Clinical Trials For Cytoprotection In Stroke

AUTOR(ES)

Labiche, Lise A.

FONTE

The American Society for Experimental NeuroTherapeutics

RESUMO

Summary: To date, many cytoprotective drugs have reached the stage of pivotal phase 3 efficacy trials in acute stroke patients. (Table 1) Unfortunately, throughout the neuroprotective literature, the phrase “failure to demonstrate efficacy” prevails as a common thread among the many neutral or negative trials, despite the largely encouraging results encountered in preclinical studies. The reasons for this discrepancy are multiple, and have been discussed by Dr. Zivin in his review. Many of the recent trials have addressed deficiencies of the previous ones with more rigorous trial design, including more specific patient selection criteria (ensure homogeneity of stroke location and severity), stratified randomization algorithms (time-to-treat), narrowed therapeutic time-window and pharmacokinetic monitoring. Current trials have also incorporated biologic surrogate markers of toxicity and outcome such as drug levels and neuroimaging. Lastly, multi-modal therapies and coupled cytoprotection/reperfusion strategies are being investigated to optimize tissue salvage. This review will focus on individual therapeutic strategies and we will emphasize what we have learned from these trials both in terms of trial design and the biologic effect (or lack thereof) of these agents.

Documentos Relacionados

• BOOK REVIEWS: Stroke: Populations, Cohorts, and Clinical Trials.
• Update on intravenous tissue plasminogen activator for acute stroke: from clinical trials to clinical practice
• The experiences of an acute stroke unit--implications for multicentre acute stroke trials.
• Funding Evidence: The National Institute of Neurological Disorders and Stroke Clinical Trials Program
• MRC Guidelines for Good Clinical Practice in Clinical Trials