Condition category
Nervous System Diseases
Date applied
30/05/2018
Date assigned
26/06/2018
Last edited
23/10/2020
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Every year at least 15,000 newborns undergo a lumbar puncture to confirm suspected meningitis. Lumbar puncture technique varies in practice, and success rates are low (50-60%) meaning procedures need to be repeated, causing distress to the infants and their parents and extending treatment and hospital stay time. There is a pressing need for a large study to determine which lumbar puncture technique is the best approach. The aim of this study is to compare lumbar puncture techniques with the infant in a sitting position versus a lying position, and early versus late stylet removal.

Who can participate?
Newborns and infants in neonatal units and maternity wards who are having a lumbar puncture

What does the study involve?
The participants are randomly allocated to one of the following technique combinations:
1. Lying position and early stylet removal
2. Sitting position and early stylet removal
3. Lying position and late stylet removal
4. Sitting position and late stylet removal
The proportion of successful lumbar punctures is measured in the four groups.

What are the possible benefits and risks of participating?
The results of this trial will inform best practice, and ultimately, improved technique would result in fewer uninterpretable samples, fewer repeated procedures, reduced distress for infants and families, decreased antibiotic use and risk of antibiotic resistance, and reduced NHS costs due to fewer procedures, reduced length of stay, shorter antibiotic courses, and minimised antibiotic-associated complications. All of the methods used in the study are used routinely within UK hospitals. At the moment it is not known whether one method is better than others, so babies taking part could be given any of them.

Where is the study run from?
The University of Oxford (UK)

When is the study starting and how long is it expected to run for?
September 2017 to February 2021

Who is funding the study?
National Institute for Health Research (NIHR) (UK)

Who is the main contact?
Rachel Williams
neoclear@npeu.ox.ac.uk

Trial website

https://www.npeu.ox.ac.uk/neoclear

Contact information

Type

Scientific

Primary contact

Ms Rachel Williams

ORCID ID

Contact details

NPEU
Richard Doll Building
Old Road Campus
Headington
Oxford
OX3 7LF
United Kingdom
+44 (0)1865289278
neoclear@npeu.ox.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

35643

Study information

Scientific title

NeoCLEAR: Neonatal Champagne Lumbar punctures Every time – An RCT. A multicentre, randomised controlled 2x2 factorial trial to investigate techniques to increase lumbar puncture success

Acronym

NeoCLEAR

Study hypothesis

Every year at least 15,000 newborns undergo a lumbar puncture to confirm suspected meningitis. Lumbar puncture technique varies in practice, and success rates are low (50-60%) meaning procedures need to be repeated, causing distress to the infants and their parents and extending treatment and hospital stay time. There is a pressing need for a large randomised controlled trial to determine which lumbar puncture technique is the best approach.

The trialists have designed a pragmatic (i.e a low level of trial-driven standards is enforced and sites work to their standard practices and processes for generalisability of the trial results), multi-centre, randomised controlled trial comparing two traditional lumbar puncture techniques:
1. The infant in sitting position versus lying position
2. Early versus late stylet removal

The aim is to determine the optimal technique for performing lumbar puncture in infants. The results of this trial will inform best practice, and ultimately, improved technique would result in:
1. Fewer uninterpretable samples
2. Fewer repeated procedures
3. Reduced distress for infants & families
4. Decreased antibiotic use and risk of antibiotic resistance
5. Reduced NHS costs due to fewer procedures, reduced length of stay, shorter antibiotic courses, and minimised antibiotic-associated complications

Ethics approval

South Central Hampshire-B, 12/06/2018, ref: 18/SC/0222

Study design

Randomised; Interventional; Design type: Diagnosis, Other

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Diagnostic

Patient information sheet

https://www.npeu.ox.ac.uk/neoclear/parents

Condition

Meningitis

Intervention

Stratified block randomisation will be used to ensure balance between the groups with respect to the collaborating hospital and corrected gestational age at trial entry.

The interventions compare:
1. Sitting position, in which the infant is held in a sitting position compared to lying (‘lateral decubitus’) position
2. Early stylet removal, which is the removal of the stylet from the hollow lumbar puncture needle shaft once it has penetrated the subcutaneous tissue before advancing the needle into the cerebrospinal fluid, compared to late stylet removal, which is removal of the stylet once it has been inserted into the expected cerebrospinal fluid space

The participants will be randomly allocated (with equal chance i.e. 1:1:1:1) to one of the following technique combinations:
1. Lying position and early stylet removal
2. Sitting position and early stylet removal
3. Lying position and late stylet removal
4. Sitting position and late stylet removal

Infants will be followed up until they are discharged home.

