REPRIEVE - DCC

缓刑 - DCC

基本信息

批准号：
8730997
负责人：
UDO HOFFMANN
金额：
$ 135.91万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-08 至 2020-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8730997
关键词：
AIDS clinical trial group Acquired Immunodeficiency Syndrome Address Ancillary Study Angiography Archives Arteries Authorization documentation Bacterial Infections Biological Markers Biology Blood Blood Tests Blood Vessels Cardiac Cardiovascular Diseases Cardiovascular system Cessation of life Characteristics Clinical Clinical Data Clinical Trials Clinical Trials Data Monitoring Committees Coagulation Process Collaborations Collection Communication Companions Computers Controlled Clinical Trials Coronary Data Data Analyses Data Collection Data Coordinating Center Data Reporting Databases Diabetes Mellitus Disease Electronics Enrollment Ensure Event Grant Guidelines HIV Heart Heart Arrest Heart Diseases Hospitalization Image Immune Inflammation Inflammatory Lead Leadership Letters Liver Low-Density Lipoproteins Malignant Neoplasms Mediating Medicine Morphology Muscle Myocardial Infarction National Heart, Lung, and Blood Institute National Institute of Allergy and Infectious Disease Organization and Administration Participant Patients Peripheral Placebo Control Placebos Preparation Prevalence Prevention strategy Primary Prevention Principal Investigator Procedures Process Quality Control Randomized Research Research Design Risk Risk Factors Safety Site Stroke Study models System Testing Training United States Unstable angina Work X-Ray Computed Tomography adjudication antiretroviral therapy atherogenesis attenuation blood glucose regulation clinical Diagnosis clinical research site data acquisition data exchange data management data sharing design follow-up high risk immune activation indexing low density lipoprotein inhibitor meetings monocyte mortality novel pragmatic trial prevent protocol development public health relevance randomized trial tool treatment strategy vascular inflammation

AIDS clinical trial group Acquired Immunodeficiency Syndrome Address Ancillary Study Angiography Archives Arteries Authorization documentation Bacterial Infections Biological Markers Biology Blood Blood Tests Blood Vessels Cardiac Cardiovascular Diseases Cardiovascular system Cessation of life Characteristics Clinical Clinical Data Clinical Trials Clinical Trials Data Monitoring Committees Coagulation Process Collaborations Collection Communication Companions Computers Controlled Clinical Trials Coronary Data Data Analyses Data Collection Data Coordinating Center Data Reporting Databases Diabetes Mellitus Disease Electronics Enrollment Ensure Event Grant Guidelines HIV Heart Heart Arrest Heart Diseases Hospitalization Image Immune Inflammation Inflammatory Lead Leadership Letters Liver Low-Density Lipoproteins Malignant Neoplasms Mediating Medicine Morphology Muscle Myocardial Infarction National Heart, Lung, and Blood Institute National Institute of Allergy and Infectious Disease Organization and Administration Participant Patients Peripheral Placebo Control Placebos Preparation Prevalence Prevention strategy Primary Prevention Principal Investigator Procedures Process Quality Control Randomized Research Research Design Risk Risk Factors Safety Site Stroke Study models System Testing Training United States Unstable angina Work X-Ray Computed Tomography adjudication antiretroviral therapy atherogenesis attenuation blood glucose regulation clinical Diagnosis clinical research site data acquisition data exchange data management data sharing design follow-up high risk immune activation indexing low density lipoprotein inhibitor meetings monocyte mortality novel pragmatic trial prevent protocol development public health relevance randomized trial tool treatment strategy vascular inflammation

