摘要:

The conducting of effective clinical trials in acute stroke is beset with a range of problems. The entire community involved in such trials (both investigators and sponsors) must attempt to develop high quality protocols; to be responsible for the selection of credible trial centres and to ensure that members of the trial committee are appropriately chosen. The question of who initiates the trial (trialist or sponsor); who collects and analyses the data and the creation of a suitable structure of reimbursement must be addressed. Local Ethics Committees are not suitably equipped for this task which must become the responsibility of a larger, international body.

ISSN:1015-9770    

DOI:10.1159/000107899

出版商:S. Karger AG    

年代:1995

数据来源: Karger

ISSN:1015-9770    

DOI:10.1159/000107808

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

To obtain useful results from clinical trials requires attention to various aspects of the trial design. Important among these is the selection of appropriate endpoints or outcome events. Currently measured endpoints involve determination of impairment, disability or handicap, but these represent three distinct levels of outcome. The importance of psychosocial factors such as social support is being increasingly appreciated as a factor contributing to stroke recovery. In addition, attempts are currently being made to provide suitable measures of the patient''s quality of life. There is a considerable lack of clarity and consistency about the meaning and measurement of this variable. Details are given of a new attempt to produce a reliable scoring system to measure quality of life using the patient''s own ranking of important items. Intermediate (surrogate) endpoints can be of value but only if they are also clinically relevant. Finally, the question of sample size is important for the design of clinical trials. Many published trials have contained too few patients to exclude the possibility of some undetected therapeutic benefit. Stroke trials of the future would seek to combine a range of endpoints, including biochemistry and clinical observation with assessment of life quality based on the reports of patients themselves.

ISSN:1015-9770    

DOI:10.1159/000107900

出版商:S. Karger AG    

年代:1995

数据来源: Karger

ISSN:1015-9770    

DOI:10.1159/000107810

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The development of transoesophageal echocardiography as a relatively non-invasive means of imaging the aortic arch has led to the discovery of this region as a potential cause of stroke. There is in vivo and autopsy evidence that aortic arch atheroma is an independent risk factor for ischaemic stroke and that the risk is of the same order of magnitude as the well established risk factors such as hypertension, carotid stenosis and atrial fibrillation. The most common mechanism of stroke development is probably by virtue of embolic debris lodging within the cerebral circulation. Transoesophageal echocardiography as a means of detecting aortic arch atheroma is indicated in patients with embolic stroke in whom no obvious source of embolism from large arteries or heart can be found. While there is no consensus on how best to manage patients with aortic arch atheroma in a primary or secondary prevention setting, antiplatelet therapy, anticoagulants, thrombolytic agents and surgery have been suggested or used. Further improvements in non-invasive imaging of the aortic arch are likely to lead to a better understanding of its place in the genesis of ischaemic stroke and pave the way for trials of therapy.

ISSN:1015-9770    

DOI:10.1159/000107811

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Trial methodology for clinical trials in stroke depends upon the specific purposes of the particular trial. Phase II clinical investigation is intended to include early controlled clinical trials designed to demonstrate safety, to gather information on the pharmacokinetic profile of the investigational drug and to establish first proof of efficacy. Phase III clinical trials are expanded controlled trails. They are performed after efficacy has been established, at least to a certain degree, and are intended to gather additional evidence on efficacy, plus further evidence of safety and tolerance.

ISSN:1015-9770    

DOI:10.1159/000107901

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The newly developed method of simultaneous bilateral transcranial Doppler sonography (sbTCD) provides a reliable tool for the assessment of hemispheric differences in changes of cerebral blood flow velocities evoked by cognition. Lateralized increase of flow velocity in the middle cerebral arteries (MCA) could be detected in response to specific tasks predominantly processed in either the left or the right hemisphere in all 57 subjects tested. During language processing 83% of right-handers exhibited a significantly higher increase in left-hemispheric blood flow velocity (x = 4.5 ± 2.7%). Among left-handers this was observed in only 57%. A bilateral increase in flow velocity with no significant side differences was found with calculation. Moreover, flow velocity increments in the MCA exceeded those in the anterior cerebral artery (ACA) indicating that the cortical areas most important for arithmetics are supplied by the MCA. Thus, sbTCD is a promising method for the assessment of hemispheric lateralization of higher cortical functions as well as for the localization of active brain areas supplied by the MCA or ACA. In comparison to other methods, the measurement of hemodynamic parameters by sbTCD has the advantage of better time resolution in the range of seconds and of noninvasiveness which allows intrasubject averaging and longitudinal studies

