Timing of Inguinal Hernia Repair in Premature Infants: A Randomized Trial

早产儿腹股沟疝修补术的时机：一项随机试验

• 批准号: 8737511
• 负责人: MARTIN LEE BLAKELY
• 金额: $ 63.41万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-22 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8737511
• 关键词: Academy; Adverse effects; Adverse event; Affect; Age; American; Anesthesia procedures; Bayesian Method; Blinded; Brain; Characteristics; Childhood; Chronic lung disease; Clinical Research; Cognitive; Cohort Studies; Commit; Data; Diagnosis; Education; Enrollment; Ensure; Equipoise; Event; Future; General Anesthesia; Gestational Age; Goals; Hernia; Imprisonment; Individual; Infant; Infant Development; Inguinal Hernia; Intervention; Length of Stay; Masks; Measures; Medical; Morbidity - disease rate; Mothers; Neonatal; Neonatal Intensive Care Units; Neonatology; Neurocognitive; Neurological outcome; Operative Surgical Procedures; Outcome; Outcome Measure; Patients; Pediatric Surgical Procedures; Perioperative; Postoperative Period; Premature Infant; Prenatal care; Procedures; Randomized; Randomized Clinical Trials; Relative (related person); Relative Risks; Research; Research Design; Research Personnel; Risk; Safety; Sedation procedure; Serious Adverse Event; Side; Site; Specific qualifier value; Surgeon; Testing; Therapeutic; Time; Training; adjudicate; capitate bone; cost; design; experience; follow-up; hazard; neonate; neurodevelopment; operation; patient safety; payment; prevent; primary outcome; programs; prospective; public health relevance; randomized trial; repaired; safety study; secondary outcome; treatment effect

DESCRIPTION (provided by applicant: Very few commonly used neonatal surgical therapies have been evaluated to determine their safety. Premature infants are especially vulnerable to unrecognized treatment hazards. Inguinal hernia (IH) repair is the most commonly performed major operation in premature infants, is associated with a 30-40% morbidity rate, and it is unknown whether the operation should occur prior to neonatal intensive care unit (NICU) discharge or be delayed. Early IH repair possibly increases anesthesia and cardiorespiratory serious adverse events (SAEs), whereas delayed IH repair possibly increases hernia-related adverse events. A growing concern is the possibility that early general anesthesia exposure impairs neurodevelopment. The randomized clinical trial (RCT) proposed will be the first trial to evaluate the effect of timing of general anesthesia exposure on neurodevelopmental outcomes. Our objective is to conduct a 19 center RCT to determine whether early IH repair (prior to NICU discharge) or late IH repair (~5 months after NICU discharge) is the safer surgical approach for premature infants who are diagnosed with an inguinal hernia while in the NICU. Assuming a 60% randomization rate, which is supported from a feasibility pilot RCT, 651 infants will be randomly assigned to early or late IH repair over a 2.5-year period. The primary hypothesis is that late IH repair is safer as defined by a 10% absolute reduction in the proportion of infants with >1 SAE (relative risk = 0.66; number needed to harm of 10 for early repair) within 10 months after enrollment. The primary outcome, as adjudicated by a committee masked to treatment group assignment, is the proportion of infants with >1 SAE during the study period. Secondary outcome measures include the number of hospital days during the study period (hypothesis: median 3 days less with late IH repair) and, in selected centers (n=200 infants), neurodevelopmental testing with the Bayley Scales of Infant Development (BSID), 3rd edition, at 2 years corrected age (hypothesis: 0.4SD higher Cognitive Composite score with late IH repair). We will also measure non-routine events during the IH repair operation, which may underlie SAEs. The potential differences in treatment effect according to pre-specified patient characteristics (at enrollment) will be examined by frequentist and conservative Bayesian methods. The trial is utilizing the Pediatric Surgery Research Collaborative, a cooperative group committed to performing prospective clinical studies in pediatric surgery. Successful completion of the RCT proposed will stimulate future safety studies within neonatal surgery.

描述(由申请人提供：很少有常用的新生儿外科治疗方法经过评估以确定其安全性。早产儿特别容易受到未经确认的治疗危险的影响。腹股沟疝修补术是早产儿最常见的大手术，发病率高达30%-40%，目前尚不清楚手术应该在新生儿重症监护病房(NICU)出院前进行还是推迟。早期IH修复可能会增加麻醉和心肺严重不良事件(SAE)，而延迟IH修复可能会增加与疝气相关的不良事件。越来越令人担忧的是，早期全身麻醉暴露可能会损害神经发育。建议的随机临床试验(RCT)将是第一个评估全身麻醉暴露时间对神经发育结果影响的试验。我们的目标是进行一项19中心的随机对照试验，以确定对于在NICU中被诊断为腹股沟疝的早产儿，早期IH修补术(NICU出院前)或晚期IH修补术(NICU出院后5个月)是更安全的手术方法。假设60%的随机化率，这是由可行性试验性随机对照试验支持的，651名婴儿将被随机分配到2.5年期间进行早期或晚期IH修复。主要的假设是，晚期IH修复更安全，其定义是在注册后10个月内患有&gt；1 SAE的婴儿比例绝对减少10%(相对风险=0.66；早期修复需要伤害10人)。主要结果是研究期间婴儿患有&gt；1 SAE的比例，这是由一个掩盖了治疗组分配的委员会做出的裁决。次级结果测量包括研究期间的住院天数(假设：接受晚期IH修复的中位数减少3天)，在选定的中心(n=200婴儿)，在校正的2岁年龄用贝利婴儿发育量表(BSID)第3版进行神经发育测试(假设：0.4SD较高的认知综合评分，采用晚期IH修复)。我们还将测量IH修复操作期间的非常规事件，这可能是SAE的基础。根据预先指定的患者特征(在登记时)的治疗效果的潜在差异将通过频数法和保守的贝叶斯方法进行检验。这项试验正在利用儿科外科研究合作组织，这是一个致力于在儿科外科领域进行前瞻性临床研究的合作组织。拟议中的随机对照试验的成功完成将促进未来新生儿手术的安全性研究。