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

NCT00621192 | Completed Phase 1 Results DMC

• 1 other identifier: HHSN267200700051C
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 26

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.

Conditions

Necrotizing Enterocolitis; Intra-abdominal Infection

Keywords

meropenem; infants; intra-abdominal infection; pharmacokinetics; safety

Outcome Measures

Primary Outcomes (4)

• 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.

  Average of 12 days (3 to 21 days)

• Deaths

  Up to 51 days (Recorded from the time of informed consent until 72 hours following the last dose of study drug)

• 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.

  Up to 7-8hrs post drug administration

• 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

  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)

Study Arms (1)

Meropenem

EXPERIMENTAL

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.

Drug: meropenem

Interventions

meropenem DRUG

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

Also known as: Merrem

Meropenem

Eligibility Criteria

• Age: Up to 90 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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
• \) 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The Emmes Company, LLC: lead

Study Sites (26)

University of Alabama

Birmingham, Alabama, 35233, United States

Location

Children's Hospital of Oakland

Oakland, California, 94609, United States

Location

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

University of California Medical Center

San Diego, California, 92117, United States

Location

Sharp-Mary Birch Hospital for Women

San Diego, California, 92123, United States

Location

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States

Location

Evanston Northwestern Healthcare

Evanston, Illinois, 60056, United States

Location

Indiana University - Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

University of Louisville

Louisville, Kentucky, 40202, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

Kansas City Children's Mercy Hospital

Kansas City, Missouri, 64108, United States

Location

Albany Medical Center

Albany, New York, 12208, United States

Location

Suny Downstate Medical Center

Brooklyn, New York, 11203, United States

Location

Duke University Medical Center

Durham, North Carolina, 27708, United States

Location

Duke University

Durham, North Carolina, 27715, United States

Location

Akron Children's Hospital

Akron, Ohio, 44308, United States

Location

Case Western Reserve, RB&C, UHCMC

Cleveland, Ohio, 44106, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Magee Women's Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt Children's Hospital

Nashville, Tennessee, 37232, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

University of Utah medical Center

Salt Lake City, Utah, 84108, United States

Location

Related Publications (1)

• 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.

  PMID: 22955430 DERIVED

MeSH Terms

Conditions

Enterocolitis, Necrotizing; Intraabdominal Infections

Interventions

Meropenem

Condition Hierarchy (Ancestors)

Enterocolitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Infections

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: David Siegel, MD
• Organization: Eunice Kennedy Shriver National Institute of Child Health and Human Development

siegelda@mail.nih.gov

301-595-8670

Study Officials

• Danny Benjamin, MD, PhD, MPH

  Duke University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2008
• First Posted: February 22, 2008
• Study Start: June 1, 2008
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: April 25, 2023
• Results First Posted: November 29, 2011

Record last verified: 2023-03

Locations

US (26)