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）。它导致每年26亿美元的医疗保健费用，主要是由于这种疾病的更严重形式。缺乏任何治疗这种疾病的特定药物和识别将发展为更严重疾病的患者的预测因素导致了这一点。这项研究的长期目标是找到一种治疗这种疾病的药物，改善患者的预后，并降低医疗费用。根据我们对动物的经验和一个小型的人类受试者的初步研究，我们的假设和具体目标是：1。在诊断后72小时内给予喷替福林，可改善临床结局，并减少更严重形式的AP的发生。 2.喷替福林可降低炎症标志物的血液水平，这与临床结局的改善相关。本研究是一项新的探索性临床研究，研究了一种药物的作用，该药物在动物研究中已被证明在阻断AP的炎症反应中具有作用。这也是一项高回报的研究，将导致AP治疗的突破，并挑战单独支持治疗的古老建议。因此，它与R21赠款的NIH使命非常一致。该研究将有2组，每组64名患者，均患有AP，随机分配至药物或安慰剂，安慰剂看起来像药物，为期7天或直到他们出院时，如果出院是在入院后7天内。将在基线和连续5天或直至出院时（以先发生者为准）测量炎症标志物（CRP、IL-6、IL-8和TNF-α）的水平。组规模的确定基于先前的试点研究，以减少任何重要的不良结局，研究期间的脱落率为10%。2012年期间，263名AP患者入住该机构，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年时间内，可以招募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