Multiple Dose Pharmacokinetic Study of Meropenem in Young Infants (<91 Days) With Suspected or Complicated Intra-abdominal Infections
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 200
- 试验地点
- 26
- 主要终点
- Key Safety Endpoints
研究概览
简要总结
Meropenem is an antibiotic that is commonly used to treat serious infections. Although it is used in premature and young infants, the correct dose is not known. The purpose of this study is to determine the correct dose and the safety of meropenem for the treatment of complicated intra-abdominal infections in these young babies.
详细描述
This study will evaluate the safety, tolerability and Pharmacokinetics - Pharmacodynamics (PK-PD) of meropenem in infants <91 days of age with suspected and complicated intra-abdominal infections.
The specific aims of this trial are:
- To characterize meropenem single-dose and multiple-dose PK in subjects with suspected and complicated intra-abdominal infections.
- To characterize the safety profile of meropenem in the treatment of suspected and complicated intra-abdominal infections.
- To assess collected efficacy data for meropenem for the treatment of suspected and complicated intra-abdominal infections.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 90 Days（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written permission from parent or legal guardian
- •Age younger than 91 days
- •Likely to survive beyond the first 48 hours after enrollment
- •Sufficient intravascular access (either peripheral or central) to receive study drug.
- •AND ONE OF THE FOLLOWING
- •Physical, radiological, and/or bacteriological findings of a complicated intra-abdominal infection. These include peritonitis, NEC (Necrotizing Enterocolitis) Grade II or higher by Bell's criteria, Hirschsprung's disease with perforation, spontaneous perforation, meconium ileus with perforation, bowel obstruction with perforation, as evidenced by free peritoneal air on abdominal radiograph, intestinal pneumatosis or portal venous gas on abdominal radiographic examination.
- •OR 2) Possible NEC OR 3) Otherwise receiving meropenem per local standard of care
- •Exclusion criteria:
- •Renal dysfunction evidenced by urine output <0.5 mL/hr/kg over the prior 24 hours
- •Serum creatinine >1.7 mg/dL
- •History of clinical seizures or EEG (Electroencephalogram) confirmed seizures
- •Concomitant treatment with another carbapenem (ertapenem or imipenem) at the time of informed consent
- •Any condition which would make the subject or the caregiver, in the opinion of the investigator, unsuitable for the study
排除标准
- 未提供
研究组 & 干预措施
Meropenem
These
Participants were subdivided into the following four groups based on Gestational Age (GA) and Postnatal Age (PNA):
Group 1: GA at birth below 32 weeks - PNA <2 weeks; Group 2: GA at birth below 32 weeks - PNA ≥2 weeks and <91 days; Group 3: GA at birth 32 weeks or older - PNA <2 weeks; Group 4: GA at birth 32 weeks or older - PNA ≥2 weeks and <91 days.
干预措施: meropenem (Drug)
结局指标
主要结局
Key Safety Endpoints
时间窗: Up to 51 days (Adverse Events (AEs) were recorded from the time of informed consent until 72 hours following the last dose of study drug)
Safety assessments included death, seizure documentation (including correlation of serum meropenem level and seizures), strictures, perforation, wound dehiscence, short gut, development of extended beta lactamase infection, development of candidiasis, antimicrobial therapy failure
Deaths
时间窗: Up to 51 days (Recorded from the time of informed consent until 72 hours following the last dose of study drug)
Efficacy Success (Alive at Efficacy Visit,Last Culture (if Obtained) From Sterile Body Fluid is Negative for Bacteria (Except Staphylococcus Species) From Start of Study Drug Until Efficacy Visit,Presumptive Clinical Cure Score(PCCS) >7 at Efficacy Visit)
时间窗: Average of 12 days (3 to 21 days)
The PCCS was derived by comparing clinical signs and symptoms prior to administration of the first dose of study drug and study Day 28.The elements of the PCCS include Mean BP,Temp,PaO2(mmHg)/FiO2,Lowest serum pH,seizures,Urine output,Cardiovascular inotrope support,C-reactive protein (CRP)and Abdominal girth. Score - Asymptomatic to Asymptomatic 1;Asymptomatic to Worsening 0;Symptomatic to Worsening 0;Symptomatic to No change 0;Symptomatic to Improved 1;Symptomatic to Asymptomatic 1 If 7 or more of 10 signs received a score of 1, then the infant was considered a presumptive clinical cure. GA stands for Gestational Age and PNA stands for Postnatal Age.
Meropenem Clearance
时间窗: Up to 7-8hrs post drug administration
Given the limited availability of blood for Pharmacokinetic (PK) assessments in this population a sparse sampling approach was utilized. Subjects were assigned to one of two Dose 1 sample collection schedules, "PK-odd" and "PK-even" based on birth date to ensure collection of PK data throughout the dose interval. In addition, PK samples were collected around approximately the 5th dose. Subjects that did not have Dose 1 PK samples could have steady-state (Dose 5) using the Dose 5 PK collection schedule.
次要结局
未报告次要终点