1/2 A comparison of individualized vs. weight based protocols to treat vaso-occlusive episodes in Sickle Cell Disease (COMPARE VOE)

摘要 镰状细胞病是一种遗传性疾病，也是美国最常见的血红蛋白疾病 （美国）。它影响了大约9万到10万美国人，被列为第五大最常见的校长。 医疗补助的超级利用者住院诊断。疼痛性血管闭塞发作（VOE）， 疼痛（7/10或更大）至少4小时，除血管闭塞外没有其他解释，是 患者经历的SCD的最常见表现和急诊的最常见原因 部门（艾德）探访。没有标准的、基于证据的方法来治疗疼痛性VOE。2014年 美国国家心肺血液研究所（NHLBI）发布了“镰状病毒管理”的建议， 细胞疾病”，其中治疗VOE的建议是基于共识小组的专业知识， 证据建议包括使用患者特异性方案（针对患者的特定药物和剂量）。 个体患者）或标准VOE镇痛方案，其中标准VOE方案未定义。 我们实施了一个基于体重的镇痛方案作为“标准”VOE方案，并进行了试点 一项在两个ED纳入52例患者的随机临床试验（RCT），比较了患者特异性和基于体重的 镇痛方案;结果令人鼓舞，但由于患者和研究中心数量较少而受到限制。 我们提出了一项III期随机单盲（受试者设盲）临床试验来验证这一假设 患者特异性镇痛方案在临床上上级基于体重的镇痛方案， 因VOE而接受艾德就诊的SCD患者。这项五中心随机对照试验将460例成人SCD患者随机分组， 两个方案之一，以便在24小时内达到230例艾德访视VOE的目标 个月的注册期。230例患者的样本量将提供90%的把握度，用于临床检测14 mm 两种方案在主要终点方面存在显著差异， 艾德通过使用0-100 mm视觉模拟标尺进行放电。次要结局包括艾德住院时间， 住院、7天艾德回访和住院，我们将监测副作用和安全性。一 临床协调中心（CCC; Paula田边，PI）和数据协调中心（DCC; Huiman Barnhart，PI）将管理本试验。这个经验丰富的多专业团队将提供综合服务 对试验至关重要，包括临床和运营领导、研究中心管理、统计分析和数据 管理本试验产生的高水平证据将改变艾德治疗VOE的范式， 减少患有这种毁灭性并发症的SCD患者的疼痛。

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.