PREVAIL study - PREVenting infection using Antimicrobial Impregnated Long lines

ISRCTN	ISRCTN81931394
DOI	https://doi.org/10.1186/ISRCTN81931394
Protocol serial number	HTA 12/167/02; 12EB13
Sponsor	Great Ormond Street Hospital for Children NHS Foundation Trust (UK)
Funder	NIHR Health Technology Assessment Programme - HTA (UK)

Submission date: 13/11/2014
Registration date: 21/11/2014
Last edited: 02/05/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Neonatal Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
A peripherally inserted central catheter (PICC) is a long, thin tube that goes into a vein in the upper arm. Babies in neonatal units often need to take medicines and fluids through PICCs for a long time. PICCs are inserted in order to avoid the need for repeated painful procedures and can stay in place for several weeks. However, very occasionally these PICCs can cause infections in the blood. There are currently two types of PICCs available. One type is coated with an antibiotic and an antifungal which might prevent infection by killing bacteria (AM-PICC), and the other type is not (a standard PICC). Although both are available, currently hospitals tend to use the standard PICC (S-PICC). We are currently investigating antimicrobial catheters in children, however, we also need to find out which catheter (PICC) is better in babies or if there is no difference between them. The study will help hospitals to decide which type of PICC to use for babies admitted to neonatal intensive care in the future.

Who can participate?
Babies who require the narrowest PICC.

What does the study involve?
Participating babies will be randomly allocated to be treated with either an AM-PICC or a S-PICC. The study will follow your baby using routine records and will use infection results from samples that need to be taken as part of your baby's routine clinical care. When your baby's PICC is removed, we will also test the tip for bacteria. Information will also be collected from the babies' hospital admission up till 6 months after they have entered the study.

What are the possible benefits and risks of participating?
Both PICCs are CE marked for use in babies which means they comply with EU legislation. Currently normal practise in hospitals is to use the standard PICCs; however, there is no evidence to support that these are better or worse than AM-PICC. For all PICCs there is a small risk that they may become infected and cause an infection in the blood. By using the antimicrobial PICCs this risk of infection may decrease. As the antimicrobial PICCs do contain a tiny amount of antibiotic and antifungal, there is a potential that instead of being beneficial they could be problematic. However, the main foreseeable disadvantage, that bacteria/fungi might become resistant to the antibiotic/antifungal, is very unlikely indeed to have any impact on a baby's care.

Where is the study run from?
The study will be run from 18 neonatal units in the UK. The lead centre will be Bradford Teaching Hospitals NHS Foundation Trust. The study will be co-ordinated through the Medicines for Children Clinical Trials Unit, University of Liverpool.

When is the study starting and how long is it expected to run for?
The study will run from December 2014 until August 2017.

Who is funding the study?
NIHR Health Technology Assessment Programme - HTA (UK).

Who is the main contact?
Professor Ruth Gilbert and Dr Sam Oddie
prevail@liverpool.ac.uk

Contact information

Prof Ruth Gilbert
Scientific

MRC Centre of Epidemiology for Child Health
UCL Institute of Child Health
30 Guilford Street
London
WC1N 1EH
United Kingdom

