Abstract Body: Background: Perinatal Arterial Ischemic Stroke (PAIS) affects about 1 in every 1100 – 1200 livebirths. It is the most prevalent form of ischemic stroke in children, and hemiparesis is the most common consequence. Currently there is limited intervention that is evidence-based to improve motor outcomes in the first 2 yrs of life, although RCTs of constraint-induced movement therapy (CIMT) have shown high treatment efficacy for older children with hemiparetic cerebral palsy. The I-ACQUIRE trial is the first large-scale phase 3 RCT of pediatric rehabilitation after stroke.

Objective: The Aims of the I-ACQUIRE trial are to test whether CIMT at moderate or high doses produce sustained improvement of unilateral and bilateral motor skills in the affected upper extremity (UE) when compared with usual and customary treatment.

Design: I-ACQUIRE is a 15-site study conducted through the NINDS StrokeNet. Infants and toddlers ages 8 months to 3 years who sustained PAIS are treated with a standardized CIMT protocol (I-ACQUIRE) by therapists for 3 or 6 hours/day, 5 days/week, for 4 weeks in a home-like environment. Subjects’ UE unilateral and bilateral motor skills are measured just before and after treatment, then 6 months later..

Results: The I-ACQUIRE trial completed sample enrollment of 216 children in October 2024; treatment and follow-up activities will be completed in 2025. During 5.5 years of operation 50 I-ACQUIRE therapists were trained and certified annually; 11 therapists have worked with the study since 2019. Fidelity of the I-ACQUIRE protocol is monitored each of the 4 weeks with weekly feedback from experts who score video samples and treatment logs. 45 blinded assessors were trained; 12 have worked since 2019. Total assessments to date are 695, 318 reliability checks have been performed on 2 outcome measures, and 4,274 video files are collected for review.

Conclusions: Stroke rehabilitation studies utilizing complex treatments must provide sufficient training resources to account for turn-over of therapists and assessors during a multi-year study. A standardized method for monitoring fidelity of all treatments is vital to ensure rigorous evaluation of treatment efficacy. Similarly, sufficient resources must be allocated to document that outcome assessments adhere to complex administration and scoring protocols. While these tasks add to the complexity and cost of the trial, they are critical for ensuring the scientific rigor and validity of study results.