Intervention type

Procedure/Surgery

Phase

Drug names

Primary outcome measure

Proportion of infants with successful lumbar punctures, measured by whether cerebrospinal fluid is obtained and red blood cell count <10,000/mm3 on the first lumbar puncture procedure

Secondary outcome measures

Current secondary outcome measures as of 24/04/2020:
The following short-term clinical, resource and safety outcomes have been defined as:
1. The proportion of infants with:
1.1. No cerebrospinal fluid (CSF) obtained, or pure blood/clotted, or blood-stained, or clear
1.2. CSF obtained and red blood cell (RBC) count <500, <5000, <10,000, or <25,000/mm3, or any RBC count
1.3. A CSF white blood cell (WBC) count not requiring a correction (whatever the RBC count)
2. Total number of procedures and attempts performed per infant
3. Proportion of infants diagnosed (by WBC count criteria, culture, Gram stain, and/or clinically) via CSF with:
3.1. Meningitis: WBC count 20 or more in CSF, or a true positive culture/polymerase chain reaction (PCR) (if RBC count is ≥500, the WBC count will be reduced by 1 for every 500 RBC counts to give a 'corrected' WBC count)
3.2. Equivocal: WBC count (or corrected WBC) <20, AND negative (or contaminated/incidental) culture and PCR with:
3.2.1. Polymorphonuclear leukocytes (PMN) >2 (and RBC count <500) OR
3.2.2. Organism found on Gram stain
3.3. Negative: WBC (or corrected WBC) count <20, PMN ≤2 (if RBC count <500), and negative (or contaminated/incidental) cultures, PCR, and Gram stain
3.4. Uninterpretable: No CSF obtained, or clotted, or CSF so bloody or insufficient that a cell count was impossible
4. CSF WBC, RBC, corrected WBC counts, PMNs and lymphocytes from the clearest sample
5. Time taken on first procedure from start of cleaning skin to removing needle at end of all attempts
6. Infant movement on first procedure using basic 4-point scale

Outcomes relating to cost and safety:
7. In all infants, according to CSF-defined and clinically-defined diagnostic criteria:
7.1. Duration of the antibiotic course
7.2. Length of stay in surviving infants
7.3. Immediate complications related to LP:
7.3.1. Cardiovascular instability including oxygen saturations and heart rate
7.3.2. Respiratory deterioration (escalating respiratory support) post-LP
8. For the pilot phase: parental anxiety assessed using the State Trait Anxiety Inventory - State Subscale (STAI-S) Questionnaire

Previous secondary outcome measures:
Short-term clinical outcomes are measured by assessing:
1. The proportion of infants with:
1.1. No cerebrospinal fluid (CSF) obtained, or Pure blood/Clotted, or blood-stained, or clear
1.2. CSF obtained and red blood cell (RBC) count <500, <5,000, <10000, or <25000 /mm3, or any RBC count
1.3. A CSF white cell count not requiring a correction (whatever the RBC count)
2. Total number of procedures, and attempts within procedures, performed per infant to obtain interpretable CSF (RBC counts at the above thresholds)
3. Proportion of infants diagnosed (by WBC count criteria, culture, gram stain, and/or clinically) via CSF with:
3.1. Meningitis: WBC count 20 or more in CSF, or more than 2 PMNs, or a positive culture or gram stain, or clinically diagnosed (if RBC count is >500, the WBC count will be reduced by 1 for every 500 RBC counts to give a ‘corrected’ WBC count)
3.2. Equivocal: borderline white blood cell (WBC) counts, or uncertain culture result or uncertain clinical diagnosis
3.3. Negative: <20 CSF WBC count and 0–2 PMNs and negative cultures and gram stain and no clinical diagnosis of meningitis
3.4. Uninterpretable: no CSF obtained, or CSF so bloody that a cell count was impossible
4. CSF WBC, RBC, corrected WBC counts, PMNs, and lymphocytes, for any of the above
5. Time taken from start of cleaning skin to removing needle at end of all attempts
6. Infant movement assessed using a basic 4-point scale at time of procedure
7. Parental anxiety, measured using short-version STAI at baseline and within 48 hours of the first lumbar puncture procedure
8. Cost measured by assessing the duration of the antibiotic course from trial entry to discharge home
9. Cost measured by assessing the length of stay in hospital from trial entry until discharge home
10. Safety measured by assessing cardiovascular instability, including oxygen saturations and heart rate during the lumbar puncture procedure
11. Safety measured by assessing respiratory deterioration based on the requirement for escalating respiratory support within 1 hour of the lumbar puncture procedure

Overall trial start date

01/09/2017

Overall trial end date

28/02/2021

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

1. Neonates and infants in neonatal units and their maternity wards who are having a lumbar puncture
2. Parent(s) willing and able to give informed consent
3. Infants of corrected gestational age from 27+0 weeks to 44+0 weeks, AND working weight of 1,000 g or more
4. First lumbar puncture for current indication

Participant type

Patient

Age group

Neonate

Gender

Both

Target number of participants

Planned Sample Size: 1,020; UK Sample Size: 1,020

Participant exclusion criteria

Current exclusion criteria as of 24/04/2020:
1. Unable to be held in sitting position (including infants intubated and mechanically-ventilated) or other clinical condition which is likely, in the opinion of the treating clinician, to make sitting difficult, or which is likely to be compromised by sitting (e.g.open gastroschisis)
2. Previously randomised to the trial

