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

Necrotizing Enterocolitis Clinical Trial

Official title:

Multiple Dose Pharmacokinetic Study of Meropenem in Young Infants (<91 Days) With Suspected or Complicated Intra-abdominal Infections

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00621192
• Other study ID #: HHSN267200700051C
• Secondary ID: HHSN267200700051
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 2008
• Est. completion date: October 2009

Study information

• Verified date: March 2023
• Source: The Emmes Company, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 200
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 90 Days

Eligibility

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

Related Conditions & MeSH terms

• Communicable Diseases
• Enterocolitis
• Enterocolitis, Necrotizing
• Infections
• Intra-abdominal Infection
• Intraabdominal Infections
• Necrotizing Enterocolitis

Intervention

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

Locations

Country	Name	City	State
United States	Akron Children's Hospital	Akron	Ohio
United States	Albany Medical Center	Albany	New York
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Alabama	Birmingham	Alabama
United States	Suny Downstate Medical Center	Brooklyn	New York
United States	Case Western Reserve, RB&C, UHCMC	Cleveland	Ohio
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	Duke University Medical Center	Durham	North Carolina
United States	Evanston Northwestern Healthcare	Evanston	Illinois
United States	University of Florida	Gainesville	Florida
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Baylor College of Medicine	Houston	Texas
United States	Indiana University - Riley Hospital for Children	Indianapolis	Indiana
United States	Kansas City Children's Mercy Hospital	Kansas City	Missouri
United States	University of Louisville	Louisville	Kentucky
United States	Vanderbilt Children's Hospital	Nashville	Tennessee
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Children's Hospital of Oakland	Oakland	California
United States	Children's Hospital of Orange County	Orange	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Magee Women's Hospital	Pittsburgh	Pennsylvania
United States	University of Utah medical Center	Salt Lake City	Utah
United States	Sharp-Mary Birch Hospital for Women	San Diego	California
United States	University of California Medical Center	San Diego	California
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
The Emmes Company, LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	Deaths		Up to 51 days (Recorded from the time of informed consent until 72 hours following the last dose of study drug)
Primary	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
Primary	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)