Twan van Velzen ◽  
Laurien Kuhrij ◽  
Willeke Westendorp ◽  
Diederik van de Beek ◽  
Paul Nederkoorn
Keyword(s):  
Carotid Artery ◽  
Diagnostic Testing ◽  
Phase Iii ◽  
Significant Shift ◽  
Open Label ◽  
Anterior Circulation ◽  
Unique Identifier ◽  
Clinical Trial Registration ◽  
Stroke Study ◽  
Date Estimate

Abstract Background: The prevalence of carotid artery stenosis (CAS) in acute ischaemic stroke (AIS) patients is historically reported at 15-20%, but an up-to-date estimate is lacking. We hypothesise it is lower than historically reported, due to better risk management to date. The study aims to study prevalence, predictors and survival of CAS in AIS patients. Methods: We included patients with AIS from the Preventive Antibiotics in Stroke Study (PASS), a large Dutch randomized, multicentre, open-label phase III trial that included 2538 patients with acute stroke and randomised between standard care or preventive ceftriaxone. Patients with stroke in the anterior circulation that underwent diagnostic testing of the internal carotid artery (ICA) were eligible for this sub study and used in these secondary analyses. Logistic regression analyses were performed to identify predictors for CAS ≥50%. Additionally, an ordinal regression was performed to assess the association between presence of CAS at baseline and functional outcome at three months on the modified Rankin scale (mRS). Results: 1480 patients with AIS were included; 277 had CAS (18.7%; 95%CI:17.7-19.7). Age, hypertension, smoking and male gender were found as best-fit predictors for presence of CAS. Significant shift in mRS score after 90 days for CAS ≥50% towards a higher mRS score with an OR of 1.66 (95% CI 1.30-2.10) was found.Conclusions: Current prevalence of CAS is 18.7%, which is higher than we expected. Gender, smoking and hypertension are important factors associated with CAS. Patients with CAS had a significantly higher mRs score after 90 days. Clinical Trial Registration-URL: https://doi.org/10.1186/ISRCTN66140176 Unique identifier: ISRCTN66140176

scholarly journals Prevalence, predictors and outcome of carotid stenosis: a sub study in the Preventive Antibiotics in Stroke Study (PASS)

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Twan J van Velzen ◽  
Laurien S Kuhrij ◽  
Willeke F Westendorp ◽  
Diederik van de Beek ◽  
Paul J Nederkoorn
Keyword(s):  
Carotid Artery ◽  
Diagnostic Testing ◽  
Phase Iii ◽  
Significant Shift ◽  
Open Label ◽  
Anterior Circulation ◽  
Unique Identifier ◽  
Stroke Study ◽  
Open Label Phase ◽  
Date Estimate

Abstract Background The prevalence of carotid artery stenosis (CAS) in acute ischaemic stroke (AIS) patients is historically reported at 15–20%, but an up-to-date estimate is lacking. We hypothesise it is lower than historically reported, due to better risk management to date. The study aims to study prevalence, predictors and survival of CAS in AIS patients. Methods We included patients with AIS from the Preventive Antibiotics in Stroke Study (PASS), a large Dutch randomized, multicentre, open-label phase III trial that included 2538 patients with acute stroke and randomised between standard care or preventive ceftriaxone. Patients with stroke in the anterior circulation that underwent diagnostic testing of the internal carotid artery (ICA) were eligible for this sub study and used in these secondary analyses. Logistic regression analyses were performed to identify predictors for CAS ≥ 50%. Additionally, an ordinal regression was performed to assess the association between presence of CAS at baseline and functional outcome at three months on the modified Rankin scale (mRS). Results 1480 patients with AIS were included; 277 had CAS (18.7%; 95%CI:17.7-19.7). Age, hypertension, smoking and male gender were found as best-fit predictors for presence of CAS. Significant shift in mRS score after 90 days for CAS ≥50% towards a higher mRS score with an OR of 1.66 (95% CI 1.30-2.10) was found. Conclusions Current prevalence of CAS is 18.7%, which is higher than we expected. Gender, smoking and hypertension are important factors associated with CAS. Patients with CAS had a significantly higher mRs score after 90 days. Trial registration Unique identifier:ISRCTN66140176

scholarly journals A Phase III open-label trial to evaluate efficacy and safety of CPI-613 plus modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) in patients with metastatic adenocarcinoma of the pancreas

