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Trial registered on ANZCTR


Registration number
ACTRN12614000092695
Ethics application status
Approved
Date submitted
9/01/2014
Date registered
23/01/2014
Date last updated
18/03/2019
Date data sharing statement initially provided
18/03/2019
Date results information initially provided
18/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A randomised double-blind controlled trial of lignocaine/phenylephrine nasal spray vs placebo for pain and distress of nasogastric tube insertion in children
Scientific title
A randomised double-blind controlled trial of lignocaine/phenylephrine nasal spray vs placebo for pain and distress of nasogastric tube insertion in children
Secondary ID [1] 283881 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Distress associated with insertion of nasogastric tube in children (aged 6 months-5 years) 290866 0
Condition category
Condition code
Public Health 291224 291224 0 0
Health service research

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Study drugs
Intranasal lignocaine / phenylephrine spray is available proprietary product which contains the active ingredients of lignocaine hydrochloride 50 mg/mL and phenylephrine hydrochloride 5 mg/mL. It is administered by a pump actuated topical spray.

The nozzle spray attachment provides 100 micolitres per spray. This results in each spray providing 5mg lignocaine and 0.5mg phenylephrine.

Placebo spray (0.9% sodium chloride)
Prepared and packaged in an identical manner to study drug (lignocaine / phenylephrine)

Dosing schedule for blinded administration of intranasal lignocaine / phenylephrine or saline placebo.(1, 2)

* 6 kg – 12 kg 1 spray per nostril
* >12 kg 2 sprays per nostril


Medication preparation, storage and use-monitoring
Spray bottles will be prepared and checked in a clean area by manufacturing service pharmacists in the pharmacy department at MMC Clayton.

Lignocaine / phenylephrine spray bottles will be made by transferring 2.5mL of CoPhenylcaine Forte into a spray bottle. This will then be labelled and kept in a sealed plastic bag until use.

Placebo spray bottles will be made by transferring 2.5mL of sodium chloride 0.9% for irrigation into a spray bottle. This will again be labelled and kept in a sealed plastic bag until use.

Spray bottle numbers, constituents, their batch number, expiry will be recorded by sterile manufacturing and clinical trials pharmacy. A prescription marked with the corresponding spray bottle number will be included in each bag - for return to pharmacy for study accountability.

The study spray bottles will be given an expiry of one month from manufacture. Twenty spray bottles will be prepared monthly by pharmacy. Each month unused spray bottles will be deemed expired and destroyed by pharmacy. Spray bottle numbers not used will be documented and later re-made (with the same allocation) until all 100 spray bottle numbers are accounted for. If recruitment of patients is in excess of 5 per week, spray bottle number production will be reviewed and may increase up to a maximum of eight per week.

Labelling
In order to avoid administration errors in the emergency department, the drug will be prominently labelled with “Not for injection, for intranasal use only.”

Each spray bottle and outer bag will be labelled with the spray bottle number and instructions for dose and usage as follows:

CoPhenylcaine (lignocaine 5mg/spray and phenylephrine 0.5mg/spray) OR Placebo (0.9% sodium chloride solution) [MMC project no: XXXXXX] 2.5mL

Administer spray from study weight / dose table, using supplied spray bottle and nozzle.
Spray bottle no:.............. Batch:.............................. Expiry:......................


Storage
CoPhenylcaine is a Schedule 2 (S2) medication. As such, the study medication will be stored in a locked drug room in the paediatric emergency department.

Prescriptions will include the study drug and number of sprays to be administered.

Refrences
1. Lignocaine. Australian Medicines Handbook 2013 (Online). Adelaide: Australian Medicines Handbook Pty Ltd; 2013.
2. CoPhenylcaine Forte Mims Online [Internet]. St Leonards, NSW: UBM Medica; 2013.
Intervention code [1] 288555 0
Treatment: Drugs
Comparator / control treatment
Placebo (normal saline (0.9%w/v) nasal spray)
Control group
Placebo