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项目摘要

DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) is increased 50-100% among HIV- infected patients, occurring often among relatively younger HIV patients despite minimal traditional risk factors, and normal LDL. Indeed, the mechanisms of atherogenesis in HIV are unique and relate to increased immune activation, as demonstrated by increased indices of monocyte activation and chemoattraction. Moreover, detailed coronary imaging by cardiac computed tomography angiography (CCTA) demonstrates a significantly increased prevalence of non-calcified plaque, with high risk morphological characteristics, including positive remodeling and low CT attenuation. Despite the significant increase in CVD among HIV-infected patients, no treatment strategies as yet exist to prevent this disease. Treatment with statins represents an attractive option to prevent CVD in HIV. Statins demonstrate potent effects to lower LDL and are known to uniquely reduce monocyte activation, chemoattraction and endothelial activation, potential pathogenetic mechanisms of atherogenesis in HIV. In this grant, we will perform a multicenter, randomized placebo-controlled clinical trial (REPRIEVE) of pitavastatin, as a primary prevention strategy for CVD in HIV. 5300 HIV-infected subjects without known heart disease and with LDL<130 mg/dL and Framingham Risk Score < 20 will be enrolled. Pitavastatin has been shown to safely and effectively lower LDL in HIV and is known to have minimal interactions with antiretroviral therapy. The primary endpoint will be the effects of statin therapy on major adverse cardiac events (MACE) including atherosclerotic or other CVD death, nonfatal myocardial infarction, unstable angina hospitalization, coronary or peripheral arterial revascularization, resuscitated cardiac arrest, nonfatal stroke. In addition, we will perform an embedded mechanistic study among 800 subjects using detailed CCTA imaging and sophisticated biomarker assessments to determine efficacy and mechanisms of statin therapy to reduce non-calcified plaque volume, and high risk morphological features. Change in specific inflammatory biomarkers, including monocyte activation, endothelial activation, arterial inflammation and coagulation, will be determined in the mechanistic study and then assessed with regard to MACE in the primary study, to provide critically needed information on the mechanisms of statin effects in HIV. Detailed safety indices, including effects on glucose homeostasis, liver and muscle will be determined, and effects on non CVD events will be explored The trial will be performed in collaboration with the AIDS Clinical Trial Group, as well as clinical research sites within the NIAID research network, including sites from the INSIGHT network. With 5300 planned participants the trial is well powered (90%) to detect a HR of 0.65, assuming a baseline event rate of 18/1000 PY. This novel trial will provide much needed information on a critical problem for HIV- infected patients and will serve as a model for the study of tailored primary prevention strategies for other inflammatory diseases in which immune mediated atherogenesis is an important contributing factor.

描述（由申请人提供）：艾滋病毒感染患者的心血管疾病（CVD）增加了50-100％，尽管传统危险因素很少，但在相对年轻的艾滋病毒患者中，通常发生在相对年轻的艾滋病毒患者中。实际上，HIV中动脉粥样硬化的机制是独一无二的，与免疫激活增加有关，如单核细胞激活和趋化收集指数的增加所证明。此外，心脏计算机层析成像造影术（CCTA）的详细冠状动脉成像表明，非固定斑块的患病率显着增加，具有高风险的形态特征，包括阳性重塑和低CT衰减。尽管HIV感染的患者的CVD显着增加，但尚无治疗策略以预防这种疾病。他汀类药物的治疗是预防艾滋病毒中CVD的有吸引力的选择。他汀类药物表现出对降低LDL的有效作用，并且已知可以独特地降低单核细胞激活，趋化和内皮激活，HIV中动脉粥样硬化的潜在致病机制。在这笔赠款中，我们将执行Pitavastatin的多中心，随机的安慰剂对照临床试验（缓刑），作为HIV中CVD的主要预防策略。 5300名没有已知心脏病的HIV受试者，LDL <130 mg/dl和Framingham风险评分<20。已证明pitavastatin可以安全有效地降低HIV中的LDL，并且已知与抗逆转录病毒疗法的相互作用最少。主要终点将是他汀类药物治疗对重大不良心脏事件（MACE）的影响，包括动脉粥样硬化或其他CVD死亡，非致命性心肌信息，不稳定的心绞痛住院，冠状动脉或周围动脉血运重建，复苏心脏骤停，非致命性stroke。此外，我们将使用详细的CCTA成像和复杂的生物标志物评估对800名受试者进行嵌入式机械研究，以确定他汀类药物疗法的功效和机制，以减少非估计的牌匾量和高风险形态特征。特定炎症性生物标志物的变化，包括单核细胞激活，内皮激活，动脉炎症和凝结，将在机械研究中确定，然后在主要研究中对MACE进行评估，以提供有关HIV中汀类药物效应机制的迫切需要的信息。将确定详细的安全指标，包括对葡萄糖稳态，肝脏和肌肉的影响，将探讨对非CVD事件的影响，该试验将与AIDS临床试验组以及NIAID研究网络中的临床研究站点合作进行，包括Insight Network的网站。在5300名计划参与者的情况下，该试验的功率很好（90％），以检测0.65的HR，假设基线事件率为18/1000 PY。这项新型试验将为艾滋病毒感染患者提供有关关键问题的急需信息，并将作为研究针对其他炎症性疾病的量身定制的原发性预防策略的模型，在这些炎症性疾病中，免疫介导的动脉粥样硬化发生是重要的因素。