ISSN:1015-9770    

DOI:10.1159/000107812

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

There are intensive international efforts to test promising interventional therapies for ischaemic stroke. National differences in accrual, management and consent could impact on international stroke trials. Information was sought from stroke investigators in 20 countries concerning stroke rates and hospitalization, trial centres, arrival times and triage, neurological involvement and stroke units, consent protocols and use of unproven stroke therapies. Except in developing nations, most patients are hospitalized. Neurologists rarely care for stroke patients and there are few stroke units, despite their proven value. Delays in hospital arrival and triage are common. However, in some countries, most patients arrive within acute trial time windows. Surrogate trial consent is generally accepted, but is under threat and will reduce accrual of patients with aphasia and depressed conscious state. Prevalent unproven acute therapies include heparin, aspirin and glycerol. Stroke trials networks could increase accrual and coordination of acute therapy trials.

ISSN:1015-9770    

DOI:10.1159/000107902

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

This study investigated the effect of 50 mg atenolol in reducing the risk of death, stroke and myocardial infarction after stroke and transient ischaemic attacks (TIA). The study was designed as a Swedish multicentre, randomised, double-blind, parallel group study with randomisation stratified according to age and prognostic score. Seven hundred and twenty patients aged over 40 years who had no contraindications to beta-blockers were included within 3 weeks of a stroke or TIA, with 372 patients (mean age 70.7 years) randomised to the treatment and 348 patients (mean age 70.1 years) to the placebo group. Major strokes made up the index events in 81% of patients in the treatment and 79% of those in the placebo group. The two groups were similar in respect to baseline characteristics. The index event was classified as an ischaemic stroke in 86.8 and 86.3% of patients in the treatment and placebo groups, respectively. Side effects of atenolol and placebo caused 17 and 10% of patients to withdraw from allocated treatment. During the follow-up period (mean 28 months) 51 patients in the treatment group died compared to 60 in the placebo group [relative risk with 95% confidence interval 0.79 (0.54–1.16)] and 74 patients in the treatment group suffered a further major stroke compared to 69 in the placebo group. Twenty-six and 29 patients, respectively, suffered an acute myocardial infarction. Calculations using survival techniques and Cox''s proportional hazard model indicated a reduced risk of death (21%) and myocardial infarction (7%) in the treatment group with no reduction in the risk of further stroke. None of these reductions was statistically significant. Thus the study failed to confirm a statistically significant reduction in death, stroke or myocardial infarction after major stroke or TIA by 50 mg atenolol. However, the results do not exclude a possible secondary prophylactic effect of atenolol in secondary prophylaxis after stroke and TI

ISSN:1015-9770    

DOI:10.1159/000107813

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Collaboration between clinical trial investigators and their sponsors must pay attention to certain guidelines if clinical standards are to be maintained and the interests of the patient safeguarded. At issue are questions of remuneration, record-keeping and competence as well as outcome measures and post-hoc trial analysis. It is suggested that remuneration for clinical trial involvement should not be set at such a high level that other aspects of patient care may be jeopardized. Trials should be conducted in recognised centres involving experienced trialists with the accuracy of patient records monitored by random audits. The design, data collection and analysis should be the responsibility of a Steering Committee which represents all trial participants. The primary outcome measures in acute stroke trials should assess degree of disability or handicap and surrogate end-points should be treated with caution. The use of sub-group analysis should be limited and any such sub-groups should be defined before the trial commences.

ISSN:1015-9770    

DOI:10.1159/000107903

出版商:S. Karger AG    

年代:1995

数据来源: Karger