Outcomes
Primary outcome [1] 291218 0
Primary outcome measure
- Faces, Legs, Activity, Cry and Consolability (FLACC) Scale during the procedure.
- The FLACC score was originally designed for assessment of post-operative pain in young children, and has been recommended in various reviews as a procedural pain score for preverbal and early verbal children.(1) It comprises five separate items (face, legs, activity, cry, and consolability), each of which is scored from 0 to 2. The five scores are then added to arrive at a score out of 10
- This will be assessed by a member of staff not directly involved in the insertion of the nasogastric tube at four times during the study

References
1.Manworren RCB, Hynan LS. Clinical validation of FLACC: preverbal patient pain scale. Pediatric Nursing.29(2):140-6.
Timepoint [1] 291218 0
* In ED cubicle prior to study drug administration
* In procedure room when child is positioned for NGT insertion (prior to insertion attempts)
* During final NGT insertion attempt
* Once child has been returned to ED cubicle
Secondary outcome [1] 306249 0
Procedural Staff Member to record visual analog scale (VAS) score for patient pain (e.g. No pain --> severe pain)
Timepoint [1] 306249 0
During final nasogastric tube insertion attempt
Secondary outcome [2] 306443 0
Procedural Staff Member to record visual analog scale (VAS) score for patient distress (e.g. No distress --> severe distress)
Timepoint [2] 306443 0
During final nasogastric tube insertion attempt
Secondary outcome [3] 306444 0
Procedural Staff Member to record visual analog scale (VAS) score for difficulty of insertion of NGT (e.g. Not at all difficult to insert --> Extremely difficult to insert)
Timepoint [3] 306444 0
During final nasogastric tube insertion attempt
Secondary outcome [4] 306509 0
Complication of study medication (nasal spray)-descriptive text
Timepoint [4] 306509 0
Prior to, during and immediately after final nasogastric tube attempt
Secondary outcome [5] 306512 0
Complication of NGT insertion (e.g. Bleeding / epistaxis, Tracheal placement, Vomiting, Other-descriptive text)
Timepoint [5] 306512 0
During/immediately after final nasogastric tube attempt
Secondary outcome [6] 306513 0
Number of attempts required to insert NGT
Timepoint [6] 306513 0
Immediately after final nasogastric tube attempt
Secondary outcome [7] 306518 0
Procedural staff member
Timepoint [7] 306518 0
During/immediately after final nasogastric tube attempt
Secondary outcome [8] 306519 0
Methods used to confirm placement of the NGT (e.g. Aspiration of contents, pH test of aspirate acidic, Insufflation / auscultation, X-ray, Other (descriptive text))
Timepoint [8] 306519 0
During/immediately after final nasogastric tube attempt
Secondary outcome [9] 306520 0
Judgement as to whether placebo or lignocaine / phenylephrine or placebo was administered
Timepoint [9] 306520 0
During/immediately after final nasogastric tube attempt
Secondary outcome [10] 306521 0
- Parent to record visual analog scale (VAS) scores for
Patient pain (e.g. No pain --> severe pain)
Timepoint [10] 306521 0
During final nasogastric tube insertion attempt
Secondary outcome [11] 306522 0
- Parent to record visual analog scale (VAS) scores for Patient distress (e.g. No distress --> severe distress)
Timepoint [11] 306522 0
During final nasogastric tube insertion attempt
Secondary outcome [12] 309924 0
Time between treatment (nasal spray) and successful nasogastric tube insertion
Timepoint [12] 309924 0
Time of nasal spray and time of procedure completion
Secondary outcome [13] 309925 0
Proceduralist experience will be assessed by indicating the number of procedures performed in the past 12 months
Timepoint [13] 309925 0
After final nasogastric tube attempt/insertion
Secondary outcome [14] 309926 0
Proceduralist confidence will be assessed using a visual analog scale (VAS) score.
Timepoint [14] 309926 0
After final nasogastric tube attempt/insertion

