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

Sponsor:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT00621192

Purpose

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.

Condition	Intervention	Phase
Necrotizing Enterocolitis Intra-abdominal Infection	Drug: meropenem	Phase 1 Phase 2

Study Type:	Interventional
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

Resource links provided by NLM:

Drug Information available for: Meropenem

U.S. FDA Resources

Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:

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

Enrollment:	200
Study Start Date:	June 2008
Study Completion Date:	October 2009
Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 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.	Drug: meropenem 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

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	up to 90 Days
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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
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:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00621192

Show 26 Study Locations

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Principal Investigator:

Danny Benjamin, MD, PhD, MPH

Duke University

More Information

No publications provided

Responsible Party:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT00621192 History of Changes
Other Study ID Numbers:	HHSN267200700051C, HHSN267200700051C
Study First Received:	February 20, 2008
Results First Received:	October 20, 2011
Last Updated:	February 24, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

meropenem
infants
intra-abdominal infection
pharmacokinetics
safety

Additional relevant MeSH terms:

Enterocolitis
Enterocolitis, Necrotizing
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases

Meropenem
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 24, 2012