Neurocognitive outcomes and changes in brain and CSF volume after treatment of post-infectious hydrocephalus in Ugandan infants by shunting or ETV/CPC: a randomized prospective trial

通过分流或 ETV/CPC 治疗乌干达婴儿感染后脑积水后的神经认知结果以及大脑和脑脊液体积的变化：一项随机前瞻性试验

• 批准号: 8992100
• 负责人: Abhaya V Kulkarni
• 金额: $ 28.38万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-22 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8992100
• 关键词: Africa; Africa South of the Sahara; Aftercare; Age-Months; Attention; Brain; Caring; Cauterization - action; Cellular Phone; Child; Childhood; Clinical Trials; Clinical Trials Data Monitoring Committees; Clinical Trials Design; Communities; Computer software; Country; Data; Data Base Management; Dependence; Developing Countries; Development; Enrollment; Equipoise; Failure; Foundations; Funding; Future; Grant; Growth; Head circumference; Health Personnel; Health Services Accessibility; Horns; Human Resources; Hydrocephalus; Image; Image Analysis; Improve Access; Infant; Infant Development; Infection; Intention; Investigation; Lead; Life; Measures; Mentors; Methods; Modality; Morbidity - disease rate; Neonatal; Neurocognitive; Outcome; Patients; Pediatric Hospitals; Phase; Physicians; Positioning Attribute; Postoperative Period; Public Health; Publishing; Randomized; Randomized Clinical Trials; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Recruitment Activity; Research; Research Infrastructure; Risk; Rural; Safety; Selection for Treatments; Seminal; Shunt Device; Site; Spinal Dysraphism; Structure of choroid plexus; Techniques; Technology; Testing; Training; Treatment Efficacy; Treatment outcome; Uganda; Ventriculostomy; Work; Writing; X-Ray Computed Tomography; arm; base; clinical investigation; clinical research site; cognitive testing; cohort; cone-beam computed tomography; cost effective; evidence base; follow-up; global health; medical specialties; member; mortality; novel; prevent; primary outcome; prospective; public health relevance; standard measure; tool

 DESCRIPTION (provided by applicant): We estimate 250,000 new infants develop hydrocephalus, most commonly following neonatal infection, in sub- Saharan Africa (SSA) each year. Most have poor access to treatment. We have developed and validated a novel operative treatment for infant hydrocephalus combining endoscopic third ventriculostomy and choroid plexus cauterization (ETV/CPC) that avoids shunt dependence in the majority. Our prior collaborative work at CURE Children's Hospital of Uganda (CCHU) supports equipoise between shunt placement and ETV/CPC in regard to 5-year survival and neurocognitive development. That ETV/CPC prevents shunt dependence among those with no urgent access for shunt malfunction is compelling, but we do not know which treatment optimizes brain development. Going forward with humanitarian efforts to improve access to care for PIH infants in SSA, we seek to confirm the optimal treatment selection paradigm. Using data from CT imaging, we have found that both brain and CSF volume are significant multivariate discriminators of neurocognitive outcome. This method is promising as an objective measure of hydrocephalus treatment efficacy. Preliminary data from our R-21 funded (1R21TW009612) randomized controlled trial (RCT) of ETV/CPC vs. shunt for PIH treatment (ClinicalTrials.gov registration NCT01936272) have shown no important differences (either by intention-to-treat or actual treatment received) at this point in regard to safety, efficacy, or developmental outcome, thereby supporting completion of the study and extension of the follow up through the period of maximal brain growth at 24 months of age. This R01 proposes to accomplish the following aims: 1) further develop CCHU as an independent site for clinical hydrocephalus research; 2) test the hypothesis that treatment of PIH by ETV/CPC is better than or equal to shunting in regard to neurocognitive development; 3) correlate brain/CSF volume metrics with neurocognitive development; 4) assess the utility of preoperative brain/CSF volume metrics to guide treatment selection. The RCT initiated in the R- 21 study will be extended and completed. Of 100 required patients, 77 have been enrolled thus far with 6- month follow-up in 40 and none lost to follow-up. For all 100 patients, CT imaging preoperatively and at 6, 12, and 24 months postoperatively will be completed for brain and CSF volumetric assessment. Neurocognitive assessment with the Bayley Scales of Infant Development (BSID-III) will also be completed preoperatively, and at 6, 12, and 24 months post-operatively. Neurocognitive outcome will be correlated with pre- and post- operative brain/CSF volumes and treatment modality. Changes in brain and CSF volumes will also be correlated with treatment modality. Completion of the study will determine whether there is an important difference in developmental outcome between these two treatments. Significantly, demonstrating superiority of ETV/CPC or no important difference will lead to selecting ETV/CPC as the preferred initial treatment. Research capacity at CCHU will be further developed.

 描述(由申请人提供)：我们估计撒哈拉以南非洲(SSA)每年有250,000名新婴儿发展为脑积水，最常见的是新生儿感染。大多数人很难获得治疗。我们开发并验证了一种新的手术治疗婴儿脑积水，联合内窥镜第三脑室造口和脉络丛烧灼术(ETV/CPC)，避免了大多数对分流的依赖。我们之前在乌干达治愈儿童医院(CCHU)的合作支持分流安置和ETV/CPC在5年生存和神经认知发展方面的平衡。ETV/CPC防止那些无法紧急进入分流故障的人依赖分流是令人信服的，但我们不知道哪种治疗方法能优化大脑发育。展望改善SSA妊高征儿护理机会的人道主义努力，我们寻求确认最佳治疗选择范例。使用来自CT成像的数据，我们发现大脑和脑脊液体积都是神经认知结果的显著多变量判别器。该方法作为脑积水治疗效果的客观衡量指标具有广阔的应用前景。我们R-21资助(1R21TW009612)的ETV/CPC与分流术治疗妊高征的随机对照试验(RCT)的初步数据(ClinicalTrials.gov注册NCT01936272)没有显示出在安全性、有效性或发育结局方面的重要差异(无论是意图治疗还是实际接受的治疗)，从而支持完成研究并将随访延长到24个月龄的脑最大生长期。本R01建议实现以下目标：1)进一步发展CCHU作为临床脑积水研究的独立场所；2)检验ETV/CPC治疗妊高征在神经认知发育方面优于或等于分流治疗的假设；3)将脑/脑脊液体积指标与神经认知发展相关；4)评估术前脑/脑脊液容量指标指导治疗选择的有效性。在R-21研究中启动的随机对照试验将得到延长和完成。在所需的100名患者中，到目前为止已有77名患者入选，其中40人获得了6个月的随访，没有一人失去随访。对于所有100名患者，将在术前、术后6个月、12个月和24个月完成CT成像，以进行脑和脑脊液容量评估。贝利婴儿发育量表(BSID-III)的神经认知评估也将在术前、术后6个月、12个月和24个月完成。神经认知结果将与手术前后的脑/脑脊液体积和治疗方式相关。脑和脑脊液容量的变化也将与治疗方式相关。这项研究的完成将确定这两种治疗方法在发育结果方面是否存在重要差异。值得注意的是，显示ETV/CPC的优越性或无显著差异将导致选择ETV/CPC作为首选的初始治疗方案。CCHU的研究能力将得到进一步发展。