RIC represents an ideal candidate to enter a multicentre pRCT with a rigorous study design, 10 since previous results from single laboratories support its efficacy, but current phase II–III clinical trials provided inconclusive results.
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9 This paradigm was chosen by the ISO Basic Science steering committee to enter a phase III multicentre pRCT to provide a strong statistical, analytical and reporting power, ultimately predicting drug efficacy before translation to clinic. 7 8 Previous exploratory, single-centre studies have reported efficacy of RIC in reducing the consequences of ischaemic brain injury and have disclosed the pathophysiological mechanisms involved. This procedure is aimed at triggering the activation of endogenous tolerance mechanism by delivering a subliminal ischaemic injury in the limbs, leading to a protective systemic response against ischaemic brain injury. Remote ischaemic conditioning (RIC) represents a potential neuroprotective strategy in stroke. 6Ī nationwide network of preclinical stroke research laboratories, Italian Stroke Organization (ISO) Basic Science, has been created to perform multicentre translational research projects on highly promising therapeutic strategies in experimental ischaemic stroke, with the aim of overcoming the barrier between the bench and bedside.
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5 Notably, it showed remarkable similarity with the results of a concomitant multicentre clinical trial on the same drug in human ischaemic stroke.
A first rigorous pRCT on natalizumab in experimental ischaemic stroke has been successfully performed in Europe using two different models in mice. 2–4 In multicentre pRCT, preclinical translational stroke research learns from the experience of clinical stroke research: a potential stroke therapy is tested under circumstances closer to the design and the rigour of a phase III randomised controlled clinical trial.
1 To improve the translation of treatment efficacy from bench to bedside, the new concept of multicentre preclinical randomised controlled trial (pRCT) is emerging as a necessary step before moving from animal modelling to clinical trial. Systematic reviews of experimental stroke research have consistently reported low-quality scores, negative publication bias and a paucity of data from female animals, aged animals or those with comorbidities, questioning the robustness and predictive value of single-laboratory preclinical experiments.
Numerous treatments, which were reported to improve outcome in experimental animal stroke models, ultimately failed in clinical trials.