Eligibility
Key inclusion criteria
Children who are (1) aged 6 months to 5 years of age AND (2) weigh at least 6kg who are due to have a nasogastric tube inserted as part of their emergency department treatment.
Minimum age
6 Months
Maximum age
5 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
*Inability to gain informed consent from parent or guardian
*Indication for an urgent insertion of a nasogastric tube
*Accompanying adult is non-English speaking and no interpreter service is available
*Child or parent has an allergy to lignocaine or phenylephrine
*Aberrant nasal anatomy
*Acute or chronic nasal problems or nasal trauma that may preclude adequate administration or absorption of intranasal medication.
*Cardiovascular disease / congenital heart disease – specifically hypertension, severe bradycardia, conduction disturbances and digitalis intoxication
*Known hepatic or renal impairment
*Asthma (particularly sulfite-sensitive asthma)
*Genetic predisposition to malignant hyperthermiaPre-existing abnormal neurological conditions
*Child is taking medications known to interact with Co-phenylcaine Forte (Antiarrhythmic drugs;Suxamethonium; Phenytoin;Antidepressants; Propranolol;)Citicoline

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Recruitment
Emergency Physicians and trainees working in the ED will recruit a convenience sample of patients requiring a nasogastric tube that meet the inclusion and exclusion criteria. The recruitment target will be100 within 1 year.
Consent process
Written, informed consent will be obtained from parents or guardians before enrolment.
Parent information statements include references to possible side effects, including tremor, palpitations, or a bitter taste in the mouth.

Randomisation:-
It is expected to enrol 100 patients in the study, thus 100 spray bottle numbers will be randomly allocated to either lignocaine / phenylephrine or placebo. Randomisation will be made following a block randomisation table as described by Altman and Bland (1999).

Allocation will be concealed using numbered spray bottles
Each spray bottle number will be manufactured as allocated and this number will be recorded on the patient prescription accompanying the spray bottle.

Spray bottles will be prepared and checked in a clean area by manufacturing service pharmacists in the pharmacy department at MMC Clayton.

Lignocaine / phenylephrine spray bottles will be made by transferring 2.5mL of CoPhenylcaine Forte into a spray bottle. This will then be labelled and kept in a sealed plastic bag until use.

Placebo spray bottles will be made by transferring 2.5mL of sodium chloride 0.9% for irrigation into a spray bottle. This will again be labelled and kept in a sealed plastic bag until use.

Spray bottle numbers, constituents, their batch number, expiry will be recorded by sterile manufacturing and clinical trials pharmacy. A prescription marked with the corresponding spray bottle number will be included in each bag - for return to pharmacy for study accountability.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be made following a block randomisation table as described by Altman and Bland (1999).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Statistical Analysis
Baseline variables such as sex and age will be presented as number and percentage or median with interquartile range, and compared using either chi square or Mann Whitney tests as appropriate.
Primary and secondary outcome scores

FLACC scores and VAS scores will be presented as median and interquartile range (IQR). Non-normally distributed scores will be compared using a Wilcoxon rank-sum test and normally distributed data using a t test. Categorical data will be analyzed using a Fisher’s exact test.

Sample size
Assuming a standard deviation of 2.5, an alpha of 0.05, and a power of 90%, 35 patients per treatment arm are required to demonstrate a difference in FLACC score of 2 points. This difference has previously been considered the minimally clinically significant difference using this scoring system.(1) Allowing for attrition and other factors, a total of 100 patients is required (50 in each group).

Reference
1-Cole J, Shepherd M, Young P. Intranasal fentanyl in 1-3-year-olds: a prospective study of the effectiveness of intranasal fentanyl as acute analgesia. . Emerg Med Australas. 2009;21(5):395-400.)

