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  • 1
    Online Resource
    Online Resource
    The Middle East–North Africa Region: A Cocoon for Clinical Trials
    Informa UK Limited ; 2015
    In:  Accountability in Research Vol. 22, No. 4 ( 2015-07-04), p. 201-204
    Details
    In: Accountability in Research, Informa UK Limited, Vol. 22, No. 4 ( 2015-07-04), p. 201-204
    Type of Medium: Online Resource
    ISSN: 0898-9621 , 1545-5815
    URL: Article
    DOI: 10.1080/08989621.2015.1015835
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2015
    detail.hit.zdb_id: 2069334-5
    SSG: 5,21
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  • 2
    Online Resource
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    Vascular Occlusion Enables Selecting Acute Ischemic Stroke Patients for Treatment With Desmoteplase
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Stroke Vol. 43, No. 6 ( 2012-06), p. 1561-1566
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 43, No. 6 ( 2012-06), p. 1561-1566
    Abstract: Desmoteplase is a novel and highly fibrin-specific thrombolytic agent. Evidence of safety and efficacy was obtained in 2 phase II trials (Desmoteplase In Acute Ischemic Stroke [DIAS] and Desmoteplase for Acute Ischemic Stroke [DEDAS] ). The DIAS-2 phase III trial did not replicate the positive phase II efficacy findings. Post hoc analyses were performed with the aim of predicting treatment responders based on CTA and MRA. Methods— Patients were grouped according to vessel status (Thrombolysis In Myocardial Infarction [TIMI] grade) for logistic regression of clinical response, applying the data from DIAS-2 as well as the pooled data from DIAS, DEDAS, and DIAS-2. Results— In DIAS-2, a substantial number of mismatch-selected patients (126/179; 70%) presented with a normal flow/low-grade stenosis (TIMI 2–3) at screening, with the majority having a favorable outcome at day 90. In contrast, favorable outcome rates in patients with vessel occlusion/high-grade stenosis (TIMI 0–1) were 18% with placebo versus 36% and 27% with desmoteplase 90 and 125 μg/kg, respectively. The clinical effect based on the pooled data from DIAS, DEDAS, and DIAS-2 was favorable for desmoteplase-treated patients presenting with TIMI 0 to 1 at baseline (OR, 4.144; 95% CI, 1.40–12.23; P =0.010). There was no desmoteplase treatment benefit in patients presenting with TIMI 2 to 3 (OR, 1.109). Conclusions— In this sample of patients with a mismatch diagnosed, proximal vessel occlusion or severe stenosis was associated with clinically beneficial treatment effects of desmoteplase. Selecting patients using CTA or MRA in clinical trials of thrombolytic therapy is justifiable. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov . Unique identifiers: NCT00638781, NCT00638248, NCT00111852.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.111.642322
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 1467823-8
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  • 3
    Online Resource
    Online Resource
    Refinement of the Magnetic Resonance Diffusion-Perfusion Mismatch Concept for Thrombolytic Patient Selection : Insights From the Desmoteplase in Acute Stroke Trials
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Stroke Vol. 43, No. 9 ( 2012-09), p. 2313-2318
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 43, No. 9 ( 2012-09), p. 2313-2318
    Abstract: The DIAS-2 study was the only large, randomized, intravenous, thrombolytic trial that selected patients based on the presence of ischemic penumbra. However, DIAS-2 did not confirm the positive findings of the smaller DEDAS and DIAS trials, which also used penumbral selection. Therefore, a reevaluation of the penumbra selection strategy is warranted. Methods— In post hoc analyses we assessed the relationships of magnetic resonance imaging–measured lesion volumes with clinical measures in DIAS-2, and the relationships of the presence and size of the diffusion-perfusion mismatch with the clinical effect of desmoteplase in DIAS-2 and in pooled data from DIAS, DEDAS, and DIAS-2. Results— In DIAS-2, lesion volumes correlated with National Institutes of Health Stroke Scale (NIHSS) at both baseline and final time points ( P 〈 0.0001), and lesion growth was inversely related to good clinical outcome ( P =0.004). In the pooled analysis, desmoteplase was associated with 47% clinical response rate (n=143) vs 34% in placebo (n=73; P =0.08). For both the pooled sample and for DIAS-2, increasing the minimum baseline mismatch volume (MMV) for inclusion increased the desmoteplase effect size. The odds ratio for good clinical response between desmoteplase and placebo treatment was 2.83 (95% confidence interval, 1.16–6.94; P =0.023) for MMV 〉 60 mL. Increasing the minimum NIHSS score for inclusion did not affect treatment effect size. Conclusions— Pooled across all desmoteplase trials, desmoteplase appears beneficial in patients with large MMV and ineffective in patients with small MMV. These results support a modified diffusion-perfusion mismatch hypothesis for patient selection in later time-window thrombolytic trials. