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: 8931009
• 负责人: MARTIN LEE BLAKELY
• 金额: $ 1.11万
• 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 2016-04-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8931009
• 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; Data; Diagnosis; Education; Enrollment; Ensure; Equipoise; Event; Future; General Anesthesia; Gestational Age; Goals; Health; 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; individualized medicine; neonate; neurodevelopment; operation; patient safety; payment; prevent; primary outcome; programs; prospective; 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被评价以确定其安全性。早产儿特别容易受到未被识别的治疗危害。腹股沟疝（IH）修补术是早产儿最常进行的大手术，发病率为30-40%，目前尚不清楚是否应在新生儿重症监护室（NICU）出院前进行手术或延迟手术。早期肠内疝修补术可能会增加麻醉和心肺严重不良事件（SAE），而延迟肠内疝修补术可能会增加疝相关不良事件。越来越多的关注是早期全身麻醉暴露可能损害神经发育。提出的随机临床试验（RCT）将是第一个评价全身麻醉暴露时间对神经发育结局影响的试验。我们的目的是进行一项19个中心的随机对照试验，以确定早期IH修复术（在NICU出院前）或晚期IH修复术（在NICU出院后约5个月）是否是在NICU中诊断为腹股沟疝的早产儿更安全的手术方法。假设随机化率为60%，这得到了可行性试点RCT的支持，651名婴儿将在2.5年的时间内随机分配到早期或晚期IH修复。主要假设是，晚期IH修复术更安全，定义为入组后10个月内发生>1起SAE的婴儿比例绝对减少10%（相对风险= 0.66;早期修复术所需的伤害数量为10）。由对治疗组分配不知情的委员会裁定的主要结果是研究期间发生>1起SAE的婴儿比例。次要结局指标包括研究期间的住院天数（假设：晚期IH修复的中位住院天数减少3天），以及在选定的中心（n=200名婴儿）中，在2岁校正年龄时使用Bayley婴儿发育量表（BSID）第3版进行神经发育测试（假设：晚期IH修复的认知综合评分高0.4SD）。我们还将测量IH修复手术期间的非常规事件，这可能是SAE的基础。根据预先规定的患者特征（入组时），将通过频率论和保守贝叶斯方法检查治疗效果的潜在差异。该试验利用了儿科手术研究协作组织，这是一个致力于在儿科手术中进行前瞻性临床研究的合作组织。成功完成拟定的RCT将促进新生儿手术中未来的安全性研究。