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Pharmacokinetic (PK) and Safety Study of Meropenem in Young Infants With Intra-abdominal Infections

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:
NCT00621192
First received: February 20, 2008
Last updated: May 15, 2014
Last verified: April 2014

February 20, 2008
May 15, 2014
June 2008
October 2009   (final data collection date for primary outcome measure)
  • 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.

    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) ] [ Designated as safety issue: Yes ]
  • Meropenem Clearance [ Time Frame: Up to 7-8hrs post drug administration ] [ 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 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) ] [ 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
Pharmacokinetics [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00621192 on ClinicalTrials.gov Archive Site
Not Provided
seizure frequency [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Pharmacokinetic (PK) and Safety Study of Meropenem in Young Infants With Intra-abdominal Infections
Multiple Dose Pharmacokinetic Study of Meropenem in Young Infants (<91 Days) With Suspected or Complicated Intra-abdominal Infections

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.

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:

  1. To characterize meropenem single-dose and multiple-dose PK in subjects with suspected and complicated intra-abdominal infections.
  2. To characterize the safety profile of meropenem in the treatment of suspected and complicated intra-abdominal infections.
  3. To assess collected efficacy data for meropenem for the treatment of suspected and complicated intra-abdominal infections.
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Necrotizing Enterocolitis
  • Intra-abdominal Infection
Drug: meropenem

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
Experimental: 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.

Intervention: Drug: meropenem
Cohen-Wolkowiez M, Poindexter B, Bidegain M, Weitkamp JH, Schelonka RL, Randolph DA, Ward RM, Wade K, Valencia G, Burchfield D, Arrieta A, Mehta V, Walsh M, Kantak A, Rasmussen M, Sullivan JE, Finer N, Rich W, Brozanski BS, van den Anker J, Blumer J, Laughon M, Watt KM, Kearns GL, Capparelli EV, Martz K, Berezny K, Benjamin DK Jr, Smith PB; Meropenem Study Team. Safety and effectiveness of meropenem in infants with suspected or complicated intra-abdominal infections. Clin Infect Dis. 2012 Dec;55(11):1495-502. doi: 10.1093/cid/cis758. Epub 2012 Sep 5.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
200
October 2009
October 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Written permission from parent or legal guardian
  2. Age younger than 91 days
  3. Likely to survive beyond the first 48 hours after enrollment
  4. Sufficient intravascular access (either peripheral or central) to receive study drug.

    AND ONE OF THE FOLLOWING

  5. 1) 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:

  1. Renal dysfunction evidenced by urine output <0.5 mL/hr/kg over the prior 24 hours
  2. Serum creatinine >1.7 mg/dL
  3. History of clinical seizures or EEG (Electroencephalogram) confirmed seizures
  4. Concomitant treatment with another carbapenem (ertapenem or imipenem) at the time of informed consent
  5. Any condition which would make the subject or the caregiver, in the opinion of the investigator, unsuitable for the study
Both
up to 90 Days
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00621192
HHSN267200700051C, HHSN267200700051C
Yes
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Not Provided
Principal Investigator: Danny Benjamin, MD, PhD, MPH Duke University
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP