Lactoferrin Enhances Growth and Reduces Nosocomial Infection in Preterm Infants

乳铁蛋白促进早产儿生长并减少医院感染

基本信息

  • 批准号:
    7539082
  • 负责人:
  • 金额:
    $ 55.73万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2008
  • 资助国家:
    美国
  • 起止时间:
    2008-09-12 至 2009-08-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): This project aims to develop talactoferrin (TLF, recombinant human lactoferrin) as a therapeutic agent to treat prematurely born neonates. The treatment will be given orally shortly after birth to prevent nosocomial infections (NIs) due to abnormal bacterial invasion of neonatal intestinal epithelia and consequently to limit systemic bacteremia and necrotizing enterocolitis (NEC). The overall incidence of prospectively studied NIs in hospitalized neonates has been reported to be 10.8 NI/100 patients. The incidence increases with decreasing birth weight, being as high as 81.8 NI/100 patients in Very Low Birth Weight group (birth weight < 1500 g). Recent data from the National Institute of Child Health and Human Development-sponsored "Neonatal Network" indicated that 29% of infants born at 25 to 28 weeks' gestation and 46% of infants born at less than 25 weeks' gestation experience a serious NIs during hospitalization in the NICU. The most common NI sites were sepsis and NEC. We therefore focus development of TLF on providing a sustained way to prevent and treat consequences of NIs in infants born prematurely and weighing from 750 to 1500 g at birth. The study shall enroll a total of 396 infants in a double-blind, randomized prospective study where TLF or placebo will be administered, in addition to the standard of care, to preterm infants before 24 hours of age. The study shall consist of four study groups: 1) mother's milk + placebo, 2) mother's milk + TLF, 3) formula feeding + placebo, and 4) formula feeding + TLF. The Phase-I part of the study shall determine the safety of TLF (at a dose of 300 mg/kg) when administered orally for 30 days. Using the total of (4 x 30) = 120 patients, safety of TLF shall be evaluated by determining the incidence and severity of adverse clinical events including laboratory and radiographic abnormalities. It is anticipated that adverse events might not be related to TLF, but rather to preterm birth, and TLF may mitigate those complications of prematurity [e.g., bronchopulmonary dysplasia]. The subsequent, continuous Phase-II part of the study shall ascertain the efficacy of TLF to enhance post-natal growth and to attenuate the incidence of nosocomial infections (including bacteremia, pneumonia, urinary infection, necrotizing enterocolitis [NEC] plus "NEC scares", and meningitis). All 396 patients recruited into the study (Phase I and Phase II) shall be used to evaluate efficacy of TLF. The Primary Endpoint shall be the time to regain birth weight, daily weight gain, and number of days to hospital discharge, Incidence of nosocomial infections [late-onset bacteremia, pneumonia, necrotizing enterocolitis, urinary tract infection, and meningitis] and incidence of "NEC Scares", "neonatal sepsis syndrome" or "systemic inflammatory response syndrome" without proven evidence of infection. Additionally, Secondary Efficacy Parameters shall evaluate the number of days on mechanical ventilation and/or nasal positive airway pressure, number of days on supplemental oxygen, and overall morbidity and mortality (%). A consortium of clinical centers has been formed to ensure adequate number of patients and the rate of recruitment to complete the project within 2 years from its initiation. The consortium includes the Southern Illinois University School of Medicine (St. John's Children's Hospital), The University of Louisville (Kosair Children's Hospital and the