Pharmacokinetic (PK) and Safety Study of Meropenem in Young Infants With Intra-abdominal Infections
|ClinicalTrials.gov Identifier: NCT00621192|
Recruitment Status : Completed
First Posted : February 22, 2008
Results First Posted : November 29, 2011
Last Update Posted : April 17, 2015
|Condition or disease||Intervention/treatment||Phase|
|Necrotizing Enterocolitis Intra-abdominal Infection||Drug: meropenem||Phase 1 Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||200 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Multiple Dose Pharmacokinetic Study of Meropenem in Young Infants (<91 Days) With Suspected or Complicated Intra-abdominal Infections|
|Study Start Date :||June 2008|
|Actual Primary Completion Date :||October 2009|
|Actual Study Completion Date :||October 2009|
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.
Meropenem was administered concomitantly with compatible medications. Because an in-line filter is not appropriate due to drug binding, the 30 minute infusion was rate controlled by using appropriate infusion (syringe) pumps. Dosing and administration of other antimicrobial therapy (e.g., an aminoglycoside) was administered per local standard of care at the discretion of the infant's neonatologist. If there was a delay in the study drug shipment, sites were to use open-label meropenem to protect the safety of the participant.
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
- 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) ]
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.
- Deaths [ Time Frame: Up to 51 days (Recorded from the time of informed consent until 72 hours following the last dose of study drug) ]
- Meropenem Clearance [ Time Frame: 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.
- 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) ]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
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00621192
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|Principal Investigator:||Danny Benjamin, MD, PhD, MPH||Duke University|