Effect of early use of AbobotulinumtoxinA after stroke on spasticity progression: Protocol for a randomised controlled pilot study in adult subjects with moderate to severe upper limb spasticity (ONTIME pilot)

INTRODUCTION: Approximately 15 million people suffer a stroke annually, up to 40% of which may develop spasticity, which can result in impaired limb function, pain and associated involuntary movements affecting motor control. Robust clinical data on spasticity progression, associated symptoms development and functional impairment is scarce. Additionally, maximal duration of muscle tone reduction following botulinum toxin type A (BoNT-A) injections remains undetermined. The ONTIME pilot study aims to explore these issues and evaluate whether abobotulinumtoxinA 500 U (Dysport(®); Ipsen) administered intramuscularly within 12 weeks following stroke delays the appearance or progression of symptomatic (disabling) upper limb spasticity (ULS). METHODS: ONTIME is a 28-week, phase 4, randomised, double-blind, placebo-controlled, exploratory pilot study initiated at four centres across Malaysia, the Philippines, Singapore and Thailand. Subjects (n = 42) with moderate to severe ULS (modified Ashworth scale [MAS] score ≥2) in elbow flexors or pronators, wrist flexors, or finger flexors will be recruited. Subjects will be randomised 2:1 to abobotulinumtoxinA 500 U or placebo (single dose 2–12 weeks after first-ever stroke). Primary efficacy will be measured by time between initial injection and visit at which reinjection criteria (MAS score ≥2 in the primary targeted muscle group and appearance or reappearance of symptomatic ULS) are met. Follow-up visits will be 4-weekly to a maximum of 28 weeks. DISCUSSION: This pilot study will facilitate the design and sample size calculation of further confirmatory studies, and is expected to provide insights into the optimal management of post-stroke patients, including timing of BoNT-A therapy and follow-up duration.