Bolus Versus Prolonged Infusion of Meropenem in Newborn With Late Onset Sepsis (BVPIMNBLOS)

Bolus Versus Prolonged Infusion of Meropenem in Newborn With Late Onset Sepsis: A Randomized Control Trial

Newborns in the neonatal intensive care unit (NICU), especially premature ones with immature organ systems, frequently suffer nosocomial infections caused by microorganisms resistant to narrow-spectrum antibiotics like ampicillin and gentamicin and require introduction of new agents with a wider spectrum of activity.

Meropenem has activity against wide variety of Gram-negative and Gram-positive bacteria. It is well tolerated by children and neonates, including preterm babies, and allowing monotherapy instead of combined therapy.

Severe neonatal infections with increasing antibiotic resistance are major problems affecting morbidity and mortality in the NICU. Few number of new antibacterial agents entering the clinic and new agents for multi-drug resistant Gram-negative bacteria will unlikely be available in the near future.

Study Overview

• Status: Completed
• Conditions: Late Onset Neonatal Sepsis
• Intervention / Treatment: Drug: Meropenem.

Detailed Description

More research into existing antibiotics with novel mechanisms of action are required to combat the increased resistance and decreased development of antibiotics. Efforts were exerted to maximize antibiotic efficacy by optimal dosing based on pharmacodynamic and pharmacokinetic properties of antibiotics.

Meropenem is administered mostly via a 30-min infusion, as some data indicate rapid degradation after reconstitution. Dose recommendations from two pediatric studies using Monte Carlo simulation have emphasized that a 4-h infusion may be needed if microorganisms showed increased minimal inhibitory concentrations (MICs), more specifically, for Pseudomonas aeruginosa. A prolonged-infusion strategy has not been tested in neonates, although some data suggest that extremely small infusion volumes may significantly affect the drug amount actually delivered.

Aim of work:

The objective of our study is to compare the clinical and bacteriological efficacy of conventional intermittent dosing of meropenem to the prolonged infusions in critically-ill neonates, with a proactive focus on reducing ventilator days in ventilated patients, length of stay in NICU, and neonatal mortality.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 days to 4 weeks (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Neonates admitted to the neonatal care unit (NCU) who suffer from late onset sepsis (LOS) at admission or during their NICU stay and receive meropenem for at least four days

Exclusion Criteria:

• Acute or chronic renal failure
• Hypersensitivity or allergy to meropenem

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Infusion arm; Infants will receive a loading dose of 20 mg/kg/dose every 8 hours for sepsis and 40 mg/kg/dose every 8 hours in meningitis and pseudomonas infection. Each dose will be infused over four hours.	Drug: Meropenem.; Infants in both groups will receive a loading dose of 20 mg/kg/dose every 8 hours for sepsis and 40 mg/kg/dose every 8 hours in meningitis and pseudomonas infection
Active Comparator: Bolus group; Infants will receive a loading dose of 20 mg/kg/dose every 8 hours for sepsis and 40 mg/kg/dose every 8 hours in meningitis and pseudomonas infection. Each dose will be infused over thirty minutes.	Drug: Meropenem.; Infants in both groups will receive a loading dose of 20 mg/kg/dose every 8 hours for sepsis and 40 mg/kg/dose every 8 hours in meningitis and pseudomonas infection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical outcome	Success is defined as complete or partial resolution of leukocytosis, temperature, and clinical signs and symptoms of infection.; Failure consists of persistence or progression of signs and symptoms of infection, development of new clinical findings consistent with active infection, or death from infection.	15-28 days from Meropenem treatment
Microbiological outcome	Success is defined as eradication of infection or colonization which means detection of a new pathogen from the site of infection during meropenem therapy and no new antibiotic is indicated; Failure is defined as persistence of infection and superinfection which means detection of a new pathogen from the site of infection during meropenem therapy and new antibiotic is indicated.	7-21 days from Meropenem treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Meropenem-related length of mechanical ventilation	The number of mechanical ventilation days from the start of meropenem administration	0-31 days from Meropenem treatment
Meropenem-related length of NICU stay	The number of days from the beginning of meropenem therapy to discharge from NICU	10 weeks from Meropenem treatment
NICU mortality	Death before discharge	12 weeks from time of admission
Duration of meropenem treatment	Total days of meropenem treatment	3-28 days
Clinical side effects of meropenem treatment	Safety of meropenem therapy will be evaluated by clinical symptoms (diarrhea, rash, vomiting and seizures).	3-28 days from meropenem treatment
Laboratory derangement related to meropenem treatment	Assessment of laboratory parameters and their changes during meropenem therapy (transaminases, alkaline phosphatase, bilirubin).	3-28 days from meropenem treatment

Collaborators and Investigators

• Sponsor: Mansoura University

Publications and helpful links

General Publications

• Shabaan AE, Nour I, Elsayed Eldegla H, Nasef N, Shouman B, Abdel-Hady H. Conventional Versus Prolonged Infusion of Meropenem in Neonates With Gram-negative Late-onset Sepsis: A Randomized Controlled Trial. Pediatr Infect Dis J. 2017 Apr;36(4):358-363. doi: 10.1097/INF.0000000000001445.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: June 9, 2015
• First Submitted That Met QC Criteria: July 17, 2015
• First Posted (Estimate): July 21, 2015

Study Record Updates

• Last Update Posted (Estimate): July 21, 2015
• Last Update Submitted That Met QC Criteria: July 17, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: meropenem; newborn; infusion; management; late-onset sepsis
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Infant, Newborn, Diseases; Sepsis; Toxemia; Neonatal Sepsis; Anti-Infective Agents; Anti-Bacterial Agents; Meropenem
• Other Study ID Numbers: 67890