2019 ◽  
Vol 15 (28) ◽  
pp. 3189-3196 ◽  
Author(s):  
Philip A Philip ◽  
Marc E Buyse ◽  
Angela T Alistar ◽  
Caio MSPR Lima ◽  
Sanjeev Luther ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Clinical Trial ◽  
Response Rate ◽  
Objective Response ◽  
Phase Iii ◽  
Metastatic Adenocarcinoma ◽  
Open Label ◽  
Clinical Trial Registration ◽  
Entry Points ◽  
Adenocarcinoma Of The Pancreas

Devimistat (CPI-613®) is a novel lipoate analog that inhibits the tricarboxcylic acid cycle at two key carbon entry points. Through its inhibition of pyruvate dehydrogenase and a-ketoglutarate dehydrogenase complexes, devimistat inhibits the entry of glucose and glutamine derived carbons, respectively. Pancreatic cancer is dependent on mitochondrial function for enhanced survival and aggressiveness. In a Phase I study of modified FOLFIRINOX, in combination with devimistat for metastatic pancreatic cancer patients, there was a 61% objective response rate including a 17% complete response rate. This report outlines the rationale and design of the AVENGER 500 study, a Phase III clinical trial of devimistat in combination with modified FOLFIRINOX compared with FOLFIRINOX alone for patients with previously untreated metastatic adenocarcinoma of the pancreas. Clinical trial registration: NCT03504423

scholarly journals Ideal sedation for stroke thrombectomy: a prospective pilot single-center observational study

2019 ◽  
Vol 46 (2) ◽  
pp. E16 ◽  
Author(s):  
M. Asif Taqi ◽  
Sajid S. Suriya ◽  
Ajeet Sodhi ◽  
Syed A. Quadri ◽  
Mudassir Farooqui ◽  
...  
Keyword(s):  
Interventional Radiology ◽  
Ischemic Stroke ◽  
Controlled Trial ◽  
Time Interval ◽  
Open Label ◽  
Anterior Circulation ◽  
Clinical Trial Registration ◽  
Female Ratio ◽  
The Mean ◽  
The Difference

OBJECTIVESeveral retrospective studies have supported the use of conscious sedation (CS) over general anesthesia (GA) as the preferred methods of sedation for stroke thrombectomy, but a recent randomized controlled trial showed no difference in outcomes after CS or GA. The purpose of the Ideal Sedation for Stroke Thrombectomy (ISST) study was to evaluate the difference in time and outcomes in the reperfusion of anterior circulation in ischemic stroke using GA and monitored anesthesia care (MAC).METHODSThe ISST study was a prospective, open-label registry. A total of 40 patients who underwent mechanical thrombectomy for anterior circulation ischemic stroke were enrolled. Informed consent was obtained from each patient before enrollment. The primary endpoint included the interval between the patient’s arrival to the interventional radiology room and reperfusion time. Secondary endpoints were evaluated to estimate the effects on the outcome of patients between the 2 sedation methods.RESULTSOf the 40 patients, 32 received thrombectomy under MAC and 8 patients under GA. The male-to-female ratio was 18:14 in the MAC group and 4:4 in the GA group. The mean time from interventional radiology room arrival to reperfusion in the GA group was 2 times higher than that in the MAC group. Complete reperfusion (TICI grade 3) was achieved in more than 50% of patients in both groups. The mean modified Rankin Scale score at 3 months was < 2 in the MAC group and > 3 in the GA group (p = 0.021).CONCLUSIONSThe findings from the pilot study showed a significantly shorter time interval between IR arrival and reperfusion and better outcomes in patients undergoing reperfusion for ischemic stroke in the anterior circulation using MAC compared with GA.Clinical trial registration no.: NCT03036631 (clinicaltrials.gov)

