Multicenter preclinical randomized controlled trials (pRCT)
The burden of stroke on society is substantial. Currently, therapy is limited to thrombolysis and thrombectomy. These facts clearly underline the need for novel therapeutic approaches. However, it has been challenging to translate experimental findings from preclinical observations to clinical application. These translational difficulties have resulted in several initiatives calling for vigorous experimental study designs including international preclinical trials. Multicenter preclinical randomized controlled trials (pRCT) should have a harmonized experimental protocol, and should be designed similar to randomized clinical trials with sample size calculation, randomization, blinding, cross-validation, and centralized study organization.
We have executed the first pRCT for IL-17 neutralization in experimental stroke. This study was carried out in Odense (Denmark), New York (USA), Hamburg (Germany) and Münster (Germany) using the temporal middle cerebral artery occlusion model (tMCAO). Following a predefined, randomized, and blinded protocol, we found that anti-IL-17A antibodies significantly reduced infarct size and mortality.
In summary, we show that we are in the position to successfully set up and implement pRCTs. With this experience we will in the future test the effectiveness of further new therapeutic strategies within pRCTs.