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Efficacy, Pharmacokinetics and Safety of Meropenem in Infants Below 90 Days With Clinical or Confirmed Late-onset Sepsis (NeoMero-1)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2012 by PENTA Foundation
Sponsor:
Collaborator:
Chiesi Farmaceutici S.p.A.
Information provided by (Responsible Party):
PENTA Foundation
ClinicalTrials.gov Identifier:
NCT01551394
First received: February 27, 2012
Last updated: November 21, 2012
Last verified: November 2012
  Purpose

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.


Condition Intervention Phase
Sepsis
Drug: Meropenem
Drug: Ampicillin + gentamicin or cefotaxime + gentamicin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy, Pharmacokinetics and Safety of Meropenem in Infants Below 90 Days of Age (Inclusive) With Clinical or Confirmed Late-onset Sepsis : a European Multicenter Randomised Phase III Trial

Resource links provided by NLM:


Further study details as provided by PENTA Foundation:

Primary Outcome Measures:
  • percentage of patients with a favorable outcome in the two arms [ Time Frame: an expected average of 14 days ] [ Designated as safety issue: Yes ]

    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.


Secondary Outcome Measures:
  • Nature, frequency and numbers of clinical and biological adverse events [ Time Frame: 3 - 28 days ] [ Designated as safety issue: Yes ]
    Adverse events will also be summarised according to the need of a specific medical intervention or not. Analyses by time period will also be shown (from D0 to TOC visit and from TOC visit to follow-up). The number of patients experiencing at least one adverse event between D0 and TOC visit will be compared by treatment group.


Estimated Enrollment: 550
Study Start Date: September 2012
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Meropenem

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
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.
Other Name: Meropenem trihydrate
Active Comparator: Standard of care

The two accepted therapeutic options are:

  • ampicillin + gentamicin (SOC regimen 1) and
  • cefotaxime + gentamicin (SOC regimen 2).
Drug: Ampicillin + gentamicin or cefotaxime + gentamicin

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.

Other Names:
  • Ampicillin sodium
  • Gentamicin sulphate
  • Cefotaxime sodium

Detailed Description:

The principal objective is to compare the efficacy at test of cure (TOC) visit of meropenem to the standard of care (SOC) in the treatment of clinical or confirmed LOS in infants ≤ 90 days of postnatal age.

The secondary objectives are:

  • To compare the safety profile of meropenem to SOC
  • To compare the efficacy at TOC visit of meropenem to SOC in confirmed sepsis
  • To compare the response to meropenem and SOC on day 3 of antibacterial therapy
  • To compare the efficacy at TOC visit of meropenem to SOC ignoring the change of antibiotic(s) for safety reasons
  • To compare the efficacy at TOC visit of meropenem to SOC by SOC regimen
  • To compare survival at follow up (FU) visit (28 day visit) in the meropenem arm and SOC arm
  • To compare new infections and relapses that occur between TOC and FU visits in participants with a favourable outcome at TOC visit by treatment arm
  • To define the organisms causing LOS
  • To study antibacterial susceptibility of LOS-causing organisms and to describe clinical and microbiological responses according to this
  • To compare gut colonization by antibiotic resistant organisms after treatment with meropenem or SOC
  • To compare bacterial eradication by treatment arm
  • To compare time to NICU discharge across the 2 arms
  • To describe PK of meropenem in infants ≤ 90 days of postnatal age with LOS
  • To evaluate genetic parameters that may affect response to therapy
  Eligibility

Ages Eligible for Study:   up to 90 Days
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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:

    • white blood cells (WBC) count < 4 or > 20 x 109 cells/L,
    • immature to total neutrophil ratio (I/T) > 0.2,
    • platelet count < 100 x 109/L,
    • C-reactive protein (CRP) > 15 mg/L or procalcitonin ≥ 2 ng/mL,
    • glucose intolerance when receiving normal glucose amounts (8-15 g/kg/day) as expressed by blood glucose values > 180 mg/dL or hypoglycemia (< 40 mg/dL) confirmed at least two times,
    • acidosis as characterized by base excess (BE) < -10 mmol/L or lactate with value above 2 mmol/L.

confirmed sepsis is defined as positive culture for pathogens in a sample from a normally sterile site and at least one laboratory sign or clinical sign (from the list above)

  • For children above 44 weeks corrected age

clinical sepsis is defined according to the Goldstein criteria (Goldstein et al, 2005) as at least two of the following criteria, one of which must be abnormal temperature or WBC count:

  • Core temperature of > 38.5 °C or < 36 °C;
  • Tachycardia, defined as mean heart rate > to the 95th percentile for age group in the absence of external stimulus, chronic drugs, or painful stimuli or unexplained persistent elevation over a 0.5 to 4 hour time period; or bradycardia, defined as a mean heart rate < to the 5th percentile for age group in the absence of external vagal stimulus, beta blocker drugs, or congenital heart disease or unexplained persistent depression over a 0.5 hour time period;
  • Mean respiratory rate > to the 95th percentile for age group or mechanical ventilation for an acute process not related to underlying neuromuscular disease or the receipt of general anaesthesia;
  • Leukocyte count < the 5th percentile or > than the 95th percentile for age group (not secondary to chemotherapy-induced leucopoenia).

confirmed sepsis: positive culture for pathogens in a sample from a normally sterile site and at least one laboratory sign or clinical sign (from the list above)

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01551394

Locations
Italy
Ursula TRAFOJER Recruiting
Padova, Italy, 35128
Contact: Gianluca Visintin    + 39 0498213585    gianluca@visintin.com   
Principal Investigator: Ursula Trafojer         
Sponsors and Collaborators
PENTA Foundation
Chiesi Farmaceutici S.p.A.
Investigators
Principal Investigator: Ursula Trafojer Clinica Pediatrica, Padova
Principal Investigator: Irja Lutsar University of Tartu, Estonia
Study Chair: Jean-Pierre Aboulker Institut National de la Santé Et de la Recherche Médicale, France
  More Information

Additional Information:
No publications provided

Responsible Party: PENTA Foundation
ClinicalTrials.gov Identifier: NCT01551394     History of Changes
Other Study ID Numbers: 2011-001515-31
Study First Received: February 27, 2012
Last Updated: November 21, 2012
Health Authority: Italy: Ethics Committee
Estonia: Research Ethics Committee
Estonia: The State Agency of Medicine
Spain: Ethics Committee
Spain: Spanish Agency of Medicines
Lithuania: Bioethics Committee
Lithuania: State Medicine Control Agency - Ministry of Health
Greece: Ethics Committee
Greece: National Organization of Medicines

Keywords provided by PENTA Foundation:
sepsis
neonates
meropenem

Additional relevant MeSH terms:
Sepsis
Toxemia
Infection
Inflammation
Pathologic Processes
Systemic Inflammatory Response Syndrome
Ampicillin
Cefotaxime
Cefoxitin
Gentamicins
Meropenem
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Synthesis Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014