University of Louisville Hospital) and University of Southern California (Children's Hospital of Los Angeles and Hollywood Presbyterian Medical Center). Effectiveness of TLF in controlling NIs in neonates would likely find a logical extension to other populations of patients. More than 2,000,000 NIs occur each year in the USA (in infants and adults). This represents a major unmet medical need as well as a significant market. Marketing approval for TLF to treat NIs would be of great benefit to the patients and the community, and would also be of a substantial commercial value. PUBLIC HEALTH RELEVANCE: This proposed clinical study aims to determine the efficacy of orally administered talactoferrin (TLF, human recombinant lactoferrin) in preventing nosocomial infections (NIs) and their sequelae (such as sepsis, necrotizing enterocolitis [NEC], pneumonia, etc.) in infants born prematurely (and having a body-weight range from 750 to 1500 g). The overall incidence of prospectively studied NIs in hospitalized neonates was reported to be 10.8 NI/100 patients (Hentschel 1999). The incidence increases with decreasing birth weight, being as high as 81.8 NI/100 patients in Very Low Birth Weight group (birth weight < 1500 g). Recent data from the National Institute of Child Health and Human Development-sponsored "Neonatal Network" indicated that 29% of infants born at 25 to 28 weeks' gestation and 46% of infants born at less than 25 weeks' gestation experience a serious NIs during hospitalization in the NICU. The most common NI were sepsis and NEC. We therefore focus development of TLF on providing a sustained way to prevent and treat consequences of NIs in infants born prematurely and weighing from 750 to 1500 g at birth. In general, morbidity and mortality from NIs is enormous. In the US, more than 2,000,000 NIs [in infants and adults] occur each year, and 50% to 60% are caused by resistant organisms (Polin 2003). Once demonstrated to be efficacious, the use of oral TLF would be readily applicable for use across the range of age and indications of hospital patients.
项目描述(由申请人提供):本项目旨在开发重组人乳铁蛋白(talactoferrin, TLF)作为治疗早产新生儿的药物。该治疗将在出生后不久口服,以预防新生儿肠上皮细胞异常细菌侵袭引起的院内感染(NIs),从而限制全体性菌血症和坏死性小肠结肠炎(NEC)。据报道,住院新生儿中前瞻性研究的NIs总发病率为10.8 NI/100例患者。发病率随出生体重的降低而增加,极低出生体重组(出生体重< 1500 g)的发病率高达81.8 NI/100。由国家儿童健康和人类发展研究所赞助的“新生儿网络”的最新数据表明,29%的妊娠25至28周出生的婴儿和46%的妊娠不到25周出生的婴儿在新生儿重症监护室住院期间经历过严重的NIs。最常见的NI部位是败血症和NEC。因此,我们将TLF的发展重点放在提供一种持续的方法,以预防和治疗出生时体重在750至1500克之间的早产儿的NIs后果。该研究将在一项双盲、随机前瞻性研究中招募396名婴儿,在标准护理之外,将对24小时前的早产儿施用TLF或安慰剂。本研究将包括四个研究组:1)母乳+安慰剂,2)母乳+ TLF, 3)配方奶喂养+安慰剂,4)配方奶喂养+ TLF。研究的i期部分将确定TLF(剂量为300 mg/kg)口服30天的安全性。总共(4 × 30) = 120例患者,通过确定不良临床事件(包括实验室和影像学异常)的发生率和严重程度来评估TLF的安全性。预计不良事件可能与TLF无关,而与早产有关,TLF可能减轻早产并发症[如支气管肺发育不良]。后续持续的ii期研究将确定TLF在促进产后生长和降低院内感染(包括菌血症、肺炎、尿路感染、坏死性小肠结肠炎(NEC)加“NEC恐慌”和脑膜炎)发生率方面的疗效。所有396名患者(I期和II期)被纳入研究,以评估TLF的疗效。主要终点为恢复出生体重的时间、每日体重增加的时间、出院天数、院内感染(迟发性菌血症、肺炎、坏死性小肠结肠炎、尿路感染和脑膜炎)的发生率以及无感染证据的“NEC恐慌”、“新生儿败血症综合征”或“全身性炎症反应综合征”的发生率。此外,次要疗效参数应评估机械通气和/或鼻气道正压通气的天数、补充氧气的天数以及总体发病率和死亡率(%)。已经成立了一个临床中心联盟,以确保足够的患者数量和招募率,以便在启动后两年内完成该项目。该联盟包括南伊利诺伊大学医学院(圣约翰儿童医院)、路易斯维尔大学(Kosair儿童医院和路易斯维尔大学医院)和南加州大学(洛杉矶儿童医院和好莱坞长老会医疗中心)。TLF在控制新生儿NIs方面的有效性可能会在其他患者群体中得到合理的推广。美国每年发生超过200万例NIs(婴儿和成人)。这是一个重大的未满足的医疗需求,也是一个巨大的市场。批准TLF治疗NIs将给患者和社区带来巨大利益,也将具有巨大的商业价值。公共卫生相关性:本临床研究旨在确定口服talactoferrin (TLF,重组人乳铁蛋白)预防早产婴儿(体重750 - 1500 g)院内感染(NIs)及其后遗症(如败血症、坏死性小肠结肠炎[NEC]、肺炎等)的疗效。据报道,住院新生儿中前瞻性研究的NIs总发病率为10.8 NI/100例(Hentschel 1999)。发病率随出生体重的降低而增加,极低出生体重组(出生体重< 1500 g)的发病率高达81.8 NI/100。由国家儿童健康和人类发展研究所赞助的“新生儿网络”的最新数据表明,29%的妊娠25至28周出生的婴儿和46%的妊娠不到25周出生的婴儿在新生儿重症监护室住院期间经历过严重的NIs。最常见的NI是败血症和NEC。因此,我们将TLF的发展重点放在提供一种持续的方法,以预防和治疗出生时体重在750至1500克之间的早产儿的NIs后果。一般来说,NIs的发病率和死亡率都很高。在美国,每年[在婴儿和成人中]发生200多万例新感染,其中50%至60%是由耐药生物引起的(Polin 2003)。一旦证明有效,口服TLF的使用将很容易适用于各种年龄和医院患者的适应症。

