Design and baseline results of the monosialoganglioside early stroke trial. The EST Study Group.

Rocca, Walter A.; Dorsey, Frank C.; Grigoletto, Francesco; Gent, Michael; Walker, Michael D.; Easton, J. Donald; Bruno, Roberto; Carolei, Antonio; Sancesario, Giuseppe

doi:10.1161/01.str.23.4.519

Cited by 23 publications

(4 citation statements)

References 19 publications

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“…9 We report here the results of a randomized, placebocontrolled, double-blind, multicenter study conducted to assess the efficacy and safety of GM-1 with a loading dose administered within 5 hours after the onset of an ischemic stroke of the cerebral hemispheres: the Early Stroke Trial (EST). The design, organization, and baseline results of the trial were described in detail elsewhere 10 and are only summarized here.…”

Section: Efficacy and Safety Results Of The Early Stroke Trialmentioning

confidence: 99%

Early treatment of stroke with monosialoganglioside GM-1. Efficacy and safety results of the Early Stroke Trial.

Lenzi

Grigoletto

Gent

et al. 1994

Stroke

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The Early Stroke Trial (EST) is a randomized, double-blind, placebo-controlled trial to assess the effect of monosialoganglioside GM-1 in improving recovery in patients who experienced an ischemic supratentorial stroke. Sixteen clinical centers recruited 805 patients, of whom 792 were confirmed to be eligible. Treatment, consisting of a first dose of either 200 mg GM-1 or placebo, was initiated within 5 hours of the onset of stroke; a second dose of either 100 mg GM-1 or placebo was administered 12 hours later. Thereafter, patients received a daily injection of 100 mg GM-1 or placebo intravenously from day 2 through 10 and intramuscularly from day 11 through 21. Patients were followed up for a total of 4 months. Survival was similar in the two treatment groups. Improvement in neurological status, as measured by the change in Canadian Neurological Scale score between baseline and 4-month assessments, was greater in the group receiving GM-1; the observed difference between treatment groups was 0.22 (P = .06). A post hoc analysis in the subgroup of patients treated within 4 hours showed a statistically significant difference, with Canadian Neurological Scale mean improvement of 0.41 (P = .016). GM-1 use was not associated with differences in frequency, nature, or severity of adverse experiences. These findings suggest that GM-1 is safe in the dose and treatment schedule used and that its efficacy in ischemic stroke is greater when given soon after onset of stroke.

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Section: Efficacy and Safety Results Of The Early Stroke Trialmentioning

confidence: 99%

Early treatment of stroke with monosialoganglioside GM-1. Efficacy and safety results of the Early Stroke Trial.

Lenzi

Grigoletto

Gent

et al. 1994

Stroke

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“…with nimodipine. Safety and efficacy trials for neuroprotectants are summarized in table 3 [15, 18, 27, 28, 29, 36, 62, 63, 64, 65, 66]. …”

Section: The Place Of Neuroprotectants In Acute Stroke Managementmentioning

confidence: 99%

Neuroprotection as Initial Therapy in Acute Stroke

1998

Cerebrovasc Dis

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Although a considerable body of scientific data is now available on neuroprotection in acute ischaemic stroke, this field is not yet established in clinical practice. At its third meeting, the European Ad Hoc Consensus Group considered the potential for neuroprotection in acute stroke and the practical problems attendant on the existence of a very limited therapeutic window before irreversible brain damage occurs, and came to the following conclusions. Neuroprotectants in Clinical Development: Convincing clinical evidence for an efficacious neuroprotective treatment in acute stroke is still required. Caution should be exercised in interpreting and extrapolating experimental results to stroke patients, who are a very heterogeneous group. The limitations of the time windows and the outcome measures chosen in trials of acute stroke therapy have an important influence on the results. The overall distribution of functional outcomes provides more statistical information than the proportion above a threshold outcome value. Neurological outcome should also be assessed. Neuroprotectants should not be tested clinically in phase II or phase III trials in a time window that exceeds those determined in experimental studies. The harmful effects of a drug in humans may override its neuroprotective potential determined in animals. Agents that act at several different levels in the ischaemic cascade may be more effective than those with a single mechanism of action. Current In-Hospital Management of Acute Stroke: The four major physiological variables that must be monitored and managed are blood pressure, arterial blood gas levels, body temperature, and glycaemia. The effects of controlling these physiological variables have not been studied in prospective trials, though they may all contribute to the outcome of acute ischaemic stroke and affect the duration of the therapeutic window. Optimal physiological parameters are inherently neuroprotective. Trials of new agents for the treatment of acute stroke should aim to maintain these physiological variables as close to normal as possible, and certainly within strictly defined limits. The Place of Neuroprotectants in Acute Stroke Management: Stroke patients are a very heterogeneous group with respect to stroke mechanisms and severity, general condition, age and co-morbidities. At the present time, the only firm guideline than can be proposed for patient selection is the need for early admission to enable neuroprotectant and/or thrombolytic treatment to be started as soon as possible within the therapeutic window. The severity of potential side-effects will largely determine who should assess a patient with suspected stroke and initiate treatment. There is little information on which to base the duration of neuroprotectant therapy, and more experimental data are needed. Even if prehospital treatment proves to be feasible, it should not replace comprehensive stroke management in a specialist hospital unit. Clinical trials of neuroprotectants should only be performed in stroke units. T...

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“…Another related strategy is to use drugs that target sodium channels whose activation may result in both glutamate release and release of sequestered intracellular calcium [ 191. Gangliosides have also been studied, which may act by blocking translocation of protein kinase C. Recently, clinical trials of gangliosides have been carried out [20].…”

Section: Progress In Neuronal-protective Therapy Researchmentioning

confidence: 99%

Why do all drugs work in animals but none in stroke patients? 2 Neuroprotective therapy

Grotta¹

1995

Journal of Internal Medicine

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Design and baseline results of the monosialoganglioside early stroke trial. The EST Study Group.

Cited by 23 publications

References 19 publications

Early treatment of stroke with monosialoganglioside GM-1. Efficacy and safety results of the Early Stroke Trial.

Early treatment of stroke with monosialoganglioside GM-1. Efficacy and safety results of the Early Stroke Trial.

Neuroprotection as Initial Therapy in Acute Stroke

Why do all drugs work in animals but none in stroke patients? 2 Neuroprotective therapy

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