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique Identifiers: NCT00638781, NCT00638248, NCT00111852.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/STROKEAHA.111.642348
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
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  • 4
    Online Resource
    Online Resource
    The Desmoteplase in Acute Ischemic Stroke Trial (DIAS) : A Phase II MRI-Based 9-Hour Window Acute Stroke Thrombolysis Trial With Intravenous Desmoteplase
    Ovid Technologies (Wolters Kluwer Health) ; 2005
    In:  Stroke Vol. 36, No. 1 ( 2005-01), p. 66-73
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 36, No. 1 ( 2005-01), p. 66-73
    Abstract: Background and Purpose— Most acute ischemic stroke patients arrive after the 3-hour time window for recombinant tissue plasminogen activator (rtPA) administration. The Desmoteplase In Acute Ischemic Stroke trial (DIAS) was a dose-finding randomized trial designed to evaluate the safety and efficacy of intravenous desmoteplase, a highly fibrin-specific and nonneurotoxic thrombolytic agent, administered within 3 to 9 hours of ischemic stroke onset in patients with perfusion/diffusion mismatch on MRI. Methods— DIAS was a placebo-controlled, double-blind, randomized, dose-finding phase II trial. Patients with National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch were eligible. Of 104 patients, the first 47 (referred to as Part 1) were randomized to fixed doses of desmoteplase (25 mg, 37.5 mg, or 50 mg) or placebo. Because of an excessive rate of symptomatic intracranial hemorrhage (sICH), lower weight-adjusted doses escalating through 62.5 μg/kg, 90 μg/kg, and 125 μg/kg were subsequently investigated in 57 patients (referred to as Part 2). The safety endpoint was the rate of sICH. Efficacy endpoints were the rate of reperfusion on MRI after 4 to 8 hours and clinical outcome as assessed by NIHSS, modified Rankin scale, and Barthel Index at 90 days. Results— Part 1 was terminated prematurely because of high rates of sICH with desmoteplase (26.7%). In Part 2, the sICH rate was 2.2%. No sICH occurred with placebo in either part. Reperfusion rates up to 71.4% ( P =0.0012) were observed with desmoteplase (125 μg/kg) compared with 19.2% with placebo. Favorable 90-day clinical outcome was found in 22.2% of placebo-treated patients and between 13.3% (62.5 μg/kg; P =0.757) and 60.0% (125 μg/kg; P =0.0090) of desmoteplase-treated patients. Early reperfusion correlated favorably with clinical outcome ( P =0.0028). Favorable outcome occurred in 52.5% of patients experiencing reperfusion versus 24.6% of patients without reperfusion. Conclusions— Intravenous desmoteplase administered 3 to 9 hours after acute ischemic stroke in patients selected with perfusion/diffusion mismatch is associated with a higher rate of reperfusion and better clinical outcome compared with placebo. The sICH rate with desmoteplase was low, using doses up to 125 μg/kg.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/01.STR.0000149938.08731.2c
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2005
    detail.hit.zdb_id: 1467823-8
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  • 5
    Online Resource
    Online Resource
    Dose Escalation of Desmoteplase for Acute Ischemic Stroke (DEDAS) : Evidence of Safety and Efficacy 3 to 9 Hours After Stroke Onset
    Ovid Technologies (Wolters Kluwer Health) ; 2006
    In:  Stroke Vol. 37, No. 5 ( 2006-05), p. 1227-1231
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 37, No. 5 ( 2006-05), p. 1227-1231