Infigratinib in patients with advanced cholangiocarcinoma with FGFR2 gene fusions/translocations: the PROOF 301 trial

2020 ◽  
Vol 16 (30) ◽  
pp. 2375-2384 ◽  
Author(s):  
Shalini Makawita ◽  
Ghassan K Abou-Alfa ◽  
Sameek Roychowdhury ◽  
Saeed Sadeghi ◽  
Ivan Borbath ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Standard Of Care ◽  
Phase Iii ◽  
Front Line ◽  
Open Label ◽  
Poor Overall Survival ◽  
Clinical Trial Registration ◽  
Fgfr2 Gene ◽  
Therapy Option ◽  
Line Setting

Cholangiocarcinoma is an aggressive malignancy with poor overall survival. Approximately 15% of intrahepatic cholangiocarcinomas contain FGFR alterations. Infigratinib is an oral FGFR 1–3 kinase inhibitor. Favorable results from a Phase II trial of infigratinib in advanced/metastatic FGFR-altered cholangiocarcinomas has led to its further investigation in the front-line setting. In this article we describe the design, objectives and rationale for PROOF 301, a Phase III multicenter, open label, randomized trial of infigratinib in comparison to standard of care gemcitabine and cisplatin in advanced/metastatic cholangiocarcinoma with FGFR2 translocations. The results of this study have the potential to define a new role for a chemotherapy-free, targeted therapy option in the front-line setting for these patients. Clinical Trial Registration: NCT03773302 (ClincalTrials.gov)

scholarly journals FIGHT-302: first-line pemigatinib vs gemcitabine plus cisplatin for advanced cholangiocarcinoma with FGFR2 rearrangements

2020 ◽  
Vol 16 (30) ◽  
pp. 2385-2399 ◽  
Author(s):  
Tanios S Bekaii-Saab ◽  
Juan W Valle ◽  
Eric Van Cutsem ◽  
Lorenza Rimassa ◽  
Junji Furuse ◽  
...  
Keyword(s):  
Objective Response ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Survival Duration ◽  
Efficacy And Safety ◽  
First Line ◽  
Open Label ◽  
Clinical Trial Registration ◽  
Duration Of Response

FGFR2 rearrangements resulting in dysregulated signaling are drivers of cholangiocarcinoma (CCA) tumorigenesis, and occur almost exclusively in intrahepatic CCA. Pemigatinib, a selective, potent, oral inhibitor of FGFR1–3, has demonstrated efficacy and safety in a Phase II study of patients with previously treated locally advanced/metastatic CCA harboring FGFR2 fusions/rearrangements. We describe the study design of FIGHT-302, an open-label, randomized, active-controlled, multicenter, global, Phase III study comparing the efficacy and safety of first-line pemigatinib versus gemcitabine plus cisplatin in patients with advanced CCA with FGFR2 rearrangements (NCT03656536). The primary end point is progression-free survival; secondary end points are objective response rate, overall survival, duration of response, disease control rate, safety and quality of life. Clinical Trial Registration: NCT03656536 ( ClinicalTrials.gov )

scholarly journals SAFE study (Safety and efficacy Analysis of FRED Embolic device in aneurysm treatment): 1-year clinical and anatomical results

2018 ◽  
Vol 11 (2) ◽  
pp. 184-189 ◽  
Author(s):  
Laurent Pierot ◽  
Laurent Spelle ◽  
Jérôme Berge ◽  
Anne-Christine Januel ◽  
Denis Herbreteau ◽  
...  
Keyword(s):  
Flow Direction ◽  
Clinical Event ◽  
Anterior Communicating Artery ◽  
Anterior Circulation ◽  
Unique Identifier ◽  
Clinical Trial Registration ◽  
Safety And Efficacy ◽  
Mortality And Morbidity ◽  
Efficacy Analysis ◽  
Aneurysm Treatment

