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: 10677780
• 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/10677780
• 关键词: Address; Admission activity; 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; Dedications; Development Plans; Diagnosis; Disease; Diuresis; Diuretics; Dose; Drug Kinetics; Edema; Electrolytes; Ensure; Enteral; Environment; Evaluation; Excretory function; Exposure to; Funding; Furosemide; Gases; Goals; Harm Reduction; 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; Sampling; 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; pressure; primary outcome; programs; randomized trial; respiratory; response; secondary outcome; skill acquisition; 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.

项目总结/摘要 这个指导的以病人为导向的研究职业发展奖（K23）的目的是 提供尼古拉斯A. Bamat，医学博士，医学硕士，儿科讲师，佩雷尔曼医学院， 宾夕法尼亚大学（Penn）和费城儿童医院（CHOP）的指导， 培训和研究经验需要成为一个独立的临床研究者。他的长期职业生涯 我们的目标是通过领先的试验来确定证据， 基于药学实践。他近期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，Bamat博士和他的导师团队 我设计了一个职业发展计划，整合：（1）从成功的儿科医生那里得到密集的指导， 研究者;（2）临床试验、临床药理学和纵向数据分析方面的重点培训;以及（3） 呋塞米治疗重度支气管肺发育不良（BPD）策略的创新研究。 早产并发症是导致儿童残疾调整生命年损失的主要原因。 BPD或早产儿慢性肺病是最常见的主要发病率。BPD特别 对于严重BPD（sBPD）婴儿来说，这是毁灭性的，sBPD是最严重的级别。初始住院时间延长，共- 病态肺动脉高压、气管切开术延长通气和儿童死亡是常见的。 目前，没有药物治疗已被证明临床疗效，改善呼吸道疾病的过程中， sBPD尽管如此，药物暴露是常见的。袢利尿剂呋塞米是最常用的。 博士Bamat的指导研究将解决sBPD中使用呋塞米的关键知识差距。他将： (1)确定sBPD患者是否以及何时对呋塞米利尿耐受，（2）开发呋塞米人群 个体化给药方案的具有协变量分析的药代动力学模型，以及（3）应用 在（1）和（2）中获得的知识，以确定知情呋塞米的比较有效性 改善呼吸严重程度评分和降低发生率的治疗策略与标准治疗 与呋塞米相关的副作用这项研究将通过利用现有的 CHOP的慢性肺疾病计划，一个致力于sBPD婴儿的多学科转诊计划。 Bamat博士的研究结果将指导呋塞米治疗sBPD的策略，用于安慰剂的测试- 对照多中心试验，通过R系列奖资助，在他过渡到研究独立。的 描述的职业发展和研究活动将发生在宾夕法尼亚大学和CHOP，一个理想的环境， 这是为了培养下一代科学家进行NIH支持的面向患者的研究。

项目成果

Development, validation, and implementation of an UHPLC-MS/MS method for the quantitation of furosemide in infant urine samples.

• DOI: 10.1002/bmc.5262
• 发表时间: 2022-03
• 期刊: Biomedical chromatography : BMC
• 作者: Vedar C;Bamat NA;Zuppa AF;Reilly ME;Moorthy GS
• 通讯作者: Moorthy GS

Use of ventilation/perfusion mismatch to guide individualised CPAP level selection in preterm infants: a feasibility trial.

使用通气/灌注不匹配来指导早产儿个体化 CPAP 水平选择：可行性试验。

• DOI: 10.1136/archdischild-2022-324474
• 发表时间: 2023
• 期刊: Archives of disease in childhood. Fetal and neonatal edition
• 作者: Bamat,NicolasA;Orians,CarolynM;Abbasi,Soraya;Morley,ColinJ;RossRussell,Rob;Panitch,HowardB;Handley,SaraC;Foglia,ElizabethE;Posencheg,MichaelA;Kirpalani,Haresh
• 通讯作者: Kirpalani,Haresh