Previous exclusion criteria:
1. Unable to be held in sitting position (e.g. intubated and mechanically-ventilated) or other clinical condition which is likely to make sitting difficult, or which is likely to be compromised by sitting (e.g. open gastroschisis)
2. Previously randomised to the trial

Recruitment start date

01/06/2018

Recruitment end date

31/08/2020

Locations

Countries of recruitment

United Kingdom

Trial participating centre

John Radcliffe Hospital (lead site)
Headley Way Headington
Oxford
OX3 9DU
United Kingdom

Trial participating centre

Birmingham Heartlands Hospital
Bordesley Green East
Birmingham
B9 5SS
United Kingdom

Trial participating centre

Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom

Trial participating centre

Northampton General Hospital
Cliftonville
Northampton
NN1 5BD
United Kingdom

Trial participating centre

Princess Anne Hospital
Coxford Road
Southampton
SO16 5YA
United Kingdom

Trial participating centre

Royal Berkshire Hospital
London Road
Reading
RG1 5AN
United Kingdom

Trial participating centre

Royal Hampshire County Hospital
Department of Paediatrics
Winchester
SO22 5DG
United Kingdom

Trial participating centre

Southmead Hospital
Southmead road Westbury-on-Trym
Bristol
BS10 5NB
United Kingdom

Trial participating centre

St Michael's Hospital
Southwell Street
Bristol
BS2 8EG
United Kingdom

Trial participating centre

Bradford Royal Infirmary
Smith Lane
Bradford
BD9 6DA
United Kingdom

Trial participating centre

Colchester General Hospital
Turner Rd Mile End
Colchester
CO4 5JL
United Kingdom

Trial participating centre

Derriford Hospital
Derriford Rd
Plymouth
PL6 8DH
United Kingdom

Trial participating centre

Gloucestershire Royal Hospital
Great Western Rd
Gloucester
GL1 3NN
United Kingdom

Trial participating centre

Great Western Hospital
Marlborough Rd
Swindon
SN3 6BB
United Kingdom

Trial participating centre

Medway Maritime Hospital
Windmill Road
Gillingham
ME7 5NY
United Kingdom

Trial participating centre

Norfolk and Norwich University Hospital
Colney Lane
Norwich
NR4 7UY
United Kingdom

Trial participating centre

Royal Devon and Exeter Hospital
Barrack Rd
Exeter
EX2 5DW
United Kingdom

Trial participating centre

Royal Oldham Hospital
Rochdale Rd
Oldham
OL1 2JH
United Kingdom

Trial participating centre

St Peter's Hospital
Guildford Rd Lyne
Chertsey
KT16 0PZ
United Kingdom

Trial participating centre

Stoke Mandeville Hospital
Mandeville Rd
Aylesbury
HP21 8AL
United Kingdom

Trial participating centre

Basingstoke and North Hampshire Hospital
Aldermaston Rd
Basingstoke
RG24 9NA
United Kingdom

Sponsor information

Organisation

University of Oxford

Sponsor details

Clinical Trials & Research Governance
Boundary Brook House
Churchill Drive
Headington
OX3 7LQ
United Kingdom
-
ctrg@admin.ox.ac.uk

Sponsor type

University/education

Website

Funders

Funder type

Government

Funder name

NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: 15/188/106

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

The study protocol and other documentation will be made available on the trial website: https://www.npeu.ox.ac.uk/neoclear. Planned publication of the study results in a high-impact peer reviewed journal.

IPD sharing statement
The data sharing plans for the current study are unknown and will be made available at a later date.

Intention to publish date

28/02/2021

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

2020 protocol in https://pubmed.ncbi.nlm.nih.gov/32295554/ (added 24/04/2020)

Publication citations

Additional files

Editorial Notes

23/10/2020: The plain English summary was updated to reflkect the change to the overall trial end date in 29/07/2020. 05/08/2020: The intention to publish date was changed from 31/08/2020 to 28/02/2021. 29/07/2020: The following changes were made to the trial record: 1. The recruitment resumed. 2. The recruitment end date was changed from 31/05/2020 to 31/08/2020. 3. The overall end date was changed from 30/04/2020 to 28/02/2021. 24/04/2020: The following changes have been made: 1. Due to current public health guidance, recruitment for this study has been paused. 2. Bradford Royal Infirmary, Colchester General Hospital, Derriford Hospital, Gloucestershire Royal Hospital, Great Western Hospital, Medway Maritime Hospital, Norfolk and Norwich University Hospital, Royal Devon and Exeter Hospital, Royal Oldham Hospital, St Peter's Hospital, Stoke Mandeville Hospital and Basingstoke and North Hampshire Hospital have been added to the trial participating centres. 3. The participant information sheet field has been updated. 4. The secondary outcome measures have been updated. 5. The participant exclusion criteria have been changed. 6. The recruitment end date has been changed from 31/08/2020 to 30/04/2020. 7. Publication reference added. 22/03/2019: The condition was updated from "Specialty: Children, Primary sub-specialty: Methodology; UKCRC code/ Disease: Neurological/ Inflammatory diseases of the central nervous system" to "meningitis".