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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

Tracking Information
First Submitted Date  ICMJE April 7, 2016
First Posted Date  ICMJE June 6, 2016
Last Update Posted Date June 29, 2018
Actual Study Start Date  ICMJE February 27, 2017
Estimated Primary Completion Date December 1, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 31, 2016)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02790996 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 31, 2016)
  • 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 ]
  • 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 ]
  • Abnormal renal function tests at the Short-term Follow-Up Visit [ Time Frame: 30±5 days post-initiation of vancomycin therapy ]
  • Abnormal hearing screening test [ Time Frame: By Day 90 post-initiation of vancomycin therapy ]
  • 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 ]
  • 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)
  • 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.
  • Relationship between CoNS species and duration of treatment and CRP response [ Time Frame: Day 5±1 or Day 10±1 ]
  • 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 ]
  • 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 ]
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neonatal Vancomycin Trial
Official Title  ICMJE 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
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
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Late Onset Neonatal Sepsis
Intervention  ICMJE 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.
Study Arms  ICMJE
  • 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

    Intervention: Drug: Vancomycin
  • 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
    Intervention: Drug: Vancomycin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 31, 2016)
300
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 1, 2019
Estimated Primary Completion Date December 1, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE up to 90 Days   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Louise Hill, MBChB MRCPCH 0208 725 4851 ext 4851 lhill@sgul.ac.uk
Listed Location Countries  ICMJE Estonia,   Greece,   Italy,   Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02790996
Other Study ID Numbers  ICMJE NeoVanc
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party PENTA Foundation
Study Sponsor  ICMJE PENTA Foundation
Collaborators  ICMJE
  • 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  ICMJE
Study Chair: Mike Sharland, MD, FRCPCH St George's, University of London
PRS Account PENTA Foundation
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP