A Feasibility Study of Regadenoson for the Treatment of Acute Chest Syndrome

热加腺松治疗急性胸部综合征的可行性研究

• 批准号: 8313888
• 负责人: Joshua Jeffrey Field
• 金额: $ 34.1万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8313888
• 关键词: Address; Adult; Age; Agonist; Alloimmunization; Blood; Blood Vessels; Cause of Death; Cell Count; Cells; Chest Pain; Child; Clinical Protocols; Clinical Trials; Collaborations; Complication; Consent; Control Groups; Data; Data Coordinating Center; Disease; Dose; Drug Delivery Systems; Eligibility Determination; Enrollment; Etiology; Event; FDA approved; Feasibility Studies; Funding; Goals; Grant; Hereditary Disease; Hospitals; Hour; Human; Hypoxemia; Incidence; Individual; Infection; Inflammation; Infusion procedures; Institution; Ischemia; Isoantibodies; Laboratories; Length of Stay; Lung; Measurement; Measures; Mediator of activation protein; Modeling; Multi-Institutional Clinical Trial; Mus; National Heart, Lung, and Blood Institute; Outcome; Participant; Pathogenesis; Patients; Pharmaceutical Preparations; Phase; Physicians; Pilot Projects; Preparation; Principal Investigator; Pulmonary Fibrosis; Purinergic P1 Receptors; Randomized; Reaction; Reperfusion Injury; Research; Research Infrastructure; Research Personnel; Severities; Sickle Cell Anemia; Site; Symptoms; Testing; Tissues; Transfusion; acute chest syndrome; animal data; arm; base; clinical research site; design; effective therapy; experience; human data; innovation; insight; meetings; novel; phase 1 study; primary outcome; receptor; respiratory; safety study; sickling; trial comparing

DESCRIPTION (provided by applicant): Acute chest syndrome (ACS) is the leading cause of death for individuals with sickle cell disease (SCD). Current treatment for ACS is transfusion, which is complicated by alloimmunization, reactions, and infection. Additional therapies for ACS are desperately needed. The objective of this application is to determine the feasibility of conducting a clinical trial examining a novel agent, regadenoson, for the treatment of ACS in individuals with SCD. We have abundant preliminary data in murine models and patients with SCD to suggest that regadenoson, an adenosine2A receptor agonist, may interrupt ischemia/reperfusion injury (IRI) by targeting invariant NKT cells and decrease the severity of ACS episodes. We are currently performing a phase I dose finding and safety study of regadenoson in children and adults with SCD. Our ultimate goal is to extend the findings of the phase I study to the treatment of ACS. We plan to perform a multi-center, randomized phase IIb trial comparing regadenoson plus standard therapy versus standard therapy alone for ACS using length of stay as the primary outcome. We have assembled a consortium of seven institutions led by experienced SCD investigators to participate in this multi-center trial. This planning grant will be used to generate the data necessary to appropriately design the phase IIb study. In this application, we will: 1) determine whether sufficient numbers of patients with ACS can be accrued in our study consortium; and 2) measure the variance in length of stay among individuals with SCD and ACS who are receiving regadenoson. We will treat 20 participants with HbSS/HbS-thalassemia0, ages 14 to 70 years, who are admitted to the hospital for mild to moderate ACS episodes. Participants will receive a 48 hour infusion of a safe and biologically effective dose of regadenoson that will be added to standard therapy elected by the patients' physicians. We estimate that the incidence of ACS episodes in our consortium is 10 per month. Conservatively, we estimate that 1 patient will be enrolled for every 10 ACS episodes and over the 24 month funding period (enrolling about 1 patient per month) we will meet our accrual goal. Based on the data generated from this study, we plan to submit an R01 to support the phase IIb clinical trial. We anticipate that regadenoson may ultimately be used as an adjunct to transfusion therapy or may obviate the need for transfusion in some cases of ACS.

描述（由申请人提供）：急性胸部综合征（ACS）是镰状细胞疾病（SCD）的主要死因。当前对ACS的治疗是输血，这会因同种免疫，反应和感染而复杂。迫切需要ACS的其他疗法。该应用的目的是确定进行研究新药物Regadenoson的临床试验的可行性，以治疗SCD患者的ACS。在鼠模型和SCD患者中，我们拥有大量的初步数据，以表明腺苷2A受体激动剂可能会通过靶向不变的NKT细胞并减少ACS发作的严重程度来中断缺血/再灌注损伤（IRI）。我们目前正在对SCD儿童和成人进行I剂量发现和安全研究。我们的最终目标是将I期研究的发现扩展到ACS的治疗。我们计划进行多中心，随机的IIB试验，以比较Regadenoson加标准疗法与仅使用停留时间作为主要结果的AC的标准疗法进行比较。我们已经组建了一个由经验丰富的SCD研究人员领导的七个机构的财团，以参加这项多中心试验。该计划赠款将用于生成适当设计IIB期研究所需的数据。在此应用中，我们将：1）确定在我们的研究联盟中是否可以累积足够数量的AC患者； 2）衡量接受雷达尼森的SCD和ACS的个体之间住院时间的差异。我们将以14至70岁的HBSS/HBS-甲性疾病人的身份对20名参与者进行治疗，他们因轻度至中度ACS发作而被送往医院。参与者将收到48小时的安全性和生物学有效剂量的雷加纳斯森剂量，并将添加到患者医生选出的标准疗法中。我们估计我们财团中ACS发作的发病率为每月10个。保守地，我们估计每10个ACS发作和24个月的资金期（每月约1名患者）将入学1名患者，我们将达到我们的目标目标。根据本研究产生的数据，我们计划提交R01以支持IIB期临床试验。我们预计，雷加森最终可以用作输血疗法的辅助手段，或者在某些ACS中可能会消除输血的需求。