Preclinical randomized controlled multicenter trials (pRCT) in stroke research: a new and valid approach to improve translation?

Walter Balduini, Silvia Carloni, Mauro Cimino


Over the last decades, based on the improved knowledge of the pathophysiological mechanisms involved in ischemic stroke and neuronal degeneration, many experimental studies were carried out using drugs targeting the different steps of the degenerative process. Thus, drugs with anti-excitotoxic, antioxidant, anti-apoptotic and anti-inflammatory properties were investigated as potential protective therapeutic agents in animal models of stroke. In spite of the large evidence for neuroprotection of many of the tested compounds, a systematic review of the literature by Kidwell et al. reported that none of the more than 49 agents studied in clinical trials made the expected jump from bench to bedside (1). Therefore, since up to now new therapeutic agents have not been identified despite this intense research activity, thrombolysis with tissue plasminogen activator (tPA) remains the only clinically approved therapy for ischemic stroke (2). However, the discovery of new pharmacological tools is urgent because tPA has important contraindications which limit the number of stroke patients taking advantage from this treatment (3), leaving brain ischemia as one of the leading cause of death and disability.