TerminatedNCT02790996NeoVancUpdated Sep 9, 2020

Neonatal Vancomycin Trial

A Phase 2 interventional study of Vancomycin in Late Onset Neonatal Sepsis, sponsored by PENTA Foundation. Terminated at 18 sites in 5 countries. Open to participants aged 72 Hours to 90 Days. Per ClinicalTrials.gov, last updated 2020-09-09.

Sponsored by PENTA Foundation · Phase 2, Interventional, and Treatment

Why this study was terminated

Planned interim analysis yielded different event rate affecting sample size and ability to recruit sufficient numbers within remaining trial time frame

Phase: Phase 2
Study type: Interventional
Enrollment: 242
Allocation: Randomized
Ages: 72 Hours to 90 Days
Sex: All

Study 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

Read the 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

Conditions studied

Late Onset Neonatal Sepsis

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Keywords

sepsis
neonate
vancomycin

In context

Sepsis

1,899 studies on the registry are indexed under Sepsis; 462 are open to participants now.

This study's enrollment of 242 is above the median of 105 across 896 interventional studies indexed under Sepsis.

Browse Sepsis studies →

Lead sponsor

PENTA Foundation is the lead sponsor of 22 studies on the registry; 3 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 72 Hours to 90 Days
Sexes eligible: All
Accepts healthy volunteers: No

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

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

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 242 participants (actual)

Study arms

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
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

Interventions

DrugVancomycin
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.

What researchers measure

Primary outcomes

Successful outcome at Test of Cure visit
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.
Time frame: 10±1 days after End of Actual Vancomycin Therapy

Secondary outcomes

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
Area under the plasma concentration time curve - AUC (mg\*hour/L)
Time frame: Up to 2 years (final data collection date for outcome measure)
Probability of target attainment (PTA) with different study regimens
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.
Time frame: Up to 2 years (final data collection date for outcome measure)
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
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
Time frame: Day 3 and Day 5±1, Day 10±1 (standard arm only)

Study locations

18 sites

Tallinn's Children's Hospital
Tallinn, Estonia
Paediatric Intensive Care Unit, Clinicum of the University of Tartu
Tartu, Estonia
Aghia Sophia Children's Hospital (A)
Athens, Greece
Aghia Sophia Children's Hospital (B)
Athens, Greece
Aghia Sophia Children's Hospital (C)
Athens, Greece
Kyriakou Children's Hospital
Athens, Greece
General University Hospital Attikon
Chaïdári, Greece
Hippokration Hospital - Department of Neonatology
Thessaloniki, Greece
Papageorgiou 2nd Department of Neonatology
Thessaloniki, Greece
Ospedale "Di Venere" - Carbonara di Bari
Bari, Italy
ASST Grande Ospedale Metropolitano Niguarda
Milan, Italy
Azienda Ospedaliera di Padova
Padova, Italy
Policlinico San Matteo
Pavia, Italy
Ospedale Pediatrico Bambino Gesu'
Rome, Italy
Hospital Sant Joan de Deu
Barcelona, Spain
Hospital 12 de Octubre
Madrid, Spain
Hospital Materno Infantil, La Paz
Madrid, Spain
St Mary's Hospital
Manchester, United Kingdom

References and documents

Publications

Hill LF, Turner MA, Lutsar I, Heath PT, Hardy P, Linsell L, Jacqz-Aigrain E, Roilides E, Sharland M; NeoVanc Consortium. An optimised dosing regimen versus a standard dosing regimen of vancomycin for the treatment of late onset sepsis due to Gram-positive microorganisms in neonates and infants aged less than 90 days (NeoVanc): study protocol for a randomised controlled trial. Trials. 2020 Apr 15;21(1):329. doi: 10.1186/s13063-020-4184-8. PubMed 32293527 ↗
Hill LF, Clements MN, Turner MA, Dona D, Lutsar I, Jacqz-Aigrain E, Heath PT, Roilides E, Rawcliffe L, Alonso-Diaz C, Baraldi E, Dotta A, Ilmoja ML, Mahaveer A, Metsvaht T, Mitsiakos G, Papaevangelou V, Sarafidis K, Walker AS, Sharland M; NeoVanc Consortium. Optimised versus standard dosing of vancomycin in infants with Gram-positive sepsis (NeoVanc): a multicentre, randomised, open-label, phase 2b, non-inferiority trial. Lancet Child Adolesc Health. 2022 Jan;6(1):49-59. doi: 10.1016/S2352-4642(21)00305-9. Epub 2021 Nov 26. PubMed 34843669 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 9, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02790996
Lead sponsor: PENTA Foundation
Collaborators: St George's, University of London, Hopital Universitaire Robert-Debre, 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, Cardiff University, SYNAPSE Research Management Partners S.L, European Commission
Responsible party: Sponsor
First posted: Jun 6, 2016
Start date: Feb 27, 2017
Primary completion: Apr 1, 2020
Completion: Apr 1, 2020
Last update: Sep 9, 2020

Study contacts

Mike Sharland, MD, FRCPCH

study chair · St George's, University of London

Oversight

Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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