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

Phase 1

Completed

• Conditions: Intra-abdominal Infection; Necrotizing Enterocolitis
• Interventions: Drug: meropenem

• Registration Number: NCT00621192
• Lead Sponsor: The Emmes Company, LLC

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:

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.

Study Timeline

• Study First Submitted: 2008-02-20
• Study First Submitted QC: 2008-02-20
• Study First Posted: 2008-02-22
• Study Start: 2008-06
• Primary Completion: 2009-10
• Study Completion: 2009-10
• Results First Submitted: 2011-10-20
• Results First Submitted QC: 2011-10-20
• Results First Posted: 2011-11-29
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-30
• Last Update Posted: 2023-04-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 200

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Meropenem	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.

Primary Outcome Measures

Name	Time	Method
Deaths	Up to 51 days (Recorded from the time of informed consent until 72 hours following the last dose of study drug)
Key Safety Endpoints	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
Meropenem Clearance	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.
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)	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.

Trial Locations

Locations (26)

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Magee Women's Hospital; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Texas Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

University of California Medical Center; 🇺🇸 San Diego, California, United States

Sharp-Mary Birch Hospital for Women; 🇺🇸 San Diego, California, United States

Indiana University - Riley Hospital for Children; 🇺🇸 Indianapolis, Indiana, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Duke University; 🇺🇸 Durham, North Carolina, United States

Baylor College of Medicine; 🇺🇸 Houston, Texas, United States

Children's Hospital of Orange County; 🇺🇸 Orange, California, United States

Kapiolani Medical Center for Women and Children; 🇺🇸 Honolulu, Hawaii, United States

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

Vanderbilt Children's Hospital; 🇺🇸 Nashville, Tennessee, United States

University of Utah medical Center; 🇺🇸 Salt Lake City, Utah, United States

Children's Hospital of Oakland; 🇺🇸 Oakland, California, United States

Evanston Northwestern Healthcare; 🇺🇸 Evanston, Illinois, United States

Albany Medical Center; 🇺🇸 Albany, New York, United States

Case Western Reserve, RB&C, UHCMC; 🇺🇸 Cleveland, Ohio, United States

Akron Children's Hospital; 🇺🇸 Akron, Ohio, United States

Suny Downstate Medical Center; 🇺🇸 Brooklyn, New York, United States

Yale New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States

University of Louisville; 🇺🇸 Louisville, Kentucky, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Kansas City Children's Mercy Hospital; 🇺🇸 Kansas City, Missouri, United States