    Abstract: Background and Purpose— Desmoteplase is a novel plasminogen activator with favorable features in vitro compared with available agents. This study evaluated safety and efficacy of intravenous (IV) desmoteplase in patients with perfusion/diffusion mismatch on MRI 3 to 9 hours after onset of acute ischemic stroke. Methods— DEDAS was a placebo-controlled, double-blind, randomized, dose-escalation study investigating doses of 90 μg/kg and 125 μg/kg desmoteplase. Eligibility criteria included baseline National Institute of Health Stroke Scale (NIHSS) scores of 4 to 20 and MRI evidence of perfusion/diffusion mismatch. The safety end point was the rate of symptomatic intracranial hemorrhage. Primary efficacy co-end points were MRI reperfusion 4 to 8 hours after treatment and good clinical outcome at 90 days. The primary analyses were intent-to-treat. Before unblinding, a target population, excluding patients violating specific MRI criteria, was defined. Results— Thirty-seven patients were randomized and received treatment (intent-to-treat; placebo: n=8; 90 μg/kg: n=14; 125 μg/kg: n=15). No symptomatic intracranial hemorrhage occurred. Reperfusion was achieved in 37.5% (95% CI [8.5; 75.5]) of placebo patients, 18.2% (2.3; 51.8) of patients treated with 90 μg/kg desmoteplase, and 53.3% (26.6; 78.7) of patients treated with 125 μg/kg desmoteplase. Good clinical outcome at 90 days occurred in 25.0% (3.2; 65.1) treated with placebo, 28.6% (8.4; 58.1) treated with 90 μg/kg desmoteplase and 60.0% (32.3; 83.7) treated with 125 μg/kg desmoteplase. In the target population (n=25), the difference compared with placebo increased and was statistically significant for good clinical outcome with 125 μg/kg desmoteplase ( P =0.022). Conclusions— Treatment with IV desmoteplase 3 to 9 hours after ischemic stroke onset appears safe. At a dose of 125 μg/kg desmoteplase appeared to improve clinical outcome, especially in patients fulfilling all MRI criteria. The results of DEDAS generally support the results of its predecessor study, Desmoteplase in Acute Ischemic Stroke (DIAS).
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/01.STR.0000217403.66996.6d
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2006
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  • 6
    Online Resource
    Online Resource
    Recognising, understanding and managing high conflict behaviours in healthcare
    Oxford University Press (OUP) ; 2021
    In:  Postgraduate Medical Journal Vol. 97, No. 1144 ( 2021-02-01), p. 123-124
    Details
    In: Postgraduate Medical Journal, Oxford University Press (OUP), Vol. 97, No. 1144 ( 2021-02-01), p. 123-124
    Type of Medium: Online Resource
    ISSN: 1469-0756 , 0032-5473
    URL: Article
    DOI: 10.1136/postgradmedj-2020-139173
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 2009568-5
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  • 7
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    Online Resource
    When Tithonus met corona: the COVID-19 pandemic and acute illness in the elderly
    BMJ ; 2020
    In:  BMJ Supportive & Palliative Care Vol. 10, No. 4 ( 2020-12), p. 372-373
    Details
    In: BMJ Supportive & Palliative Care, BMJ, Vol. 10, No. 4 ( 2020-12), p. 372-373
    Type of Medium: Online Resource
    ISSN: 2045-435X , 2045-4368
    URL: Article
    DOI: 10.1136/bmjspcare-2020-002424
    Language: English
    Publisher: BMJ
    Publication Date: 2020
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  • 8
    Online Resource
    Online Resource
    Intravenous desmoteplase in patients with acute ischaemic stroke selected by MRI perfusion–diffusion weighted imaging or perfusion CT (DIAS-2): a prospective, randomised, double-blind, placebo-controlled study
    Elsevier BV ; 2009
    In:  The Lancet Neurology Vol. 8, No. 2 ( 2009-02), p. 141-150
    Details
    In: The Lancet Neurology, Elsevier BV, Vol. 8, No. 2 ( 2009-02), p. 141-150
    Type of Medium: Online Resource
    ISSN: 1474-4422
    URL: Article
    DOI: 10.1016/S1474-4422(08)70267-9
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2009
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  • 9
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    Online Resource
    Abstract 2600: Refinement of the MR Diffusion-perfusion Mismatch Concept for Thrombolytic Patient Selection: Insights from the Desmoteplase In Acute Stroke Trials
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Stroke Vol. 43, No. suppl_1 ( 2012-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 43, No. suppl_1 ( 2012-02)
