Pentoxifylline in acute nonhemorrhagic stroke. A randomized, placebo-controlled double-blind trial.

Hsu, Chung Y.; Norris, John W.; Hogan, Edward L.; Bladin, Peter F.; Dinsdale, Henry B.; Yatsu, Frank M.; Earnest, Michael P.; Scheinberg, Peritz; Lr, Caplan; Karp, Herbert R.

doi:10.1161/01.str.19.6.716

Cited by 70 publications

(27 citation statements)

References 30 publications

(17 reference statements)

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“…430,431 In one trial, pentoxifylline and propentofylline were administered via continuous intravenous infusion over a 3-day period in patients experiencing an acute ischemic event. 432 Other studies continued infusions for 5 days, as in the trial by Chan and Kay in 1993, or 7 days, as in the trial of Huber et al in 1993. 433,434 Early case fatality, defined as within 4 weeks, was evaluated in several trials of pentoxifylline.…”

Section: B Vasodilators In Acute Ischemic Strokementioning

confidence: 99%

“…433,434 Early case fatality, defined as within 4 weeks, was evaluated in several trials of pentoxifylline. [432][433][434][435] The trial conducted by Chan and Kay found a large reduction in the odds of early death; however, this was not borne out in other studies. Two trials demonstrated a nonsignificant reduction in early death or deterioration.…”

Section: B Vasodilators In Acute Ischemic Strokementioning

confidence: 99%

“…The trial by Hsu et al demonstrated that patients with profound neurological deficit derived the greatest benefit from pentoxifylline. 432 …”

Section: B Vasodilators In Acute Ischemic Strokementioning

confidence: 99%

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Guidelines for the Early Management of Adults With Ischemic Stroke

Adams¹,

Zoppo²,

Alberts³

et al. 2007

Circulation

1,059

745

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Purpose-Our goal is to provide an overview of the current evidence about components of the evaluation and treatment of adults with acute ischemic stroke. The intended audience is physicians and other emergency healthcare providers who treat patients within the first 48 hours after stroke. In addition, information for healthcare policy makers is included. Key Words: AHA Scientific Statements Ⅲ emergency medical services Ⅲ stroke Ⅲ acute cerebral infarction Ⅲ tissue plasminogen activator †Deceased. The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. Methods-Members

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Section: B Vasodilators In Acute Ischemic Strokementioning

confidence: 99%

Section: B Vasodilators In Acute Ischemic Strokementioning

confidence: 99%

See 1 more Smart Citation

Guidelines for the Early Management of Adults With Ischemic Stroke

Adams¹,

Zoppo²,

Alberts³

et al. 2007

Circulation

1,059

745

View full text Add to dashboard Cite

show abstract

“…Followup was 28 days. The groups did not differ in mortality or functional deficit (Hsu et al, 1988).…”

Section: A Miscellany Of Other Agents Studied Without Success In Largmentioning

confidence: 80%

Neuroprotection for ischemic stroke: Past, present and future

2008

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Neuroprotection for ischemic stroke refers to strategies, applied singly or in combination, that antagonize the injurious biochemical and molecular events that eventuate in irreversible ischemic injury. There has been a recent explosion of interest in this field, with over 1000 experimental papers and over 400 clinical articles appearing within the past 6 years. These studies, in turn, are the outgrowth of three decades of investigative work to define the multiple mechanisms and mediators of ischemic brain injury, which constitute potential targets of neuroprotection. Rigorously conducted experimental studies in animal models of brain ischemia provide incontrovertible proof-of-principle that high-grade protection of the ischemic brain is an achievable goal. Nonetheless, many agents have been brought to clinical trial without a sufficiently compelling evidence-based pre-clinical foundation. At this writing, around 160 clinical trials of neuroprotection for ischemic stroke have been initiated. Of the approximately 120 completed trials, two-thirds were smaller early-phase safetyfeasibility studies. The remaining one-third were typically larger (>200 subjects) phase II or III trials, but, disappointingly, only fewer than one-half of these administered neuroprotective therapy within the 4-6 hour therapeutic window within which efficacious neuroprotection is considered to be achievable. This fact alone helps to account for the abundance of "failed" trials.This review presents a close survey of the most extensively evaluated neuroprotective agents and classes and considers both the strengths and weakness of the pre-clinical evidence as well as the results and shortcomings of the clinical trials themselves. Among the agent-classes considered are calcium channel blockers; glutamate antagonists; GABA agonists; antioxidants/radical scavengers; phospholipid precursor; nitric oxide signal-transduction down-regulator; leukocyte inhibitors; hemodilution; and a miscellany of other agents. Among promising ongoing efforts, therapeutic hypothermia, high-dose human albumin therapy, and hyperacute magnesium therapy are considered in detail. The potential of combination therapies is highlighted. Issues of clinical-trial funding, the need for improved translational strategies and clinical-trial design, and "thinking outside the box" are emphasized. Part I: Neuroprotection -from Past to the PresentNeuroprotection for ischemic brain injury has emerged only recently as a topic of serious biomedical inquiry. A MEDLINE survey (PubMed, 2007) reveals virtually no publications on this topic until the early 1990's but a remarkable surge in publications over the past 10 years Correspondence and reprint requests to:

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“…This model accounted for 62% of the observed variation and was based on 11 studies: NIHSS predicted ϭ0.42ϫmaximum ageϪ0. 22 ϫtime window Ϫ20.9…”

Section: Resultsmentioning

confidence: 99%

Entry Criteria and Baseline Characteristics Predict Outcome in Acute Stroke Trials

Uchino

Billheimer

Cramer

2001

Stroke

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Background and Purpose-We sought to study the range of entry criteria and baseline characteristics in acute stroke trials and to understand their effects on patient outcomes. Methods-Randomized, placebo-controlled therapeutic trials in patients with acute ischemic stroke were identified. Entry criteria, baseline clinical characteristics, and outcome were extracted for the placebo group of each trial. The relationship between key variables was then determined. Results-Across 90 placebo groups identified, there was great variation in entry criteria and outcome measures. This was associated with divergent outcomes; for example, in some studies most placebo group patients died, while in other studies nearly all had no disability. Entry criteria were significantly correlated with outcome; for example, higher age cutoff for study entry correlated with 3-month mortality. Entry criteria also predicted baseline clinical characteristics; for example, wider time window for study entry correlated directly with time to treatment and inversely with stroke severity (initial National Institutes of Health Stroke Scale score). Baseline characteristics predicted outcome. Greater stroke severity predicted higher 3-month mortality rate; despite this, successful thrombolytic trials have enrolled more severe strokes than most trials. The mean age of enrollees also predicted 3-month mortality and was inversely related to percentage of patients with 3-month Barthel Index score Ն95. The strongest predictors of 3-month mortality were obtained with multivariate models. Conclusions-Acute stroke studies vary widely in entry criteria and outcome measures. Across multiple studies, differences in entry criteria, and the baseline clinical characteristics they predict, influence patient outcomes along a continuum. In some studies, enrolling a specific subset of patients may have improved the chances of identifying a treatment-related effect, while in others, such chances may have been reduced. These findings may be useful in the design of future stroke therapeutic trials.

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Pentoxifylline in acute nonhemorrhagic stroke. A randomized, placebo-controlled double-blind trial.

Cited by 70 publications

References 30 publications

Guidelines for the Early Management of Adults With Ischemic Stroke

Guidelines for the Early Management of Adults With Ischemic Stroke

Neuroprotection for ischemic stroke: Past, present and future

Entry Criteria and Baseline Characteristics Predict Outcome in Acute Stroke Trials

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