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

Primary Purpose

Necrotizing Enterocolitis, Intra-abdominal Infection

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
meropenem
Sponsored by
The Emmes Company, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Necrotizing Enterocolitis focused on measuring meropenem, infants, intra-abdominal infection, pharmacokinetics, safety

Eligibility Criteria

undefined - 90 Days (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama
  • Children's Hospital of Oakland
  • Children's Hospital of Orange County
  • University of California Medical Center
  • Sharp-Mary Birch Hospital for Women
  • Yale New Haven Hospital
  • Children's National Medical Center
  • University of Florida
  • Kapiolani Medical Center for Women and Children
  • Evanston Northwestern Healthcare
  • Indiana University - Riley Hospital for Children
  • University of Louisville
  • University of Michigan
  • Kansas City Children's Mercy Hospital
  • Albany Medical Center
  • Suny Downstate Medical Center
  • Duke University Medical Center
  • Duke University
  • Akron Children's Hospital
  • Case Western Reserve, RB&C, UHCMC
  • Children's Hospital of Philadelphia
  • Magee Women's Hospital
  • Vanderbilt Children's Hospital
  • University of Texas Southwestern Medical Center
  • Baylor College of Medicine
  • University of Utah medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Meropenem

Arm Description

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.

Outcomes

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)
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
Meropenem Clearance
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
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

Secondary Outcome Measures

Full Information

First Posted
February 20, 2008
Last Updated
March 30, 2023
Sponsor
The Emmes Company, LLC
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1. Study Identification

Unique Protocol Identification Number
NCT00621192
Brief Title
Pharmacokinetic (PK) and Safety Study of Meropenem in Young Infants With Intra-abdominal Infections
Official Title
Multiple Dose Pharmacokinetic Study of Meropenem in Young Infants (<91 Days) With Suspected or Complicated Intra-abdominal Infections
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
June 2008 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
October 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Emmes Company, LLC

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Necrotizing Enterocolitis, Intra-abdominal Infection
Keywords
meropenem, infants, intra-abdominal infection, pharmacokinetics, safety

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
200 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Meropenem
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
meropenem
Other Intervention Name(s)
Merrem
Intervention Description
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
Primary Outcome Measure Information:
Title
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)
Description
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.
Time Frame
Average of 12 days (3 to 21 days)
Title
Deaths
Time Frame
Up to 51 days (Recorded from the time of informed consent until 72 hours following the last dose of study drug)
Title
Meropenem Clearance
Description
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.
Time Frame
Up to 7-8hrs post drug administration
Title
Key Safety Endpoints
Description
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
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)

10. Eligibility

Sex
All
Maximum Age & Unit of Time
90 Days
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Danny Benjamin, MD, PhD, MPH
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Alabama
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Children's Hospital of Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
University of California Medical Center
City
San Diego
State/Province
California
ZIP/Postal Code
92117
Country
United States
Facility Name
Sharp-Mary Birch Hospital for Women
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Yale New Haven Hospital
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
Kapiolani Medical Center for Women and Children
City
Honolulu
State/Province
Hawaii
ZIP/Postal Code
96826
Country
United States
Facility Name
Evanston Northwestern Healthcare
City
Evanston
State/Province
Illinois
ZIP/Postal Code
60056
Country
United States
Facility Name
Indiana University - Riley Hospital for Children
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
Kansas City Children's Mercy Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Facility Name
Albany Medical Center
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Suny Downstate Medical Center
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11203
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27708
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27715
Country
United States
Facility Name
Akron Children's Hospital
City
Akron
State/Province
Ohio
ZIP/Postal Code
44308
Country
United States
Facility Name
Case Western Reserve, RB&C, UHCMC
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Magee Women's Hospital
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Vanderbilt Children's Hospital
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah medical Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84108
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22955430
Citation
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.
Results Reference
derived

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

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