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Neonatal Vancomycin Trial (NeoVanc)

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ClinicalTrials.gov Identifier: NCT02790996
Recruitment Status : Recruiting
First Posted : June 6, 2016
Last Update Posted : June 29, 2018
Sponsor:
Collaborators:
St George's, University of London
Institut National de la Santé Et de la Recherche Médicale, France
University of Tartu
Consorzio per Valutazioni Biologiche e Farmacologiche
University of Liverpool
Therakind limited
Bambino Gesù Hospital and Research Institute
Servicio Madrileño de Salud, Madrid, Spain
Aristotle University Of Thessaloniki
University of Edinburgh
SYNAPSE Research Management Partners S.L
European Commission
Information provided by (Responsible Party):
PENTA Foundation

Brief Summary:
The study aims to compare the efficacy, safety and pharmacokinetics (PK) of an optimised dosing to a standard dosing regimen of vancomycin in neonates and infants aged ≤ 90 days with late onset bacterial sepsis known or suspected to be caused by Gram-positive microorganisms

Condition or disease Intervention/treatment Phase
Late Onset Neonatal Sepsis Drug: Vancomycin Phase 2

Detailed Description:

Detailed objectives of the study are:

  • To compare the efficacy of an optimised vancomycin dosing regimen to a standard vancomycin dosing regimen in patients with late onset, bacterial sepsis, known or suspected to be caused by Gram-positive microorganisms.
  • To compare the safety of vancomycin (including renal and hearing safety) by allocation group in the intention to treat (ITT) population
  • To describe the PK parameters according to vancomycin dosing regimen and outcome using population PK modelling in the ITT population
  • To describe PK/PD in terms of the probability of target attainment (PTA) with different vancomycin dosing regimens in the ITT and per protocol (PP) populations
  • To describe outcomes and duration of therapy at the end of vancomycin treatment and at the short term follow-up visit by allocation group in the ITT and PP populations
  • To compare the clinical outcome to the antibacterial susceptibility of infecting organisms
  • To compare colonisation by resistant microorganisms (e.g. vancomycin-resistant enterococci (VRE)) and Candida spp. by allocation group at baseline, TOC and short-term follow-up
  • To validate across multiple centres a host biomarker panel to allow improved diagnosis of bacterial sepsis and monitor response to antibacterial therapy

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multi-centre, Randomised, Open Label, Phase IIb Study to Compare the Efficacy, Safety and Pharmacokinetics (PK) of an Optimised Dosing to a Standard Dosing Regimen of Vancomycin in Neonates and Infants Aged ≤ 90 Days With Late Onset Bacterial Sepsis Known or Suspected to be Caused by Gram-positive Microorganisms
Actual Study Start Date : February 27, 2017
Estimated Primary Completion Date : December 1, 2018
Estimated Study Completion Date : February 1, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sepsis

Arm Intervention/treatment
Experimental: Vancomycin - Optimised Regimen

A single loading dose of 25 mg/kg followed by a maintenance dose of:

Postmenstrual age ≤ 35 weeks - 15 mg/kg 12 hourly; Postmenstrual age > 35 weeks - 15 mg/kg 8 hourly

Drug: Vancomycin
Vancomycin is an antibiotic used to treat a number of bacterial infections.It is recommended intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by methicillin-resistant S. aureus.

Active Comparator: Vancomycin - Standard Regimen
Postmenstrual age < 29 weeks - 15 mg/kg given 24 hourly; Postmenstrual age 29 - 35 weeks - 15 mg/kg 12 hourly; Postmenstrual age > 35 weeks - 15 mg/kg 8 hourly
Drug: Vancomycin
Vancomycin is an antibiotic used to treat a number of bacterial infections.It is recommended intravenously as a treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by methicillin-resistant S. aureus.




Primary Outcome Measures :
  1. Successful outcome at Test of Cure visit [ Time Frame: 10±1 days after End of Actual Vancomycin Therapy ]
    Patient is alive AND has a successful outcome at the end of actual vancomycin therapy AND the patient has not had a clinically or microbiologically significant relapse or new infection.


