Efficacy, Pharmacokinetics and Safety of Meropenem in Infants Below 90 Days With Clinical or Confirmed Late-onset Sepsis

NCT01551394 | Completed Phase 3 DMC

• 1 other identifier: 2011-001515-31
• Study Type: interventional
• Target: 272
• Locations: 1 country
• Sites: 1

Brief Summary

This phase III multicentric international randomized trial is designed to compare the efficacy of Meropenem to the standard of care in infants below 90 days of age with clinical or confirmed late-onset sepsis (LOS). The aim is to assess efficacy , pharmacokinetics and safety of Meropenem which are not well known and documented in this population.

Conditions

Sepsis

Keywords

sepsis; neonates; meropenem

Outcome Measures

Primary Outcomes (1)

• percentage of patients with a favorable outcome in the two arms

  The proportions of participants with a favourable outcome will be calculated in the meropenem arm and in the SOC arm. A favourable outcome is met when an infant: * Is alive * Has resolution or significant improvement of all abnormalities that defined LOS at entry and has no new clinical or laboratory abnormalities requiring a new course of antibiotic therapy * Has microbiological eradication either confirmed or presumed and no new pathogens identified.

  an expected average of 14 days

Secondary Outcomes (1)

• Nature, frequency and numbers of clinical and biological adverse events

  3 - 28 days

Study Arms (2)

Meropenem

EXPERIMENTAL

Infants will received the Meropenem 20 mg/kg every 8 hours (every 12 hours in the youngest age group: \< 32 weeks GA and \< 2 weeks postnatal age). The dose will be given as an infusion over 30 minutes. Treatment duration is 11 ± 3 days.

Drug: Meropenem

Standard of care

ACTIVE COMPARATOR

The two accepted therapeutic options are: * ampicillin + gentamicin (SOC regimen 1) and * cefotaxime + gentamicin (SOC regimen 2).

Drug: Ampicillin + gentamicin or cefotaxime + gentamicin

Interventions

Meropenem DRUG

20 mg/kg every 8 hours (every 12 hours in the youngest age group: \< 32 weeks GA and \< 2 weeks postnatal age). The dose will be given as an infusion over 30 minutes. Treatment duration is 11 ± 3 days.

Also known as: Meropenem trihydrate

Meropenem

Ampicillin + gentamicin or cefotaxime + gentamicin DRUG

Ampicillin: Neonates below 7 days: 50mg/kg every 12 hours Neonates 7-21 days: 50mg/kg every 8 hours Neonates and Infants from day 22 on: 50mg/kg every 6 hours Gentamicin: Neonates less than 32 weeks of corrected age: 5mg/kg every 36 hours Neonates 32 weeks and over of corrected age: 5mg/kg every 24 hours (pre-dose ('trough') concentrations should be less than 2mg/l) Infants over 28 days of postnatal age: once daily dose: initially 5-7mg/kg, then adjust according to serum-gentamicin concentration (pre-dose ('trough') concentrations should be less than 1mg/l) Cefotaxime: Neonates below 7 days of PNA: 50mg/kg every 12 hours Neonates and infants from day 7 of PNA: 50mg/kg every 8 hours Treatment duration is 11 ± 3 days.

Also known as: Ampicillin sodium, Gentamicin sulphate, Cefotaxime sodium

Standard of care

Eligibility Criteria

• Age: 72 Hours - 90 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Informed consent form signed by the parents/carers
• Chronological age below 90 days inclusive
• Chronological age greater or equal to 72 hours of life at beginning of LOS
• Clinical or confirmed sepsis
• For infants below 44 weeks inclusive of corrected age
• clinical sepsis is defined, according to the Expert Meeting on Neonatal and Paediatric Sepsis (Report on the Expert Meeting on Neonatal and Paediatric Sepsis - 8 June 2010, EMA London), as the presence in the last 24 hours of at least
• two clinical criteria:
• hyper- or hypothermia or temperature instability,
• reduced urinary output or hypotension or mottled skin or impaired peripheral perfusion
• apnea or increased oxygen requirement or increased requirement for ventilatory support,
• bradycardia spells or tachycardia or rhythm instability,
• feeding intolerance or abdominal distension,
• lethargy or hypotonia or irritability,
• skin and subcutaneous lesions such as petechial rash or sclerema,
• and two laboratory criteria:

You may not qualify if:

• Administration of any systemic antibiotics for more than 24 hours prior to the randomisation, unless the change is driven by the lack of efficacy of the former regimen;
• Severe congenital malformations if the infant is not expected to survive for more than 3 months;
• Other situations where the treating physician considers a different antibiotic regimen necessary;
• Known intolerance or contraindication to study medication;
• Participation in any other clinical study of investigational drugs;
• Renal failure (as defined by Akcan-Arikan et al., 2007) and requirement of haemofiltration or peritoneal dialysis;
• Confirmed sepsis with microorganisms known to be resistant to study therapies.

Sponsors & Collaborators

• PENTA Foundation: lead
• Chiesi Farmaceutici S.p.A.: collaborator

Study Sites (1)

Ursula TRAFOJER

Padua, 35128, Italy

Location

Related Links

• Site dedicated to the NeoMero studies

MeSH Terms

Conditions

Sepsis

Interventions

Meropenem; Ampicillin; Gentamicins; Cefotaxime

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Penicillin G; Penicillins; Sulfur Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cephacetrile; Cephalosporins; Thiazines

Study Officials

• Ursula Trafojer

  Clinica Pediatrica, Padova

  PRINCIPAL INVESTIGATOR

• Irja Lutsar

  University of Tartu, Estonia

  PRINCIPAL INVESTIGATOR

• Jean-Pierre Aboulker

  Institut National de la Santé Et de la Recherche Médicale, France

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2012
• First Posted: March 12, 2012
• Study Start: September 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: February 16, 2015

Record last verified: 2015-02

Locations

IT (1)