Oral Pentoxifylline vs. Placebo in Acute Pancreatitis: ... (short title)

口服己酮可可碱与安慰剂治疗急性胰腺炎：...（短标题）

• 批准号: 9070669
• 负责人: Santhi Swaroop Vege
• 金额: $ 19.88万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2017-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9070669
• 关键词: Accident and Emergency department; Accounting; Admission activity; Age; Alcoholic Hepatitis; Animals; Biological Sciences; Blood; Blood Cells; Blood Viscosity; Cessation of life; Classification; Clinic; Clinical; Clinical Research; Clinics and Hospitals; Cyclic Nucleotides; Data Discovery; Development; Diagnosis; Disease; Double-Blind Method; Dropout; Drops; Gland; Goals; Grant; Health; Health Care Costs; Hospitals; Hour; Human; IL8 gene; Infection; Inflammation; Inflammatory; Inflammatory Response; Institution; Interleukin-6; Intervention; Intervention Trial; Laboratory Markers; Lead; Length of Stay; Life; Measurement; Measures; Mediating; Mediator of activation protein; Methods; Microcirculation; Mission; Morbidity - disease rate; Necrosis; Oral; Organ failure; Outcome; Pancreas; Pathogenesis; Pathway interactions; Patient-Focused Outcomes; Patients; Pentoxifylline; Peripheral Vascular Diseases; Pharmaceutical Preparations; Pilot Projects; Placebo Control; Placebos; Platelet aggregation; Prospective Studies; Randomized; Recommendation; Recruitment Activity; Regulation; Reporting; Research Infrastructure; Resources; Role; Sample Size; Serum; Severities; Side; Subgroup; System; TNF gene; Testing; Time; United States National Institutes of Health; acute pancreatitis; adverse outcome; base; claudication; clinical predictors; cost; drug efficacy; drug mechanism; experience; gastrointestinal; high reward; human subject; improved; improved outcome; inflammatory marker; interest; mortality; novel; novel strategies; randomized trial

DESCRIPTION (provided by applicant): Acute pancreatitis (AP) is an inflammation of the pancreas gland and the most common gastrointestinal discharge diagnosis (approximately 280,000 admissions in 2009). It has resulted in $2.6 billion, annually, in health care costs, mainly due to the more serious forms of the disease. Lack of any specific drug to treat the condition and predictors to identify patients who will develop more serious forms of the disease contribute to this. Long-term objectives of the study are to find a drug to treat this disease, improve patient outcomes, and reduce the costs of health care. Based on our experience with animals and a small, human subjects pilot study, our hypothesis and specific aims are: 1. Pentoxifylline, administered within 72 hours of diagnosis, improves the clinical outcomes and decreases the occurrence of more serious forms of AP. 2. Pentoxifylline reduces the blood levels of inflammatory markers, which correlates with improvement in clinical outcomes. This study is a novel, exploratory clinical study of the effect of a drug that has a proven role in animal studies in blocking the inflammatory response in AP. It is also a high reward study that will lead to a breakthrough in the treatment of AP and challenge the age old recommendation of supportive treatment alone. Thus it aligns extremely well with the NIH mission of R21 grants. The study will have 2 groups of 64 patients each, all with AP, randomly assigned to either the drug or a placebo, which looks like the drug, for a period of 7 days or until the time they are discharged, if hospital discharge is within 7 days of admission. The levels of markers of inflammation (CRP, IL-6, IL-8 and TNF-a) will be measured at baseline and on 5 successive days or until the time of discharge, whichever occurs earlier. Determination of group size was based on the previous pilot study to decrease any of the important adverse outcomes, providing for a dropout rate of 10% during the study. During 2012, 263 patients with AP were admitted to this institution, which possesses the needed infrastructure for successful completion of clinical drug intervention trials. In the stipulated period of 2 years by the NIH, the required number of patients for the study could be recruited.

描述（由申请人提供）： 急性胰腺炎 (AP) 是一种胰腺炎症，是最常见的胃肠道分泌物诊断（2009 年约有 280,000 例入院）。它每年造成 26 亿美元的医疗保健费用，主要是由于这种疾病的严重形式。缺乏任何特定药物来治疗这种疾病，也缺乏预测因素来识别将患上更严重疾病的患者。该研究的长期目标是找到治疗这种疾病的药物，改善患者的治疗效果，并降低医疗保健成本。根据我们对动物的经验和一项小型人类受试者试点研究，我们的假设和具体目标是： 1. 诊断后 72 小时内服用己酮可可碱，可改善临床结果并减少更严重的 AP 形式的发生。 2.己酮可可碱降低血液中炎症标志物的水平，这与临床结果的改善相关。这项研究是一项新颖的、探索性的临床研究，研究药物在阻断 AP 炎症反应方面的作用，该药物在动物研究中已被证明具有作用。这也是一项高回报的研究，将带来 AP 治疗的突破，并挑战单独支持治疗的古老建议。因此，它与 NIH R21 拨款的使命非常吻合。该研究将分为 2 组，每组 64 名患者，全部患有 AP，随机分配到该药物或安慰剂（看起来像该药物），为期 7 天，或者直到他们出院（如果出院时间在 6 天内）入学7天。炎症标记物（CRP、IL-6、IL-8 和 TNF-a）的水平将在基线和连续 5 天或直到出院时（以较早发生者为准）进行测量。小组规模的确定是基于先前的试点研究，以减少任何重要的不良后果，并规定研究期间的退出率为 10%。 2012年期间，该机构收治了263名AP患者，该机构拥有成功完成临床药物干预试验所需的基础设施。在NIH规定的2年期限内，可以招募到研究所需数量的患者。

项目成果

A single center randomized double blind controlled trial of pentoxifylline in acute pancreatitis: Challenges and opportunities.

• DOI: 10.1016/j.pan.2020.09.023
• 发表时间: 2020-12
• 期刊: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]
• 作者: Vege SS;Horibe M;Chari ST;Clemens MA;Loftus CG;Enders FT
• 通讯作者: Enders FT