Background and purposeFlow diversion is an innovative and increasingly used endovascular treatment for intracranial aneurysms. Its initial evaluation with the first devices available showed good efficacy of this treatment with variable safety results. The Flow Direction Endoluminal Device (FRED) has a specific design and was evaluated in a single-arm, multicenter, prospective, Good Clinical Practice study: SAFE (Safety and efficacy Analysis of FRED Embolic device in aneurysm treatment). This analysis reports clinical results at 1 year and anatomical results at 6 months and 1 year.MethodsPatients with unruptured and recanalized aneurysms located in the anterior circulation treated with FRED and FRED Jr were prospectively included. A Clinical Event Committee and a Core Laboratory independently evaluated clinical outcome and anatomical results.ResultsThirteen interventional neuroradiology centers included 103 patients/aneurysms. Aneurysm locations were supraclinoid internal carotid artery (ICA) in 71 (68.9%), cavernous ICA in 15 (14.6%), anterior cerebral or anterior communicating artery in 9 (8.7%), and middle cerebral artery in 8 (7.8%). Most aneurysms were small (<10 mm) in 71 patients (68.9%). Cumulative 1-year mortality and morbidity rates were 2/103 (1.9%) and 3/103 (2.9%), respectively, one death being related to cancer. At 1 year, anatomical results were: complete occlusion in 66/90 patients (73.3%), neck remnant in 7/90 patients (7.8%), and aneurysm remnant in 17/90 patients (18.9%).ConclusionsSAFE study analysis at 1 year confirms the excellent safety profile of the FRED device for aneurysm treatment, with low morbidity and mortality rates (2.9% and 1.9%, respectively) and demonstrates its efficacy (adequate occlusion in 73/90 (81.1%)).Clinical trial registrationUnique identifier: NCT02921698; Results.

scholarly journals Prospective, Multicenter, Single-Arm Study of Mechanical Thrombectomy Using Solitaire Flow Restoration in Acute Ischemic Stroke

Stroke ◽  
2013 ◽  
Vol 44 (10) ◽  
pp. 2802-2807 ◽  
Author(s):  
Vitor M. Pereira ◽  
Jan Gralla ◽  
Antoni Davalos ◽  
Alain Bonafé ◽  
Carlos Castaño ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Mechanical Thrombectomy ◽  
Hemorrhagic Transformation ◽  
Anterior Circulation ◽  
Unique Identifier ◽  
Vessel Occlusion ◽  
Clinical Trial Registration ◽  
End Point ◽  
Flow Restoration

Background and Purpose— Mechanical thrombectomy using stent retriever devices have been advocated to increase revascularization in intracranial vessel occlusion. We present the results of a large prospective study on the use of the Solitaire Flow Restoration in patients with acute ischemic stroke. Methods— Solitaire Flow Restoration Thrombectomy for Acute Revascularization was an international, multicenter, prospective, single-arm study of Solitaire Flow Restoration thrombectomy in patients with large vessel anterior circulation strokes treated within 8 hours of symptom onset. Strict criteria for site selection were applied. The primary end point was the revascularization rate (thrombolysis in cerebral infarction ≥2b) of the occluded vessel as determined by an independent core laboratory. The secondary end point was the rate of good functional outcome (defined as 90-day modified Rankin scale, 0–2). Results— A total of 202 patients were enrolled across 14 comprehensive stroke centers in Europe, Canada, and Australia. The median age was 72 years, 60% were female patients. The median National Institute of Health Stroke Scale was 17. Most proximal intracranial occlusion was the internal carotid artery in 18%, and the middle cerebral artery in 82%. Successful revascularization was achieved in 79.2% of patients. Device and procedure-related severe adverse events were found in 7.4%. Favorable neurological outcome was found in 57.9%. The mortality rate was 6.9%. Any intracranial hemorrhagic transformation was found in 18.8% of patients, 1.5% were symptomatic. Conclusions— In this single-arm study, treatment with the Solitaire Flow Restoration device in intracranial anterior circulation occlusions results in high rates of revascularization, low risk of clinically relevant procedural complications, and good clinical outcomes in combination with low mortality at 90 days. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01327989.

