{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T20:03:20Z","timestamp":1791576200291,"version":"4.3.4"},"reference-count":36,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Infants and toddlers with perinatal arterial ischemic stroke face a high risk for lifelong neuromotor impairments and multiple disabilities. Phase 3 clinical trial evidence is urgently needed to identify efficacious treatment to improve outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>The I-ACQUIRE Phase 3 trial (Perinatal Arterial Stroke: A Multisite RCT of Intensive Infant Rehabilitation) is a 15-site randomized clinical trial of 2 dosages of I-ACQUIRE, a multicomponent, therapist-delivered intervention including key components of constraint-induced movement therapy compared with usual and customary treatment. The trial recruited children 8 to 36 months old with parent-reported perinatal arterial ischemic stroke, hemiparesis, good health, and no prior botulinum toxin or constraint-induced movement therapy. Central 1:1:1 randomization assigned children to High-dose I-ACQUIRE (6-hour sessions, 5 days\/wk, 4 weeks), Moderate-dose I-ACQUIRE (3-hour sessions, 5 days\/wk, 4 weeks), and Usual and Customary Treatment. Blinded assessments at baseline, end-of-treatment, and 6-months later include the Emerging Behaviors Scale (success defined as % with gains \u22657 points), the primary outcome for unilateral skills on the paretic arm-and-hand; and the Mini-Assisting Hand Assessment, the secondary outcome for bimanual activities. Parents also rate children\u2019s motor skills, treatment responses, and stress. Statistical analyses include 2-sample binomial tests for group differences and linear mixed regression models. The registered trial adheres to international trial reporting guidelines and has a parent council.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>This study protocol describes intervention components plus training and monitoring of treatment fidelity. The trial recruited N=216 children; 198 completed baseline assessments, and 168 (85 boys and 83 girls) qualified for the modified intent-to-treat sample. The mean age was 18.0 (SD=7.6) months. A majority had right-sided paresis (70%); 51% had seizures\/epilepsy. Children varied widely in functional classification levels and parent ratings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>The trial sets a unique high threshold for efficacy and proposes sensitivity and exploratory analyses to consider differential response patterns to treatment. If 1 or both I-ACQUIRE dosages lead to significant improvements, then Phase 3 evidence will assist in infant\/toddler rehabilitation decision-making.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>REGISTRATION:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      ; Unique identifier: NCT03910075.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/strokeaha.125.053375","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T17:57:07Z","timestamp":1770400627000},"page":"614-621","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Perinatal Arterial Ischemic Stroke Phase 3 Trial Protocol for Intensive Infant-Toddler Rehabilitation (I-ACQUIRE)"],"prefix":"10.1161","volume":"57","clinical-trial-number":[{"clinical-trial-number":"nct03910075","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4630-7019","authenticated-orcid":true,"given":"Sharon Landesman","family":"Ramey","sequence":"first","affiliation":[{"name":"Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke (S.L.R., S.C.D., C.T.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8079-8977","authenticated-orcid":true,"given":"Warren D.","family":"Lo","sequence":"additional","affiliation":[{"name":"The Ohio State University, Columbus (W.D.L., J.C.H.)."},{"name":"Nationwide Children\u2019s Hospital, Columbus, OH (W.D.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie C.","family":"DeLuca","sequence":"additional","affiliation":[{"name":"Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke (S.L.R., S.C.D., C.T.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2241-1332","authenticated-orcid":true,"given":"Jill C.","family":"Heathcock","sequence":"additional","affiliation":[{"name":"The Ohio State University, Columbus (W.D.L., J.C.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy R.","family":"Darragh","sequence":"additional","affiliation":[{"name":"Virginia Commonwealth University, Richmond (A.R.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig T.","family":"Ramey","sequence":"additional","affiliation":[{"name":"Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke (S.L.R., S.C.D., C.T.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6726-3951","authenticated-orcid":true,"given":"Max","family":"Wintermark","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology, The University of Texas MD Anderson, Houston (M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9589-681X","authenticated-orcid":true,"given":"Renee H.","family":"Martin","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina, Charleston (R.H.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Conaway","sequence":"additional","affiliation":[{"name":"The University of Virginia, Charlottesville (M.R.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9446-8995","authenticated-orcid":true,"given":"Steven L.","family":"Wolf","sequence":"additional","affiliation":[{"name":"Medical University of South Carolina, Charleston (R.H.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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