SepsisPhase 3NeoMero-1NCT01551394
Efficacy, Pharmacokinetics and Safety of Meropenem in Infants Below 90 Days With Clinical or Confirmed Late-onset Sepsis
A Phase 3 study testing Meropenem and Ampicillin + gentamicin or cefotaxime + gentamicin in people with Sepsis, run by PENTA Foundation at 1 site in Italy.
Trial 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). Read more about this study
- Who is it for?
- Ages 72 hours to 90 days
- Conditions the study is for
- Sepsis
- What is being tested?
- Meropenem and Ampicillin + gentamicin or cefotaxime + gentamicin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 272 participants
- Where
- 1 siteItaly
- Study dates
- Sep 2012to Dec 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 72 hours to 90 days
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
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- 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)
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Conditions
- Sepsis
- Being tested
- Meropenem, Ampicillin + gentamicin or cefotaxime + gentamicin
- Keywords
- sepsis, neonates, meropenem
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MeropenemDrug
Also called Meropenem trihydrate
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.
Ampicillin + gentamicin or cefotaxime + gentamicinDrug
Also called Ampicillin sodium, Gentamicin sulphate, Cefotaxime sodium
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Meropenem |
| Standard of care | Active comparator | The two accepted therapeutic options are:
* ampicillin + gentamicin (SOC regimen 1) and
* cefotaxime + gentamicin (SOC regimen 2). Receives: Drug: Ampicillin + gentamicin or cefotaxime + gentamicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: an expected average of 14 days
Secondary outcomes (1)
Nature, frequency and numbers of clinical and biological adverse events
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.
Measured: 3 - 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Mar 2012 (estimated)
- Study startSep 2012
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SepsisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 272 participants (actual)
Sponsor and investigators
- Lead sponsor
- PENTA Foundation
- Sponsor type
- Research network
- Collaborators
- Chiesi Farmaceutici S.p.A.
- Responsible party
- Sponsor
- Investigators
- Ursula Trafojer, Principal investigator, Clinica Pediatrica, PadovaIrja Lutsar, Principal investigator, University of Tartu, EstoniaJean-Pierre Aboulker, Study chair, Institut National de la Santé Et de la Recherche Médicale, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01551394
- Sponsor's protocol ID
- 2011-001515-31
- Acronym
- NeoMero-1
- Status last verified
- Feb 2015
- First submitted
- 27 Feb 2012
- Last updated
- 16 Feb 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01551394
- Acronym / sponsor ID
- NeoMero-1 / 2011-001515-31
- Conditions
- Sepsis
- Keywords
- sepsis, neonates, meropenem
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 272 participants (actual)
- Lead sponsor
- PENTA FoundationResearch network
- Collaborators
- Chiesi Farmaceutici S.p.A.
- Study start
- Sep 2012
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 12 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Meropenem | Experimental | Drug: MeropenemInfants 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. |
| Standard of care | Active comparator | Drug: Ampicillin + gentamicin or cefotaxime + gentamicinThe two accepted therapeutic options are: * ampicillin + gentamicin (SOC regimen 1) and * cefotaxime + gentamicin (SOC regimen 2). |
Who may qualify
- Ages
- 72 hours to 90 days
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (29 listed)
- 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
- 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
Key exclusion criteria (7 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MeropenemAlso: Meropenem trihydrate20 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 |
| Ampicillin + gentamicin or cefotaxime + gentamicinAlso: Ampicillin sodium, Gentamicin sulphate, Cefotaxime sodiumAmpicillin: 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. | Drug | Standard of care |
Primary outcome
percentage of patients with a favorable outcome in the two arms
Time frame: an expected average of 14 days
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.
1 secondary outcome
Nature, frequency and numbers of clinical and biological adverse events
Time frame: 3 - 28 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2015.
- Site dedicated to the NeoMero studiesLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ursula Trafojer principal investigator
Clinica Pediatrica, Padova
Irja Lutsar principal investigator
University of Tartu, Estonia
Jean-Pierre Aboulker study chair
Institut National de la Santé Et de la Recherche Médicale, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Meropenem and Ampicillin + gentamicin or cefotaxime + gentamicin in people with Sepsis, run by PENTA Foundation at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 29 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
percentage of patients with a favorable outcome in the two arms (time frame: an expected average of 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Feb 2015.