2/2 A comparison of individualized vs. weight based protocols to treat vaso-occlusive episodes in Sickle Cell Disease (COMPARE VOE)

2/2 治疗镰状细胞病血管闭塞发作的个体化方案与基于体重的方案的比较（COMPARE VOE）

• 批准号: 10241400
• 负责人: Huiman X Barnhart
• 金额: $ 119.5万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-07 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10241400
• 关键词: Accident and Emergency department; Adult; Affect; African American; American; Analgesics; Authorization documentation; Blinded; Chronic Disease; Clinical; Clinical Trials; Clinical Trials Data Monitoring Committees; Collaborations; Collection; Companions; Complication; Computers; Consensus; Data; Data Collection; Data Coordinating Center; Data Reporting; Diagnosis; Disease; Dose; Emergency Department patient; Emergency department visit; Enrollment; Genetic Diseases; Goals; Good Clinical Practice; Healthcare; Hemoglobin; Hemoglobinopathies; Hospitalization; Hour; Leadership; Length of Stay; Letters; Level of Evidence; Measures; Medicaid; Medical; Monitor; National Heart, Lung, and Blood Institute; Pain; Patients; Phase; Population; Preparation; Principal Investigator; Procedures; Process; Protocols documentation; Publications; Quality Control; Randomized; Randomized Clinical Trials; Recommendation; Reporting; Research Design; Safety; Sample Size; Services; Shapes; Sickle Cell Anemia; Single-Blind Study; Site; Statistical Data Interpretation; System; Testing; Training; United States; Visual; Weight; Work; analog; arm; base; clinically significant; data integrity; data management; data quality; data sharing; electronic data; evidence base; experience; improved; individual patient; medical specialties; pain reduction; pain score; primary endpoint; primary outcome; protocol development; randomized trial; recruit; secondary outcome; side effect; tool

Abstract Sickle cell disease (SCD) is a genetic disorder and the most common hemoglobin disorder in the United States (U.S.). It affects an estimated 90,000-100,000 Americans and was ranked as the fifth most common principal diagnosis for Medicaid's super-utilizer hospital stays. Painful vaso-occlusive episodes (VOE), a new onset of pain (7/10 or greater) for at least four hours for which there is no other explanation than vaso-occlusion, are the most common manifestation of SCD experienced by patients and the most common reason for emergency department (ED) visits. There is no standard, evidence based approach to treating painful VOE. In 2014 the National Heart, Lung, and Blood Institute (NHLBI) released recommendations for the “Management of Sickle Cell Disease” where recommendations to treat VOE were based on consensus panel expertise due to lack of evidence. Recommendations included the use of a patient specific protocol (specific agents and doses for an individual patient) or a standard VOE analgesic protocol, where the standard VOE protocol was not defined. We implemented a weight-based analgesic protocol as a “standard” VOE protocol and conducted a pilot randomized clinical trial (RCT) at two EDs with 52 patients comparing the patient-specific and weight-based analgesic protocols; results were encouraging, however, limited due to small numbers of patients and sites. We propose a Phase III randomized and single-blinded (with subject blinded) clinical trial to test the hypothesis that the patient-specific analgesic protocol is clinically superior to the weight-based analgesic protocol for treating SCD patients with an ED visit due to VOE. This five-site RCT will randomize 460 adult SCD patients to one of the two protocols in order to have the target of 230 patients with an ED visit for VOE during the 24 month enrollment period. A sample size of 230 patients will provide 90% power for detecting a 14 mm clinically significant difference between the two protocols in the primary endpoint, pain score reduction from arrival in the ED to discharge by using a 0-100 mm visual analog scale. Secondary outcomes include ED length of stay, hospitalization, seven day return ED visits and hospitalizations and we will monitor side effects and safety. A Clinical Coordinating Center (CCC; Paula Tanabe, PI) and a Data Coordinating Center (DCC; Huiman Barnhart, PI) will manage this trial. This experienced multi-specialty team will deliver the integrated services vital to the trial, including clinical and operational leaderships, site management, statistical analysis and data management. High level evidence generated by this trial will shift the paradigm on treating VOE in the ED and decreasing the pain of SCD patients suffering from this devastating complication.

摘要 镰状细胞病(SCD)是一种遗传性疾病，是美国最常见的血红蛋白疾病 (美国)。据估计，它影响了9万至10万美国人，并被列为第五大最常见的本金 被诊断为医疗补助的超级公用事业住院。痛苦的血管闭塞发作(VOE)，新的发作 疼痛(7/10或更高)至少四个小时，除了血管闭塞之外没有其他解释，是 患者经历的SCD最常见的表现和最常见的急诊原因 部门(ED)访问。目前还没有一种标准的、基于证据的方法来治疗疼痛的VoE。2014年， 美国国家心肺血液研究所(NHLBI)发布了《镰刀的管理》建议 细胞疾病“，其中治疗VOE的建议是基于协商一致的小组专业知识，因为缺乏 证据。建议包括使用患者特定的方案(特定的药物和剂量 单个患者)或标准VOE止痛方案，其中没有定义标准VOE方案。 我们实施了一种基于权重的止痛方案，将其作为标准的VOE方案，并进行了试点 两个急诊室的随机临床试验(RCT)，52名患者，比较特定患者和基于体重的 止痛方案；结果令人鼓舞，但由于患者数量和部位较少，结果有限。 我们提出了一项第三阶段的随机、单盲(受试者盲)临床试验来检验这一假说。 患者特定的止痛方案在临床上优于基于重量的止痛方案 因VOE而进行ED访视治疗SCD患者。这项五点随机对照试验将460名成年SCD患者随机分为 两个方案之一，以使230名患者在24小时内接受VOE急诊 月注册期间。230名患者的样本大小将为临床检测14 mm提供90%的功率 两种方案在主要终点方面的显著差异，从到达 ED通过使用0-100 mm视觉模拟标尺进行放电。次要结果包括ED的住院时间， 住院，七天回访急诊室和住院治疗，我们将监测副作用和安全性。一个 临床协调中心(CCC；Paula Tanabe，PI)和数据协调中心(DCC；惠曼 巴恩哈特，PI)将管理这一试验。这支经验丰富的多专业团队将提供综合服务 对试验至关重要，包括临床和业务领导、现场管理、统计分析和数据 管理层。这项试验产生的高水平证据将改变急诊室治疗VOE的范式 减轻患有这种毁灭性并发症的SCD患者的痛苦。