Key design elements of successful acute ischemic stroke treatment trials

Yperzeele, L.; Shoamanesh, A.; Venugopalan, Y. V.; Chapman, S.; Mazya, M. V.; Charalambous, M.; Caso, V.; Hacke, W.; Bath, P. M.; Koltsov, I.

Abstract

Purpose: We review key design elements of positive randomized controlled trials (RCTs) in acute ischemic stroke (AIS) treatment and summarize their main characteristics. Method: We searched Medline, Pubmed and Cochrane databases for positive RCTs in AIS treatment. Trials were included if (1) they had a randomized controlled design, with (at least partial) blinding for endpoints, (2) they tested against placebo (or on top of standard therapy in a superiority design) or against approved therapy; (3) the protocol was registered and/or published before trial termination and unblinding (if required at study commencement); (4) the primary endpoint was positive in the intention to treat analysis; and (5) the study findings led to approval of the investigational product and/or high ranked recommendations. A topical approach was used, therefore the findings were summarized as a narrative review. Findings: Seventeen positive RCTs met the inclusion criteria. The majority of trials included less than 1000 patients (n = 15), had highly selective inclusion criteria (n = 16), used the modified Rankin score as a primary endpoint (n = 15) and had a frequentist design (n = 16). Trials tended to be national (n = 12), investigator-initiated and performed with public funding (n = 11). Discussion: Smaller but selective trials are useful to identify efficacy in a particular subgroup of stroke patients. It may also be of advantage to limit the number of participating countries and centers to avoid heterogeneity in stroke management and bureaucratic burden. Conclusion: The key characteristics of positive RCTs in AIS treatment described here may assist in the design of further trials investigating a single intervention with a potentially high effect size.

Citation

Yperzeele, L., Shoamanesh, A., Venugopalan, Y. V., Chapman, S., Mazya, M. V., Charalambous, M., Caso, V., Hacke, W., Bath, P. M., & Koltsov, I. (2023). Key design elements of successful acute ischemic stroke treatment trials. Neurological Research and Practice, 5(1), Article 1. https://doi.org/10.1186/s42466-022-00221-9

• Journal Article Type: Article
• Acceptance Date: Oct 17, 2022
• Online Publication Date: Jan 5, 2023
• Publication Date: Jan 5, 2023
• Deposit Date: Nov 4, 2022
• Publicly Available Date: Jan 5, 2023
• Journal: Neurological Research and Practice
• Electronic ISSN: 2524-3489
• Publisher: BioMed Central
• Peer Reviewed: Peer Reviewed
• Volume: 5
• Issue: 1
• Article Number: 1
• DOI: https://doi.org/10.1186/s42466-022-00221-9
• Public URL: https://nottingham-repository.worktribe.com/output/13179941
• Publisher URL: https://neurolrespract.biomedcentral.com/articles/10.1186/s42466-022-00221-9