scholarly journals Efficacy and safety of octanorm (cutaquig®) in adults with primary immunodeficiencies with predominant antibody deficiency: a prospective, open-label study

Immunotherapy ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 299-309
Author(s):  
Elena Latysheva ◽  
Yulia Rodina ◽  
Liudmila Sizyakina ◽  
Areg Totolian ◽  
Irina Tuzankina
Keyword(s):  
Quality Of Life ◽  
Bacterial Infections ◽  
Short Form ◽  
Primary Immunodeficiencies ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Open Label ◽  
Clinical Trial Registration ◽  
Registration Number

Aim: To evaluate efficacy and safety of octanorm (16.5% subcutaneous immunoglobulin) in adult patients with primary immunodeficiencies. Patients & methods: Primary immunodeficiencies patients (18–70 years) previously treated with intravenous immunoglobulin were included in this Phase III study. Octanorm was administered subcutaneously once weekly over 8 months. End points included infections, adverse events and quality of life. Results: 25 patients (mean age 35.2 years, female 60.0%) were recruited, 24 completed the study. Mean dose of octanorm was 0.11 g/kg/week. No serious bacterial infections occurred. Three patients (12.0%) had an adverse event (mild) assessed as related to octanorm. Both the mental and physical summary 36-item Short Form Health Survey scores were improved. Conclusion: Octanorm is effective, safe and improves quality of life. Clinical Trial registration number: NCT03988426.

Endovascular Treatment versus Sonothrombolysis for Acute Ischemic Stroke

2015 ◽  
Vol 40 (5-6) ◽  
pp. 205-214 ◽  
Author(s):  
Matthias Reinhard ◽  
Christian A. Taschner ◽  
Nicole Hörsch ◽  
Arthur Allignol ◽  
Christoph J. Maurer ◽  
...  
Keyword(s):  
Endovascular Treatment ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Functional Independence ◽  
Anterior Circulation ◽  
Unique Identifier ◽  
Clinical Trial Registration ◽  
Systemic Thrombolysis ◽  
Stent Retrieval ◽  
Symptomatic Intracerebral Hemorrhage

Background: Currently, there are 2 strategies to increase the effect of systemic thrombolysis with alteplase (rtPA) in acute major stroke: endovascular treatment via stent retrieval and ultrasound enhancement (sonothrombolysis). This study compares these 2 approaches in patients with proximal intracranial occlusion of the anterior circulation. Methods: Consecutive data on the treatment outcome of acute middle cerebral artery (M1) or carotid T occlusion were collected from 2 stroke centers: one center used rtPA plus endovascular stent retrieval as standard treatment and the other rtPA plus ultrasound (sonothrombolysis). The primary outcome was functional independence (modified Rankin scale (mRS) 0-2) after neurorehabilitation. Results: A total of 132 patients were assessed (n = 73 endovascular, n = 59 sonothrombolysis). The rate of functional independence was higher for endovascular treatment (adjusted OR 3.89 (95% CI 1.36-12.58)). Additionally, ordinal mRS analysis favored the endovascular strategy (adjusted common OR 1.70 (95% CI 0.88-3.31)). Subgroup analysis showed that endovascular treatment was superior for carotid T occlusion (adjusted common OR 5.61 (95% CI 1.60-20.93)), but not for middle cerebral artery occlusion (adjusted common OR 1.07 (95% CI 0.47-2.43)). Symptomatic intracerebral hemorrhage occurred in 3 patients from the endovascular group. Conclusions: This observational study suggests that endovascular treatment of acute major anterior circulation stroke is superior to sonothrombolysis in terms of functional outcome. This benefit seems to pertain primarily to patients with carotid T occlusion, whereas patients with M1 occlusion seem to profit in a similar way from both methods. (Clinical Trial Registration: URL: http://www.germanctr.de. Unique identifier: DRKS0000​5305.)

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