Neonatal Vancomycin Trial

NCT02790996 | Terminated Phase 2 DMC

• 1 other identifier: NeoVanc
• Study Type: interventional
• Target: 242
• Locations: 4 countries
• Sites: 15

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

Conditions

Late Onset Neonatal Sepsis

Keywords

sepsis; neonate; vancomycin

Outcome Measures

Primary Outcomes (1)

• 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.

  10±1 days after End of Actual Vancomycin Therapy

Secondary Outcomes (11)

• Clinically or microbiologically significant relapse or new infection requiring treatment with any other antibiotic for more than 24 hours

  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

  Day 5±1 or Day 10±2

• Abnormal renal function tests at the Short-term Follow-Up Visit

  30±5 days post-initiation of vancomycin therapy

• Abnormal hearing screening test

  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

  30±5 days post-initiation of vancomycin therapy

Study Arms (2)

Vancomycin - Optimised Regimen

EXPERIMENTAL

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 - Standard Regimen

ACTIVE COMPARATOR

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

Vancomycin DRUG

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.

Vancomycin - Optimised Regimen; Vancomycin - Standard Regimen

Eligibility Criteria

• Age: 72 Hours - 90 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• PENTA Foundation: lead
• St George's, University of London: collaborator
• Hopital Universitaire Robert-Debre: collaborator
• University of Tartu: collaborator
• Consorzio per Valutazioni Biologiche e Farmacologiche: collaborator
• University of Liverpool: collaborator
• Therakind limited: collaborator
• Bambino Gesù Hospital and Research Institute: collaborator
• Servicio Madrileño de Salud, Madrid, Spain: collaborator
• Aristotle University Of Thessaloniki: collaborator
• Cardiff University: collaborator
• SYNAPSE Research Management Partners S.L: collaborator
• European Commission: collaborator

Study Sites (18)

Tallinn's Children's Hospital

Tallinn, Estonia

Location

Paediatric Intensive Care Unit, Clinicum of the University of Tartu

Tartu, Estonia

Location

Aghia Sophia Children's Hospital (A)

Athens, Greece

Location

Aghia Sophia Children's Hospital (B)

Athens, Greece

Location

Aghia Sophia Children's Hospital (C)

Athens, Greece

Location

Kyriakou Children's Hospital

Athens, Greece

Location

General University Hospital Attikon

Chaïdári, Greece

Location

Hippokration Hospital - Department of Neonatology

Thessaloniki, Greece

Location

Papageorgiou 2nd Department of Neonatology

Thessaloniki, Greece

Location

Ospedale "Di Venere" - Carbonara di Bari

Bari, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda

Milan, Italy

Location

Azienda Ospedaliera di Padova

Padua, Italy

Location

Policlinico San Matteo

Pavia, Italy

Location

Ospedale Pediatrico Bambino Gesu'

Rome, Italy

Location

Hospital Sant Joan de Deu

Barcelona, Spain

Location

Hospital 12 de Octubre

Madrid, Spain

Location

Hospital Materno Infantil, La Paz

Madrid, Spain

Location

St Mary's Hospital

Manchester, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 32293527 BACKGROUND

• 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.

  PMID: 34843669 DERIVED

MeSH Terms

Conditions

Neonatal Sepsis; Sepsis

Interventions

Vancomycin

Condition Hierarchy (Ancestors)

Infections; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Mike Sharland, MD, FRCPCH

  St George's, University of London

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2016
• First Posted: June 6, 2016
• Study Start: February 27, 2017
• Primary Completion: April 1, 2020
• Study Completion: April 1, 2020
• Last Updated: September 9, 2020

Record last verified: 2020-09

Locations

GB (1); ES (2); IT (5); GR (7)