Secondary Outcome Measures :
  1. Clinically or microbiologically significant relapse or new infection requiring treatment with any other antibiotic for more than 24 hours [ Time Frame: 10±1 days after the End of Actual Vancomycin Treatment ]
  2. Successful outcome at Visit 4 or End of Actual Vancomycin Therapy including total duration of vancomycin therapy [ Time Frame: Day 5±1 or Day 10±2 ]
  3. Abnormal renal function tests at the Short-term Follow-Up Visit [ Time Frame: 30±5 days post-initiation of vancomycin therapy ]
  4. Abnormal hearing screening test [ Time Frame: By Day 90 post-initiation of vancomycin therapy ]
  5. Comparative safety of vancomycin (relating to the number of treatment-related adverse events other than those associated with renal function and hearing) at Short Term Follow-Up Visit [ Time Frame: 30±5 days post-initiation of vancomycin therapy ]
  6. Pharmacokinetic parameters of vancomycin using population PK modelling by allocation group [ Time Frame: Up to 2 years (final data collection date for outcome measure) ]
    Area under the plasma concentration time curve - AUC (mg*hour/L)

  7. Probability of target attainment (PTA) with different study regimens [ Time Frame: Up to 2 years (final data collection date for outcome measure) ]
    Different bacteriological targets will be tested, based on the MIC of different bacteria of interest with level of sensitivity. Simulations based on the vancomycin popPK model will be conducted to define the number of patients in the different allocation groups reaching the predefined targets when modifying the dose.

  8. Relationship between CoNS species and duration of treatment and CRP response [ Time Frame: Day 5±1 or Day 10±1 ]
  9. Gut colonisation by vancomycin resistant organisms at baseline, Test of Cure Visit and Short-term Follow-Up Visit [ Time Frame: Baseline, 10±1 days after end of vancomycin therapy, 30±5 days post-initiation of vancomycin therapy ]
  10. Skin colonisation and resistance patterns before and after vancomycin treatment [ Time Frame: Baseline, 10±1 days after end of vancomycin therapy, 30±5 days post-initiation of vancomycin therapy ]
  11. Assessment of changes in host biomarker panel profiles from baseline to End of Actual Vancomycin Therapy and the relationship between host biomarker and duration of treatment [ Time Frame: Day 3 and Day 5±1, Day 10±1 (standard arm only) ]
    Functional molecular units based on a multimarker panel - a set of 52 biomarkers will be performed as a classifier with high accuracy and specificity in predicting bacterial infection



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 90 Days   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Postnatal age ≤ 90 days AND
  • Postnatal age ≥ 72 hours at onset of sepsis AND
  • Clinical sepsis as defined by presence of any three clinical or laboratory criteria from the list below OR
  • Confirmed, significant bacterial sepsis as defined by positive culture with a Gram-positive bacterium from a normally sterile site and at least one clinical or one laboratory criterion from the list below, in the 24 hours before randomisation

Clinical criteria

  • hyper- or hypothermia,
  • hypotension or impaired peripheral perfusion or mottled skin,
  • apnoea or increased oxygen requirement or increased requirement for ventilatory support,
  • bradycardic episodes or tachycardia,
  • worsening feeding intolerance or abdominal distension,
  • lethargy or hypotonia or irritability

Laboratory criteria:

  • white blood cell (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) > 10 mg/L
  • glucose intolerance as defined by a blood glucose value > 180 mg/dL (> 10 mmol/L) when receiving normal glucose amounts (8 - 15 g/kg/day)
  • metabolic acidosis as defined by a base excess (BE) < -10 mmol/L (-10 mEq/L) or a blood lactate value > 2 mmol/L

Exclusion Criteria:

  • Administration of any systemic antibiotic regimen for more than 24 hours prior to randomisation, unless the change is driven by the apparent lack of efficacy of the original regimen
  • Treatment with vancomycin for ≥ 24 hours at any time within 7 days of enrolment
  • Known toxicity, hypersensitivity or intolerance to vancomycin
  • Known renal impairment with urinary output < 0.7 ml/kg/hour for 24 hours or a creatinine value ≥ 100 µmol/L (1.13 mg/dL)
  • Patient receiving (or planned to receive) haemofiltration, haemodialysis, peritoneal dialysis, extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass
  • Severe congenital malformations where the infant is not expected to survive for more than 3 months
  • Patient known to have S. aureus (MSSA or MRSA) bacteraemia
  • Patient with osteomyelitis, septic arthritis, urinary tract infection (UTI) or meningitis
  • Patient with high suspicion of/confirmed sepsis caused by Gram-negative organisms or fungi
  • Other situations where the treating physician considers a different empiric antibiotic regimen necessary
  • Current participation in any other clinical study of an investigational medicinal product (IMP)