Email	r.gilbert@ucl.ac.uk

Study information

Primary study design	Interventional
Study design	Unblinded two-arm randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title	An unblinded, two-arm randomised controlled trial to determine the effectiveness and cost-effectiveness of antimicrobial impregnated (with rifampicin and miconazole) long lines (termed peripherally inserted central venous catheters, or AM-PICC) compared with standard PICC (S-PICC) for reducing blood stream infection (BSI)
Study acronym	PREVAIL
Study objectives	The overall aim of the study is to determine whether AM-PICC should be introduced across the NHS for preterm babies. In very preterm infants, does the use of antimicrobial impregnated PICC, compared to standard PICC, reduce blood stream infection and is it cost effective? More details can be found at http://www.nets.nihr.ac.uk/projects/hta/1216702
Ethics approval(s)	NRES Committee -Yorkshire & The Humber - Sheffield, 31/10/2014, Ref: 14/YH/1202
Health condition(s) or problem(s) studied	Infectious disease, preterm babies requiring a PICC
Intervention	1. Antimicrobial impregnated (with rifampicin and miconazole) peripherally inserted central venous catheters (AM-PICC) 2. Standard PICC (S-PICC)
Intervention type	Device
Phase
Drug / device / biological / vaccine name(s)
Primary outcome measure(s)	Time to first blood stream infection based on a positive blood culture (including fungal BSI) taken between 24 hours after randomisation until 48 hours after removal. As part of the primary endpoint there will be two sensitivity analyses: 1. A sensitivity analysis confined to clinically serious BSI defined by positive culture and the baby is treated for more than 72 hours with intravenous antibiotics or dies during treatment 2. Time to first BSI based on a positive blood culture (including fungal BSI) taken between 24 hours after PICC insertion until 48 hours after removal
Key secondary outcome measure(s)	1. Rifampicin or miconazole resistance in any isolate from blood culture 2. Rifampicin or miconazole resistance in any isolate from PICC tips 3. Death within 6 months of randomisation 4. Death before discharge 5. Rate of BSI per 1000 PICC-days (including recurrent BSI) 6. Rate of one or more BSI 7. Rate of catheter-related BSI 8. Time to a composite measure of BSI including culture-negative BSI (based on reason for antibiotic treatment beyond 72 hours after a negative blood culture sample) 9. Rate of blood culture sampling per 1000 PICC days 10. Duration of antimicrobial exposure from randomisation up to 48 hours after line removal 11. Rate of chronic lung disease 36 weeks postmenstrual age 12. Rate of necrotizing enterocolitis (NEC): Bells stage II or III 13. Rate for treatment for retinopathy of prematurity before NNU discharge 14. Rate of abnormalities on cranial ultrasound 15. Time to full milk feeds after randomisation 16. Breast milk intake at discharge from NNU 17. Total duration of parenteral nutrition from randomisation until discharge from NNU 18. Time to PICC removal
Completion date	31/08/2017

Eligibility

Participant type(s)	Patient
Age group	Neonate
Sex	All
Target sample size at registration	858
Total final enrolment	861
Key inclusion criteria	1. Babies who require a PICC (Premicath 1 Fr) 2. Admitted to a NNU that is recruiting for this trial 3. Parent/legal representative of the baby gives informed written consent for the trial Note: Babies with the following can be included in the trial: 1. Congenital malformations 2. Gastrointestinal surgical conditions 3. Previous PICC (non-trial PICC) 4. Previously treated BSI which has resolved in the opinion of the Investigator
Key exclusion criteria	1. Baby has been previously entered into this trial 2. Baby has a known allergy or hypersensitivity to rifampicin or miconazole
Date of first enrolment	01/06/2015
Date of final enrolment	31/05/2017

Locations

Countries of recruitment

United Kingdom
England

Study participating centres

Birmingham Women's Hospital

Birmingham
B15 2TG
United Kingdom

Bradford Royal Infirmary

Bradford
BD9 6RJ
United Kingdom

Homerton Hospital

London
E9 6SR
United Kingdom

John Radcliffe Hospital

Oxford
OX3 9DU
United Kingdom

Leeds General Infirmary

Leeds
LS1 3EX
United Kingdom

Leicester Royal Infirmary

Leicester
LE1 5WW
United Kingdom

Liverpool Women's Hospital

Liverpool
L8 7SS
United Kingdom

Newham University Hospital

Plaistow
E13 8SL
United Kingdom

Nottingham City Hospital

Nottingham
NG5 1PB
United Kingdom

Nottingham University Hospital (QMC)

Nottingham
NG7 2UH
United Kingdom

Queen's Hospital

Romford
RM7 0AG
United Kingdom

Royal Bolton Hospital

Bolton
BL4 0JR
United Kingdom

Royal Oldham Hospital

Oldham
OL1 2JH
United Kingdom

Royal Preston Hospital

Preston
PR2 9HT
United Kingdom

St Mary's Hospital

Manchester
M13 0JH
United Kingdom

St Michael's Hospital

Bristol
BS2 8EG
United Kingdom

The Jessop Wing

Sheffield
S10 2SF
United Kingdom

The Royal London Hospital

London
E1 1BB
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not expected to be made available
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/06/2019	02/05/2019	Yes	No
HRA research summary			28/06/2023	No	No
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

02/05/2019: The following changes were made to the trial record:
1. Publication reference added.
2. The total final enrolment was added.