Pharmacokinetic (PK) and Safety Study of Meropenem in Young Infants With Intra-abdominal Infections (Meropenem PK)
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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Multiple Dose Pharmacokinetic Study of Meropenem in Young Infants (<91 Days) With Suspected or Complicated Intra-abdominal Infections|
- 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) [ Time Frame: Average of 12 days (3 to 21 days) ] [ Designated as safety issue: No ]
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.
- Deaths [ Time Frame: Up to 51 days (Recorded from the time of informed consent until 72 hours following the last dose of study drug) ] [ Designated as safety issue: Yes ]
- Meropenem Clearance [ Time Frame: 24 hours prior, post 1hr, post 4hrs, post 7-8hrs. ] [ Designated as safety issue: No ]Given the limited availability of blood for Pharmacokinetic (PK) assessments in this population a sparse sampling approach was utilized. Subjects were assigned into 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.
- Key Safety Endpoints [ Time Frame: 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) ] [ Designated as safety issue: Yes ]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
|Study Start Date:||June 2008|
|Study Completion Date:||October 2009|
|Primary Completion Date:||October 2009 (Final data collection date for primary outcome measure)|
Group 1: GA(Gestational Age) at birth below 32 weeks - PNA (Postnatal Age) < 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.
20 mg/kg every 12 hours in infants <32 weeks GA and PNA < 2 weeks 20 mg/kg every 8 hours in infants <32 weeks GA and PNA ≥ 2 weeks 20 mg/kg every 8 hours in infants ≥32 weeks GA and PNA < 2 weeks 30 mg/kg every 8 hours in infants ≥32 weeks GA and PNA ≥ 2 weeks
Other Name: Merrem
This study will evaluate the safety, tolerability and PK-PD (Pharmacokinetics - Pharmacodynamics) 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.
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|Principal Investigator:||Danny Benjamin, MD, PhD, MPH||Duke University|