Post-randomisation exclusions

• Any participant found to have Gram-negative or fungal sepsis, osteomyelitis, septic arthritis, UTI, meningitis or S. aureus (MSSA or MRSA) bacteraemia after randomisation will be excluded from analysis. Participants who have received at least one dose of study vancomycin will be followed up for safety


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02790996


Contacts
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Contact: Louise Hill, MBChB MRCPCH 0208 725 4851 ext 4851 lhill@sgul.ac.uk

Locations
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Estonia
Tallinn's Children's Hospital Recruiting
Tallinn, Estonia
Contact: Mari-Liis Ilmoja         
Paediatric Intensive Care Unit, Clinicum of the University of Tartu Recruiting
Tartu, Estonia
Contact: Tuuli Metsvaht         
Greece
Aghia Sophia Children's Hospital (A) Recruiting
Athens, Greece
Contact: Korina Karachristou         
Aghia Sophia Children's Hospital (B) Recruiting
Athens, Greece
Contact: Fani Anatolitou         
Aghia Sophia Children's Hospital (C) Not yet recruiting
Athens, Greece
Contact: Tania Siahanidou         
Kyriakou Children's Hospital Recruiting
Athens, Greece
Contact: Angeliki Nika         
General University Hospital Attikon Not yet recruiting
Chaïdári, Greece
Contact: Vana Papaevangelou         
Hippokration Hospital - Department of Neonatology Recruiting
Thessaloniki, Greece
Contact: Kosmas Sarafidis         
Papageorgiou 2nd Department of Neonatology Recruiting
Thessaloniki, Greece
Contact: George Mitsiakos         
Italy
Ospedale "Di Venere" - Carbonara di Bari Not yet recruiting
Bari, Italy
Contact: Antonio Del Vecchio         
ASST Grande Ospedale Metropolitano Niguarda Recruiting
Milan, Italy
Contact: Stefano Martinelli         
Azienda Ospedaliera di Padova Recruiting
Padova, Italy
Contact: Eugenio Baraldi         
Azienda Ospedaliera Universitaria Policlinico "P. Giaccone" Recruiting
Palermo, Italy
Contact: Mario Giuffrè         
Policlinico San Matteo Recruiting
Pavia, Italy
Contact: Mauro Stronati         
Ospedale Pediatrico Bambino Gesu' Recruiting
Rome, Italy
Contact: Andrea Dotta         
Ospedale Ostetrico Ginecologico Sant'Anna Recruiting
Turin, Italy
Contact: Paolo Manzoni         
Spain
Hospital Sant Joan de Deu Recruiting
Barcelona, Spain
Contact: Ana Alarcon, MD         
Hospital 12 de Octubre Recruiting
Madrid, Spain
Contact: Concha de Alba         
Hospital Materno Infantil, La Paz Recruiting
Madrid, Spain
Contact: Laura Sanchez         
United Kingdom
Royal Jubilee Maternity Hospital Recruiting
Belfast, United Kingdom
Contact: Paul Moriarty         
St Mary's Hospital Recruiting
Manchester, United Kingdom
Contact: Ajit Mahaveer         
John Radcliffe Hospital Recruiting
Oxford, United Kingdom
Contact: Charles Roehr         
Sponsors and Collaborators
PENTA Foundation
St George's, University of London
Institut National de la Santé Et de la Recherche Médicale, France
University of Tartu
Consorzio per Valutazioni Biologiche e Farmacologiche
University of Liverpool
Therakind limited
Bambino Gesù Hospital and Research Institute
Servicio Madrileño de Salud, Madrid, Spain
Aristotle University Of Thessaloniki
University of Edinburgh
SYNAPSE Research Management Partners S.L
European Commission
Investigators
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Study Chair: Mike Sharland, MD, FRCPCH St George's, University of London

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Responsible Party: PENTA Foundation
ClinicalTrials.gov Identifier: NCT02790996     History of Changes
Other Study ID Numbers: NeoVanc
First Posted: June 6, 2016    Key Record Dates
Last Update Posted: June 29, 2018
Last Verified: June 2018

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by PENTA Foundation:
sepsis
neonate
vancomycin
Additional relevant MeSH terms:
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Sepsis
Neonatal Sepsis
Infection
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Infant, Newborn, Diseases
Vancomycin
Anti-Bacterial Agents
Anti-Infective Agents