项目成果

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KAREL PETRAK其他文献

KAREL PETRAK的其他文献

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{{ truncateString('KAREL PETRAK', 18)}}的其他基金

Lactoferrin Enhances Growth and Reduces Nosocomial Infection in Preterm Infants
乳铁蛋白促进早产儿生长并减少医院感染
  • 批准号:
    7845186
  • 财政年份:
    2008
  • 资助金额:
    $ 55.73万
  • 项目类别:
Treatment of Sepsis with Talactoferrin
用 Talactoferrin 治疗脓毒症
  • 批准号:
    7681601
  • 财政年份:
    2007
  • 资助金额:
    $ 55.73万
  • 项目类别:
Treatment of Sepsis using Recombinant Human Lactoferrin
使用重组人乳铁蛋白治疗脓毒症
  • 批准号:
    7053288
  • 财政年份:
    2006
  • 资助金额:
    $ 55.73万
  • 项目类别:
Recombinant Lactoferrin and Necrotizing Enterocolitis
重组乳铁蛋白与坏死性小肠结肠炎
  • 批准号:
    6833584
  • 财政年份:
    2004
  • 资助金额:
    $ 55.73万
  • 项目类别:
Recombinant human lactoferrin to treat oral mucositis
重组人乳铁蛋白治疗口腔粘膜炎
  • 批准号:
    6792842
  • 财政年份:
    2004
  • 资助金额:
    $ 55.73万
  • 项目类别:
GENE DELIVERY SYSTEMS FOR BRONCHO-ALVEOLAR DISEASES
支气管肺泡疾病的基因传递系统
  • 批准号:
    2716895
  • 财政年份:
    1997
  • 资助金额:
    $ 55.73万
  • 项目类别:
GENE DELIVERY SYSTEMS FOR BRONCHIO-ALVEOLAR DISEASE
支气管肺泡疾病的基因递送系统
  • 批准号:
    2030988
  • 财政年份:
    1997
  • 资助金额:
    $ 55.73万
  • 项目类别:
GENE MEDICINES FOR RHEUMATOID ARTHRITIS
治疗类风湿关节炎的基因药物
  • 批准号:
    2083696
  • 财政年份:
    1996
  • 资助金额:
    $ 55.73万
  • 项目类别:

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