权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Theophylline Prophylaxis during Hypothermia to Limit Neonatal Nephron Damage

低温期间预防茶碱以限制新生儿肾单位损伤

基本信息

批准号：
10656030
负责人：
JEFFREY L SEGAR
金额：
$ 25.85万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-04-01 至 2026-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10656030
关键词：
Acute Renal Failure with Renal Papillary Necrosis Address Adherence Adverse effects Age Years Aminophylline Asphyxia Neonatorum Attenuated Biological Markers Birth Blood flow Cessation of life Chronic Kidney Failure Clinical Data Clinical Trials Complex Complication Creatinine Data Data Analyses Data Collection Death Rate Development Diagnosis Disease Dose Drug Kinetics Effectiveness Enrollment Ensure Evaluation FDA approved Feasibility Studies Fluid Balance Foundations Functional disorder Future Goals Health Hospitalization Hour Hyperglycemia Hypertension Hypoxia Incidence Infant Injury Injury to Kidney Intervention Intervention Studies Intravenous Kidney Life Literature Measures Mechanical ventilation Methods Mission Morbidity - disease rate Multi-Institutional Clinical Trial National Institute of Diabetes and Digestive and Kidney Diseases Neonatal Nephrons Neurological outcome Organ Outcome Output Oxygen Patients Pharmacodynamics Pilot Projects Placebos Population Predisposition Pregnancy Prevention Procedures Process Prophylactic treatment Protocols documentation Publishing Regimen Renal function Reporting Research Risk Safety Sampling Seizures Serum Severities Tachycardia Telephone Testing Theophylline Therapeutic Therapeutic Trials Tubular formation Urine clinically relevant experience extracellular vesicles improved mortality natural hypothermia neonatal hypoxic-ischemic brain injury neonate novel novel marker novel therapeutics prevent primary outcome randomized trial recruit renal hypoxia response standard of care targeted treatment

项目摘要

PROJECT SUMMARY/ABSTRACT Acute kidney injury (AKI) is commonly seen in infants diagnosed with hypoxic-ischemic encephalopathy (HIE) and is associated with increased rates of morbidity and mortality. Currently, there are no approved therapies that target the prevention of AKI. Several small trials in infants with HIE suggest that a single dose of theophylline given soon after birth attenuates the development of AKI. However, these studies were not performed in infants being treated with therapeutic hypothermia (the current standard of care for moderate to severe HIE), and only reported short-term outcomes. Therefore, few clinicians use theophylline in the management of these patients. Our long-term goal is to undertake an appropriately powered multicenter clinical trial to test the hypothesis that for infants > 35 weeks gestation treated with therapeutic hypothermia for HIE, intravenous theophylline (or aminophylline) within the first 12 hours after birth will result in a decreased incidence and/or severity of AKI or death (composite primary outcome) and improved long-term (2 year) renal outcomes. Before the conduct of a large trial, the feasibility of implementing the intervention and ability to measure relevant clinical outcomes need to be demonstrated. Therefore, we propose a small pilot and feasibility clinical trial to i) evaluate recruitment, protocol adherence, and data collection procedures in a therapeutic trial of theophylline to decrease the incidence of AKI or death compared to placebo in infants with HIE being treated with therapeutic hypothermia; ii) evaluate the utility and applicability of established measures (serum creatinine, urine output, fluid balance) and novel, exploratory approaches (urine biomarkers, large renal tubular extracellular vesicles and renal oxygen saturation) to identify AKI in infants; and iii) determine theophylline pharmacokinetic, pharmacodynamic, safety and preliminary effectiveness profiles of two different theophylline dosing regimens in a therapeutic trial of theophylline to decrease the incidence of AKI or death compared to placebo. Using a mixed methods data analysis strategy to assess the research and intervention process and examine outcomes of the intervention, we will generate the requisite data to inform development and implementation of an appropriately powered study to determine whether theophylline attenuates the risk and severity of AKI in infants with HIE treated with therapeutic hypothermia.

项目总结/文摘