Minor Endoscopic Sphincterotomy for Recurrent Acute Pancreatitis with Pancreas Divisum

小内镜下乳头括约肌切开术治疗复发性急性胰腺炎伴胰分裂

• 批准号: 9264121
• 负责人: Gregory A Cote
• 金额: $ 35.06万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-25 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9264121
• 关键词: Anatomy; Biological; Biological Markers; Blinded; Blood Glucose; Budgets; Case Report Form; Clinical Trials; Clinical Trials Design; Cohort Studies; Collaborations; Data; Development; Disease; Dorsal; Drainage procedure; Early Intervention; Elastases; Endocrine; Endoscopic Retrograde Cholangiopancreatography; Endoscopic Sphincterotomy; Enrollment; Etiology; Event; Fasting; Funding; Future; General Population; Glycosylated hemoglobin A; Goals; Hospitalization; Incidence; Intervention; Magnetic Resonance Imaging; Malignant neoplasm of pancreas; Manuals; Measures; Minor; Monitor; Mutation; National Institute of Diabetes and Digestive and Kidney Diseases; Natural History; Obstruction; Opiates; Outcome; Outcome Assessment; Outcome Measure; Outcome Study; Pain; Pancreas; Pancreatic duct; Pancreatitis; Patient Care; Patient-Focused Outcomes; Patients; Perceived quality of life; Predisposition; Procedures; Protocols documentation; Quality of life; Randomized; Recurrence; Research Infrastructure; Resources; Risk; Risk Factors; Role; Safety; Sample Size; Sampling; Scientist; Side; Single-Blind Study; Site; Stenosis; Therapeutic; Time; Training; Ultrasonography; acute pancreatitis; biobank; burden of illness; chronic pancreatitis; clinical care; clinically relevant; cohort; density; disability; disease natural history; follow-up; gastrointestinal; genetic predictors; high risk; impression; instrument; novel; open label; operation; pressure; primary outcome; randomized trial; repository; response; secondary outcome; sham-controlled study; tongue papilla; treatment group

Project summary Acute pancreatitis is among the most common gastrointestinal causes for hospitalization in the U.S. Roughly one in five patients with acute pancreatitis will have recurrent bouts. Recurrent acute pancreatitis (RAP) is a strong risk factor for progression to chronic pancreatitis, an irreversible fibroinflammatory disease that greatly impacts quality of life, and is also a risk factor for pancreatic cancer. Increased intraductal pressure is an accepted cause for precipitating an episode of acute pancreatitis. Pancreas divisum, seen in 7-10% of the general population, occurs when the dorsal and ventral pancreatic ducts have incomplete or nonexistent fusion during early embryologic development. Using this rationale, endoscopists often perform endoscopic retrograde cholangiopancreatography (ERCP) with minor papilla sphincterotomy (miES) in patients who have idiopathic RAP (iRAP) and pancreas divisum with a goal to reduce subsequent attack(s). This practice remains highly controversial, due to major limitations in the available data which are derived almost exclusively from small, retrospective cohort studies with inconsistent and subjective outcomes. This is one of the highest risk indications for ERCP, having post-ERCP pancreatitis rates of 10-20%. A full scale, well-designed clinical trial with adequate follow-up and blinded treatment allocation is clearly needed to empirically evaluate the efficacy of miES in the setting of iRAP and pancreas divisum, including quantifying the cumulative benefit of this intervention on disease burden and to study its relationship with its natural history. Capitalizing on the existing infrastructure of the recently completed EPISOD trial and NAPS2, we propose a sham-controlled, single blind with a blinded outcome assessment, randomized trial evaluating the impact of miES on the natural history of iRAP in patients with pancreas divisum. The primary outcome is reducing the risk of subsequent acute pancreatitis (time-to-event), with secondary outcome measures being the change in density of attacks, patient-centered outcomes, and progression to chronic pancreatitis. By having an adequate sample size to measure the benefit of ERCP, we will be able to definitively establish the therapeutic role of ERCP in patients with iRAP and pancreas divisum. A biorepository will be established for future exploratory studies of novel risk factors for recurrent acute pancreatitis, progression to chronic pancreatitis and its sequelae, and factors associated with response to miES. Patients fulfilling the entry criteria but refusing enrollment into the randomized trial will be enrolled into an observational cohort. Irrespective of the outcome, this study will have an immediate impact on patient care by confirming or refuting the therapeutic role of ERCP in patients with iRAP and pancreas divisum.

项目概要 急性胰腺炎是美国住院最常见的胃肠道原因之一。 大约五分之一的急性胰腺炎患者会反复发作。复发性急性胰腺炎 (RAP) 是进展为慢性胰腺炎的一个强烈危险因素，慢性胰腺炎是一种不可逆的纤维炎症性疾病 这极大地影响了生活质量，也是胰腺癌的危险因素。导管内压力增加 是引发急性胰腺炎发作的公认原因。胰腺分裂，见于 7-10% 一般人群，当背侧和腹侧胰管融合不完全或不存在时发生 在早期胚胎发育期间。利用这一原理，内窥镜医师经常进行内窥镜逆行手术 特发性胆胰管造影 (ERCP) 联合小乳头括约肌切开术 (mES) RAP (iRAP) 和胰腺分裂，目标是减少后续攻击。这种做法至今仍被高度重视 由于可用数据的主要局限性，这些数据几乎完全来自小规模、 回顾性队列研究的结果不一致且主观。这是风险最高的之一 ERCP 的适应症，ERCP 后胰腺炎发生率为 10-20%。全面、精心设计的临床试验 显然需要充分的随访和盲法治疗分配来凭经验评估疗效 miES 在 iRAP 和胰腺分裂的背景下的研究，包括量化这种累积效益 对疾病负担进行干预并研究其与其自然史的关系。 利用最近完成的 EPISOD 试验和 NAPS2 的现有基础设施，我们 提出一项假对照、单盲和盲法结果评估的随机试验，评估 miES 对胰腺分裂患者 iRAP 自然史的影响。主要结果是 降低随后发生急性胰腺炎的风险（事件发生时间），次要结果指标是 发作密度的变化、以患者为中心的结果以及慢性胰腺炎的进展。通过拥有 如果有足够的样本量来衡量 ERCP 的益处，我们将能够明确地确定 ERCP 在 iRAP 和胰腺分裂患者中的治疗作用。将建立一个生物样本库 未来对复发性急性胰腺炎、进展为慢性胰腺炎的新危险因素的探索性研究 胰腺炎及其后遗症，以及与 miES 反应相关的因素。符合入组标准的患者 但拒绝参加随机试验的人将被纳入观察队列。不论 结果，这项研究将通过确认或反驳治疗作用对患者护理产生直接影响 iRAP 和胰腺分裂患者的 ERCP 治疗。