Neuroprotection Is Unlikely to Be Effective in Humans Using Current Trial Designs

What we need to carry out in the laboratory and at the bedside are experiments. If our experiments have been positive in the laboratory but negative at the bedside, it is logical to me that at the bedside we need to better emulate the conditions under which the laboratory experiment turns out positive; in other words, we need to do the “rat experiment” in man. Those clinical studies that have adhered to this dictum1–3 have been the only positive clinical trials to date.Figure 1 depicts the general design of the rat transient middle cerebral artery occlusion model that is most often used to test neuroprotective drugs. It also depicts the general design of the sort of clinical trial that I postulate must be done to get positive results in stroke patients. There are 4 main areas where clinical trials have departed most from this model. In rats, we take pains to produce lesions of standardized severity in order to better detect a treatment effect; we start by giving the drug soon after the onset of stroke and then determine how much this time to treatment (TTT) can be lengthened; we use models of temporary rather than permanent arterial occlusion; and we increase doses of drug until we see a therapeutic effect. Figure 1. Proposed algorithm for studying neuroprotective drugs in laboratory animals and human stroke patients.These factors must all be addressed in the design of future clinical trials, and they are listed in Figure 2 along with …