Perispinal Etanercept to improve STroke Outcomes (PESTO): Protocol for a multicenter, international, randomized placebo-controlled trial.

Rationale: A large proportion of stroke survivors will have long-lasting, debilitating neurological impairments, yet few efficacious medical treatment options are available. Etanercept inhibits binding of tumor necrosis factor to its receptor and is used in the treatment of inflammatory conditions. Perispinal subcutaneous injection followed by a supine, head down position may bypass the blood brain barrier. In observational studies and one small randomized controlled trial the majority of patients showed improvement in multiple post stroke impairments.
Aim: Perispinal Etanercept to improve STroke Outcomes (PESTO) investigates whether perispinal subcutaneous injection of etanercept improves quality of life and is safe in patients with chronic, disabling, effects of stroke.
Methods and Design: PESTO is a multicenter, international, randomized placebo-controlled trial. Adult participants with a history of stroke between 1 and 15 years before enrollment and a current modified Rankin scale between 2 and 5 who are otherwise eligible for etanercept are randomized 1:1 to single dose injection of etanercept or placebo.
Study Outcomes: The primary efficacy outcome is quality of life as measured using the Short Form 36 Health Inventory at day 28 after first injection. Safety outcomes include serious adverse events.
Sample Size Target: A total of 168 participants assuming an improvement of the SF-36 in 11% of participants in the control arm and in 30% of participants in the intervention arm, 80% power and 5% alpha.
Discussion: PESTO aims to provide level 1 evidence on the safety and efficacy of perispinal etanercept in patients with long-term disabling effects of stroke.
Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: This is an academic investigator- initiated trial:Vincent Thijs: VT reports no direct conflicts related to this publication. VT reports speaker fees for Amgen, Allergan, Astra Zeneca, Atricure, BMS, Bayer, Boehringer Ingelheim, Medtronic, unrelated to this publication. VT is on the editorial board for the following journals Annals of Neurology, Neurology, International Journal of Stroke and the European Stroke Journal. He is on the steering committee of the Librexia trial for which he receives modest compensation.Geoffrey Cloud: None Nigel Gilchrist: None Brooke Parsons: None Forum Tilvawala: None Jan Ho: NoneLara Ruthnam: None Vimal Stanislaus: None Nikola Spriggs: None Marion Walker: NonePhilip M Bath: PMB is Stroke Association Professor of Stroke Medicine and an emeritus NIHR Senior Investigator. He has consulted and received honoraria from CoMind, DiaMedica, Phagenesis and Roche.Leonid Churilov: None Julie Bernhardt: None