Perinatal Arterial Stroke: A Multi-site RCT of Intensive Infant Rehabilitation (I-ACQUIRE)

围产期动脉中风：婴儿强化康复的多部位随机对照试验 (I-ACQUIRE)

• 批准号: 10115145
• 负责人: Warren David Lo
• 金额: $ 270.19万
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10115145
• 关键词: Address; Aftercare; Behavior; Blinded; Childhood; Clinical; Clinical Protocols; Clinical Trials; Clinical Trials Design; Code; Cognition; Data; Development; Diagnosis; Documentation; Dose; Double-Blind Method; Evidence based treatment; Family; Goals; Hand; Healthcare Systems; Home; Impairment; Incidence; Infant; Infant Care; Italy; MRI Scans; Maintenance; Monitor; Motor; Motor Skills; Neonatal ischemic stroke; Neurological status; Neurologist; Operant Conditioning; Outcome; Parents; Patients; Phase; Protocols documentation; Public Health; Quality of life; Randomized; Randomized Controlled Trials; Rehabilitation therapy; Research; Safety; Side; Site; Societies; Standardization; Statistical Data Interpretation; Stroke; Techniques; Testing; Training; Treatment outcome; United States National Institutes of Health; Upper Extremity; Variant; Videotape; blind; cognitive function; constraint induced movement therapy; cost; design; disability; dosage; efficacy evaluation; efficacy outcomes; evidence base; family burden; hemiparesis; implementation tool; improved; infant outcome; meetings; patient engagement; perinatal ischemic stroke; phase III trial; skills; standard of care; stroke incidence; theories; tool; treatment effect; treatment group; trial comparing

Perinatal arterial stroke (PAS) includes infants with neonatal arterial ischemic stroke and presumed perinatal arterial stroke and has an estimated incidence of 1 in 1150. The majority will develop hemiparesis, often resulting in lifelong and debilitating disability, including lowered cognition and quality of life. There are no evidence-based forms of rehabilitation designated as standard-of-care for these infants. We propose a Phase III trial to address this lack of evidence-based treatments. The I-ACQUIRE Trial is a rigorous, adequately powered, multi-site randomized controlled trial comparing 2 dosages of a pediatric rehabilitation - known as Infant ACQUIRE - to Usual and Customary treatment (U&CT). Prior studies of I- ACQUIRE show high safety, patient acceptability, and evidence of significant and enduring benefits. Briefly, I- ACQUIRE will be used to treat 8 – 24 mth old infants with PAS in either 3 hrs/day (Moderate Dose) or 6 hrs/day (High Dose), for 5 days/wk for 4 wks. Treatment occurs in a home or natural setting where operant conditioning techniques are applied to achieve goals paced for each infant. I-ACQUIRE includes the core features of pediatric Constraint-Induced Movement Therapy (CIMT). Standardized treatment at all sites is monitored weekly via a Fidelity of CIMT Implementation tool. Clinical Trial Design: 240 infants (N=80/group) will be randomly assigned to: 1) Moderate Dose I-ACQUIRE, 2) High Dose I-ACQUIRE, or 3) U&CT. (N=80). Double-blinded assessments occur at baseline, end of 4 wks of treatment, and 6 mos post-treatment. A Parent Council will be active throughout the trial, supporting NIH's goal of increased stakeholder engagement in clinical trials. The specific aims are: 1) Primary: Determine the efficacy of I-ACQUIRE at 2 dosage levels compared to U&CT to increase upper extremity skills on the hemiparetic side (using a minimal clinically meaningful threshold that is achieved at end of treatment and 6 mos later); 2) Secondary: Determine the efficacy of I- ACQUIRE at 2 dosage levels compared to U&CT to improve use of the hemiparetic upper extremity as an “assisting hand” in bimanual activities; and 3) Exploratory: Explore the association between I-ACQUIRE treatment at Moderate and/or High Doses and the infant's gross motor development and cognition (i.e., potential cross-domain effects of treatment). The Statistical Analysis Plan controls for multiple comparisons; after testing the major study hypotheses, sensitivity analyses will consider factors that may contribute to variation in treatment outcomes. Public Health Impact: Each year, an estimated 3400+ infants in the U.S. have PAS with high likelihood of lifelong impairment in neuromotor and often cognitive functioning resulting in a high cost burden for families, the healthcare system, and society. If I-ACQUIRE proves efficacious, then the field will have the critically needed Phase III confirmatory evidence and the specific clinical protocol needed to transform rehabilitation and improve clinical outcomes and quality of life for infants with PAS.

围产期动脉卒中（PAS）包括新生儿动脉缺血性卒中和假定的 围产期动脉卒中，估计发病率为1/1150。大多数人会出现轻偏瘫 经常导致终身和衰弱性残疾，包括认知能力和生活质量下降。没有 以证据为基础的康复形式被指定为这些婴儿的护理标准。 我们建议进行III期试验，以解决缺乏循证治疗的问题。I-ACQUIRE试验是 一项严格、充分把握度、多中心随机对照试验，比较了2种剂量的儿科 康复-被称为婴儿获取-到家庭和习惯治疗（U&CT）。先前的研究I- ACQUIRE显示出高安全性、患者可接受性以及显著和持久受益的证据。简单地说，我- ACQUIRE将用于治疗8 - 24个月大的PAS婴儿，每天3小时（中等剂量）或6小时 小时/天（高剂量），5天/周，持续4周。治疗发生在家庭或自然环境中， 应用调节技术以实现为每个婴儿设定的目标。I-ACQUIRE包括核心 儿童约束诱导运动疗法（CIMT）。所有研究中心的标准化治疗是 通过CIMT实施工具的Fidelity每周进行监测。临床试验设计：240例婴儿（N=80/组） 将被随机分配到：1）中等剂量I-ACQUIRE，2）高剂量I-ACQUIRE，或3）U&CT。（N=80）。 在基线、治疗4周结束和治疗后6个月进行双盲评估。父母 理事会将在整个试验过程中积极参与，支持NIH增加利益相关者参与的目标， 临床试验 具体目的是：1）主要：确定I-ACQUIRE在2个剂量水平下的疗效， U&CT增加偏瘫侧上肢技能（使用最小临床意义 治疗结束时和6个月后达到的阈值）; 2）次要：确定I- 与U&CT相比，ACQUIRE在2个剂量水平上改善了偏瘫上肢的使用， 探索性：探索I-ACQUIRE与“辅助手”的关系。 中剂量和/或高剂量治疗以及婴儿的粗大运动发育和认知（即， 治疗的潜在跨域效应）。统计分析计划控制多重比较; 在检验了主要的研究假设之后，敏感性分析将考虑可能导致 治疗结果的差异。 公共卫生影响：美国每年估计有3400多名婴儿患有PAS， 神经运动和认知功能的终身损伤导致家庭的高成本负担， 医疗系统和社会。如果I-ACQUIRE被证明是有效的，那么该领域将具有关键的 需要III期验证性证据和改造康复所需的具体临床方案， 改善PAS患儿临床结局和生活质量。