    Abstract: The DIAS-2 study was the only large, randomized intravenous thrombolytic trial that selected patients based on the presence of ischemic penumbra. However, DIAS-2 did not confirm the positive findings of the smaller DEDAS and DIAS trials, which also used penumbral selection. Therefore a reevaluation of the penumbra selection strategy is warranted. In post-hoc analyses we assessed the relationships of MRI-measured lesion volumes to clinical measures in DIAS-2, and the relationships of the presence and size of the diffusion-perfusion mismatch to the clinical effect of desmoteplase in DIAS-2 (MRI-selected patients) and in pooled data from MRI-selected 90- and 125-μg/kg dose groups in DIAS, DEDAS, and DIAS-2. In DIAS-2, lesion volumes correlated with NIHSS at both baseline and final time points (P 〈 0·0001), and lesion growth was inversely related to good clinical outcome (P=0.004). In the pooled analysis, treatment was associated with 47% clinical response rate in desmoteplase (n=143) versus 34% in placebo (n=73; P=0.08). For both the pooled sample and for DIAS-2, increasing the minimum baseline mismatch volume (MMV) for inclusion increased the desmoteplase effect size, preferentially decreasing the placebo-response rate. There was a trend of statistically significant differences in effect size in ≤60 mL versus 〉 60 mL baseline mismatch subgroups (P=0.083). The odds ratio for good clinical response between desmoteplase and placebo treatment was 2.83 (95% CI, 1.16-6.94, P=0.023) for a MMV 〉 60 mL. Increasing the minimum NIHSS for inclusion did not affect treatment effect size. Pooled across all desmoteplase trials, penumbral selection by MRI diffusion-perfusion mismatch favored desmoteplase clinical benefit, especially for larger MMV. Based on these results, a three-fold reduction in future trial sample size requirements would be achieved using a criterion of baseline MMV 〉 60 mL over any visible mismatch. These results support a modified diffusion-perfusion mismatch hypothesis for patient selection in later-time-window thrombolytic trials.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.43.suppl_1.A2600
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 1467823-8
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  • 10
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    Online Resource
    Abstract 2595: Vascular Occlusion as an Imaging Biomarker for Selecting Acute Ischemic Stroke Patients for Treatment with Desmoteplase
    Ovid Technologies (Wolters Kluwer Health) ; 2012
    In:  Stroke Vol. 43, No. suppl_1 ( 2012-02)
    Details
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 43, No. suppl_1 ( 2012-02)
    Abstract: Desmoteplase is a novel, highly fibrin-specific and non-neurotoxic thrombolytic agent. Evidence of safety and efficacy was obtained in two phase II trials (DIAS and DEDAS). The DIAS-2 phase III trial did not replicate the positive phase II efficacy findings. Post-hoc analyses were performed with the aim of predicting treatment responders based on CT and MR angiography. The predictive value of infarct volume and TIMI grade at baseline with respect to drug response measured by clinical outcome at Day 90 was investigated using DIAS-2 data. Patients were grouped according to vessel status (TIMI grade) for logistic regression of clinical response, applying the data from DIAS-2 as well as the pooled data from DIAS, DEDAS, and DIAS-2. In DIAS-2, a substantial number of mismatch-selected patients (126/179, 70%) presented with a normal flow/low-grade stenosis (TIMI 2-3) at screening, the majority having a favorable outcome at Day 90. In contrast, favorable outcome rates in patients with vessel occlusion/high-grade stenosis (TIMI 0-1) were 18% with placebo versus 36% and 27% with desmoteplase 90 and 125 μg/kg, respectively. The clinical effect size based on the pooled data from DIAS, DEDAS, and DIAS-2 was borderline statistically significantly different (P=0.05) in the TIMI 0-1 and TIMI 2-3 subgroups. It was favorable for desmoteplase-treated patients presenting with TIMI 0-1 at baseline (odds ratio, 4.144; 95% CI, 1.40-12.23; P=0.010), while there was no desmoteplase treatment benefit in patients presenting with TIMI 2-3 (odds ratio, 1.109). In this sample of patients diagnosed with a mismatch, proximal vessel occlusion or severe stenosis was associated with clinically beneficial treatment effects of desmoteplase. Selecting patients using CT or MR angiography in clinical trials of thrombolytic therapy is justifiable.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    URL: Article
    DOI: 10.1161/str.43.suppl_1.A2595
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2012
    detail.hit.zdb_id: 1467823-8
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