Defining a Target Population to Effectively Test a Neuroprotective Drug

 There is that useless word again;'neuroprotection', which  gives no sense of urgency at all. Whereas the neuronal cascade of death sounds like something needing immediate attention.  When your doctor says neuroprotection didn't work or we don't have anything that stops the neuronal cascade of death.

Which one is going to get relatives screaming about incompetency? Neuroprotection says nothing, so doctors can skate by without telling their patients and relatives they just let billions of neurons die. The stroke doctor code of silence means no one needs to know how fucking bad stroke recovery is. Except survivors finally figure out they are screwed since no one in stroke tells them anything useful about recovery.

Defining a Target Population to Effectively Test a Neuroprotective Drug

Marta Olivé-Gadea

,

Manuel Requena

,

Daniel Campos

,

Alvaro Garcia-Tornel

,

Matías Deck

,

Marian Muchada

,

Sandra Boned

,

Noelia Rodríguez

,

Jesús Juega

,

David Rodríguez-Luna

,

Jorge Pagola

, … See all authors

Originally published11 Jan 2021https://doi.org/10.1161/STROKEAHA.120.032025Stroke. ;0

Abstract

Background and Purpose:

We aim to identify the subgroup of acute ischemic stroke patients with higher probabilities of benefiting from a potential neuroprotective drug using baseline outcome predictors and test whether different selection criteria strategies can improve detected treatment effect.

Methods:

We analyzed the association between final infarct volume (FIV), measured on 24- to 72-hour computed tomography, and National Institutes of Health Stroke Scale at discharge/day 5 of acute stroke patients who underwent endovascular treatment. Models were adjusted for age, sex, and affected hemisphere. We analyzed the impact of absolute (5–15 mL) and relative (33%) FIV reductions in the National Institutes of Health Stroke Scale in the whole population and in different subsets of patients selected according to baseline imaging criteria using computed tomography perfusion.

Results:

We analyzed 627 patients; association between FIV and 5-day National Institutes of Health Stroke Scale was best described with a quadratic function, with a regression coefficient β=1.56 ([95% CI, 1.45–1.67] P<0.001) in the adjusted analysis. In the models considering a fixed absolute (5/15 mL) FIV reduction, treatment effect was highest when patients with predicted larger FIV were excluded, whereas in a 33% FIV reduction model, treatment effect increased with the exclusion of patients with expected excellent outcomes.

Conclusions:

Patients either with excellent outcomes after endovascular thrombectomy or with large infarcts may dilute the treatment effect in stroke neuroprotective drug trials. (So you want to cherry pick your candidates?  You do know the goal is 100% recovery for all?)  Computed tomography perfusion on admission may help selecting adequate patients according to expected drug effect profile.