A Systematic Review and Meta-Analysis of the Efficacy of Piracetam and Piracetam-Like Compounds in Experimental Stroke

Abstract

Background/Objective: Piracetam was a candidate neuroprotective drug for acute stroke ineffective in clinical trial. Here we use systematic review and meta-analysis to describe the evidence supporting a protective effect of piracetam and its derivatives in animal models of stroke. Methods: We present a systematic review of reports describing the use of piracetam and its derivatives in animal models of focal ischaemia, where the outcome was measured as an infarct size or neurological score (Der Simonian and Laird random effects meta-analysis). Results: Only 2 studies, published 10 years after the first clinical trial of piracetam had been initiated, described its efficacy in animal models of stroke. A further 4 studies described the efficacy of related compounds. Piracetam and its derivatives improved the outcome by 30.2% (95% CI = 16.1–44.4). The median study quality was 4/10 (inter-quartile range = 4–6). Conclusion: Piracetam and its derivatives demonstrate neuroprotective efficacy in experimental stroke, but our findings raise concerns about the amount of available data, the quality of the studies and publication bias.

Late, never or non‐existent: the inaccessibility of preclinical evidence for new drugs

“…For instance, FDA guidelines state that ‘summary reports … without individual study results … usually suffices [for an IND application] … lack of … potential effectiveness information should not generally be a reason for a Phase 1 IND to be placed on clinical hold’ (FDA, , p. 11). We are aware of several instances where drugs seem to have been advanced into trials before animal efficacy studies were performed (Horn et al ., ; O'Collins et al ., ; Wheble et al ., ).…”

“…potential effectiveness information should not generally be a reason for a Phase 1 IND to be placed on clinical hold' (FDA, 1995, p. 11). We are aware of several instances where drugs seem to have been advanced into trials before animal efficacy studies were performed (Horn et al, 2001;O'Collins et al, 2006;Wheble et al, 2008).…”

Empirical Evidence of Bias in the Design of Experimental Stroke Studies

“…26 Two studies unpublished at the time of the search were provided by 1 of the authors (27 and Sena and Macleod, unpublished data, 2007); this gave a total of 13 meta-analyses that described outcome in 15 635 animals (the Table).…”

In Vivo Neuroprotective Effects of Alpinetin Against Experimental Ischemic Stroke Damage Through Antioxidant and Anti-Inflammatory Mechanisms

“…While its neuroprotective mechanism(s) are yet to be definitively elucidated, it is hypothesized that piracetam interacts with the polar head groups of phospholipids in the cell membrane, thereby improving membrane fluidity. This enhancement may support essential membrane-associated functions, such as ATP synthesis, ultimately contributing to the preservation of neuronal viability [ 51 ]. Earlier research has indicated that administering piracetam intraperitoneally at doses of 250 or 500 mg/kg body weight at 6, 9, and 22 h following the onset of cerebral artery occlusion can significantly reduce infarct volume in ischemic brain tissue [ 52 ].…”