Furosemide in severe bronchopulmonary dysplasia: comparative effectiveness of a duration and dosage informed treatment strategy

速尿治疗严重支气管肺发育不良：持续时间和剂量知情治疗策略的比较效果

• 批准号: 10457379
• 负责人: Nicolas Augusto Bamat
• 金额: $ 15.83万
• 依托单位: CHILDREN'S HOSP OF PHILADELPHIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-04 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10457379
• 关键词: Address; Adverse effects; Age; Award; Biological Availability; Blood; Bronchopulmonary Dysplasia; Caring; Cessation of life; Childhood; Chronic; Chronic lung disease; Clinical; Clinical Investigator; Clinical Pharmacology; Clinical Research; Clinical Trials; Complex; Data; Data Analyses; Development Plans; Diagnosis; Disease; Diuresis; Diuretics; Dose; Drug Kinetics; Edema; Electrolytes; Ensure; Enteral; Environment; Evaluation; Excretory function; Exposure to; Funding; Furosemide; Gases; Goals; Hospitalization; Hospitals; Hour; Impaired cognition; Infant; Intravenous; Kidney; Knowledge; Lead; Lung diseases; Measures; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Modeling; Morbidity - disease rate; Multicenter Trials; Neonatal; Oxygen; Pediatric Hospitals; Pediatrics; Pennsylvania; Pharmaceutical Preparations; Pharmacodynamics; Pharmacology; Pharmacotherapy; Philadelphia; Physiological; Placebo Control; Play; Population; Premature Birth; Premature Infant; Prospective cohort; Pulmonary Edema; Pulmonary Hypertension; Randomized; Regimen; Renal clearance function; Research; Research Activity; Research Personnel; Respiratory Disease; Role; Route; Safety; Scientist; Series; Severities; Severity of illness; Signal Transduction; Specific qualifier value; Stomach; Surrogate Markers; Testing; Therapeutic; Time; Tracheostomy procedure; Training; United States National Institutes of Health; Universities; Urine; absorption; animal data; career; career development; clinical efficacy; comorbidity; comparative effectiveness; design; disability-adjusted life years; dosage; evidence base; experience; flexibility; high risk infant; improved; improved outcome; infant outcome; innovation; instructor; medical schools; multidisciplinary; next generation; ototoxicity; patient oriented research; pharmacokinetic model; placebo controlled trial; premature; pressure; primary outcome; programs; randomized trial; respiratory; response; secondary outcome; skills; standard care; standard of care; targeted delivery; therapeutic target; treatment duration; treatment strategy; urinary; ventilation; years of life lost

PROJECT SUMMARY/ABSTRACT The purpose of this Mentored Patient-Oriented Research Career Development Award (K23) is to provide Nicolas A. Bamat, MD, MSCE, Instructor of Pediatrics at the Perelman School of Medicine at the University of Pennsylvania (Penn) and The Children’s Hospital of Philadelphia (CHOP) with the mentorship, training and research experience needed to become an independent clinical investigator. His long-term career goal is to improve outcomes for infants with neonatal lung disease by leading trials that identify evidence- based pharmacotherapeutic practices. His immediate career development goal is to acquire the skills needed to ensure a successful transition to research independence. To meet this goal, Dr. Bamat and his mentor team have devised a career development plan that integrates: (1) intensive mentorship from successful pediatric investigators; (2) focused training in clinical trials, clinical pharmacology and longitudinal data analysis; and (3) innovative research on furosemide treatment strategies for severe bronchopulmonary dysplasia (BPD). Complications of preterm birth are the leading pediatric contributor to disability-adjusted life years lost. BPD, or chronic lung disease of prematurity, is the most common major morbidity. BPD is particularly devastating for infants with severe BPD (sBPD), the worst severity class. Prolonged initial hospitalizations, co- morbid pulmonary hypertension, tracheostomy for prolonged ventilation and childhood death are common. Currently, no pharmacotherapies have proven clinical efficacy for improving respiratory disease course in sBPD. Despite this, medication exposures are common. The loop diuretic furosemide is most frequently used. Dr. Bamat’s mentored research will address key knowledge gaps surrounding furosemide use in sBPD. He will: (1) determine if and when tolerance to furosemide diuresis occurs in sBPD, (2) develop furosemide population pharmacokinetic models with covariate analysis for individualized dosage regimens, and (3) apply the knowledge gained in (1) and (2) to determine the comparative effectiveness of an informed furosemide treatment strategy versus standard of care for improving the respiratory severity score and decreasing the rate of furosemide-associated adverse effects. This research will be conducted by leveraging the existence of CHOP’s Chronic Lung Disease Program, a multidisciplinary referral program dedicated to infants with sBPD. Dr. Bamat’s findings will guide furosemide treatment strategies in sBPD, for testing in placebo- controlled multicenter trials, funded through R-series awards in his transition to research independence. The described career development and research activities will occur at Penn and CHOP, an ideal environment in which to train the next generation of scientists conducting NIH-supported patient-oriented research.

项目摘要/摘要 这个以患者为导向的导师研究职业发展奖(K23)的目的是 提供Nicolas A.Bamat，医学博士，MSCe，佩雷尔曼医学院儿科讲师 宾夕法尼亚大学(宾夕法尼亚大学)和费城儿童医院(CHOP)在指导下， 培训和研究经验需要成为一名独立的临床研究员。他长期的职业生涯 目标是通过领导试验来确定证据，以改善患有新生儿肺部疾病的婴儿的预后。 以药物治疗为基础的实践。他当前的职业发展目标是获得所需的技能 以确保成功过渡到研究独立。为了实现这一目标，巴马特博士和他的导师团队 我制定了职业发展计划，其中包括：(1)从成功的儿科医生那里获得密集的指导 研究人员；(2)临床试验、临床药理学和纵向数据分析方面的重点培训；和(3) 严重支气管肺发育不良(BPD)速尿治疗策略的创新研究。 早产并发症是导致残疾调整寿命年损失的主要儿科因素。 BPD，即早产儿慢性肺部疾病，是最常见的主要疾病。BPD特别是 对患有严重BPD(SBPD)的婴儿来说是毁灭性的，这是最严重的级别。延长首次住院时间，共同- 病理性肺动脉高压、气管切开术延长通气期和儿童死亡很常见。 目前，还没有药物疗法证明对改善呼吸道疾病病程有临床疗效。 圣彼得堡警察局。尽管如此，药物暴露还是很常见的。环状利尿剂速尿是最常用的。 巴马特博士的指导研究将解决有关速尿在sBPD中使用的关键知识空白。他将： (1)确定sBPD是否以及何时出现对速尿的耐受性；(2)发展速尿人群 采用协变量分析的个体化给药方案的药代动力学模型，以及(3)应用 在(1)和(2)中获得的知识，以确定知情速尿的比较有效性 改善呼吸严重程度评分和降低死亡率的治疗策略与护理标准 与速尿相关的不良反应。这项研究将利用存在的 CHOP的慢性肺病计划，这是一个专门为患有sBPD的婴儿提供的多学科转诊计划。 Bamat博士的发现将指导sBPD的速尿治疗策略，用于在安慰剂中进行测试- 受控多中心试验，在他向研究独立过渡的过程中，通过R系列奖项提供资金。这个 所描述的职业发展和研究活动将在宾夕法尼亚大学和CHOP大学进行，这是一个理想的环境 这是为了培训进行NIH支持的以患者为导向的研究的下一代科学家。