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: 10356111
• 负责人: Warren David Lo
• 金额: $ 328.24万
• 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 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10356111
• 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)包括患有新生儿动脉缺血性卒中的婴儿和推测 围产期动脉卒中，估计发病率为1/1150。大多数人会发展成偏瘫， 往往导致终生和衰弱的残疾，包括认知和生活质量下降。没有 被指定为这些婴儿的标准护理的循证康复形式。 我们建议进行第三阶段试验，以解决这种缺乏循证治疗的问题。I-Acquires试验是一项 严格、动力充足的多部位随机对照试验，比较了两种剂量的儿科药物 康复--称为婴儿习得--通常和常规治疗(U&CT)。先前关于i-的研究- Acquires表现出高度的安全性、患者的可接受性以及显著和持久的益处。简单地说，我- Acquire将用于治疗8-24个月大的婴儿，每天3小时(中剂量)或6小时/天。 小时/天(大剂量)，5天/周，共4周。治疗在家庭或自然环境中进行， 调节技术被应用来实现为每个婴儿设定的目标。I-Acquire包括核心 儿童强迫诱导运动疗法的特点所有地点的标准化治疗都是 通过Fidelity of CIMT实施工具进行每周监控。临床试验设计：240例婴儿(N=80例/组) 随机分为：1)中剂量I-Acquire，2)高剂量I-Acquire，或3)U&CT。80例。 在基线、治疗4周末和治疗后6个月进行双盲评估。一位家长 委员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。 具体目标是：1)主要：测定两个剂量水平的I-Acquide的疗效，与 U&CT增强偏瘫侧上肢技能(使用最小的临床意义 在治疗结束和6个月后达到的阈值)；2)二级：确定I- 与超声和CT相比，在2个剂量水平下获取，以改善偏瘫上肢的使用 双工活动中的“帮手”；3)探索性：探索我--习得之间的联系 中剂量和/或高剂量治疗与婴儿的大运动发育和认知(即， 治疗的潜在跨域影响)。统计分析计划对多次比较的控制； 在检验了主要的研究假设之后，敏感度分析将考虑可能有助于 治疗结果的差异。 对公共健康的影响：据估计，美国每年有3400多名婴儿通过高危疾病 神经运动和认知功能的终生障碍会给家庭带来很高的成本负担， 医疗保健系统和社会。如果I-Acquire被证明是有效的，那么这个领域将拥有关键的 需要第三阶段确认性证据和具体的临床方案，以转变康复和 改善PAS患儿的临床结局和生活质量。