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
31/07/2014
Actual
31/07/2014
Date of last participant enrolment
Anticipated
Actual
18/01/2018
Date of last data collection
Anticipated
Actual
18/01/2018
Sample size
Target
100
Accrual to date
Final
100
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 1942 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 7685 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 288524 0
Charities/Societies/Foundations
Name [1] 288524 0
Morson Taylor Research Award, Emergency Medicine Research Foundation, c/o Australasian College for Emergency Medicine
Country [1] 288524 0
Australia
Primary sponsor type
Individual
Name
Dr Simon Craig
Address
Dept. Emergency Medicine, Monash Medical Centre, 246 Clayton Rd, Clayton, Vic, 3168
Country
Australia
Secondary sponsor category [1] 287234 0
Individual
Name [1] 287234 0
Dr John Cheek
Address [1] 287234 0
Dept. Emergency Medicine, Monash Medical Centre, 246 Clayton Rd, Clayton , Vic, 3168.
Country [1] 287234 0
Australia
Other collaborator category [1] 277752 0
Individual
Name [1] 277752 0
Dr Diana Egerton-Warburton
Address [1] 277752 0
Dept. Emergency Medicine, Monash Medical Centre, 246 Clayton Rd, Clayton , Vic, 3168.
Country [1] 277752 0
Australia
Other collaborator category [2] 277753 0
Individual
Name [2] 277753 0
Dr Adam West
Address [2] 277753 0
Dept. Emergency Medicine, Monash Medical Centre, 246 Clayton Rd, Clayton , Vic, 3168.
Country [2] 277753 0
Australia
Other collaborator category [3] 277754 0
Individual
Name [3] 277754 0
Dr Robert Seith
Address [3] 277754 0
Dept Emergency Medicine, Monash Medical Centre, 246 Clayton Road, Clayton Vic 3168
Country [3] 277754 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290386 0
Monash Health Human Research Ethics Committee
Ethics committee address [1] 290386 0
Monash Medical Centre, 246 Clayton Rd, Clayton , Vic, 3168.
Ethics committee country [1] 290386 0
Australia
Date submitted for ethics approval [1] 290386 0
27/11/2013
Approval date [1] 290386 0
12/03/2014
Ethics approval number [1] 290386 0
13410A

Summary
Brief summary
Nasogastric tube insertion is consistently rated as one of the most painful and distressing procedures undertaken
in the emergency department. Multiple adult studies have demonstrated that use of local anaesthetic prior to
insertion markedly reduces this pain and distress, however, the only study undertaken in children did not show any
benefit.
We plan to undertake a randomised trial in children aged 6 months to 5 years of age. The trial will compare the
effects of a spray of salty water (saline) to a spray of local anaesthetic (lignocaine and phenylephrine) into the nose
prior to insertion of the nasogastric tube.
An observer will measure pain and distress experienced by the child before, during and after the procedure. The
child's carer will also be asked to rate the child's pain and distress.
Insertion of a nasogastric tube usually takes approximately 5-10 minutes. The anticipated duration of the study is 20-30
minutes, including time for explanation and consent.
Approximately 100 children will need to be recruited to complete the study
We hypothesise that lignocaine / phenylephrine spray and intranasal placebo spray will be equally effective in the prevention of pain and distress associated with nasogastric tube insertion in children
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 45426 0
Dr Simon Craig
Address 45426 0
Department Emergency Medicine, Monash Medical Centre, 246 Clayton Rd, Clayton, Vic, 3168
Country 45426 0
Australia
Phone 45426 0
+613 403 150 452
Fax 45426 0
+613 9594 6339
Email 45426 0
[email protected]
Contact person for public queries
Name 45427 0
Simon Craig
Address 45427 0
Department Emergency Medicine, Monash Medical Centre, 246 Clayton Rd, Clayton, Vic, 3168
Country 45427 0
Australia
Phone 45427 0
+613 403 150 452
Fax 45427 0
+61 3 9594 6339
Email 45427 0
[email protected]
Contact person for scientific queries
Name 45428 0
Simon Craig
Address 45428 0
Department Emergency Medicine, Monash Medical Centre, 246 Clayton Rd, Clayton, Vic, 3168
Country 45428 0
Australia
Phone 45428 0
+613 403 150 452
Fax 45428 0
+61 3 9594 6339
Email 45428 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23311Study protocol https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-015-0547-y 

Results publications and other study-related documents

Documents added manually
Current Study Results
No documents have been uploaded by study researchers.

Update to Study Results
Doc. No.TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
3960Plain language summaryNo No difference in procedure-related distress betwee... [More Details]
4452Study results articleYes Craig SS, Seith RW, Cheek JA, Wilson K, Egerton-Wa... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseLignocaine/phenylephrine nasal spray vs. placebo for the pain and distress of nasogastric tube insertion in children: A study protocol for a randomized controlled trial.2015https://dx.doi.org/10.1186/s13063-015-0547-y
EmbaseLidocaine and phenylephrine versus saline placebo nasal spray for the pain and distress of nasogastric tube insertion in young children and infants: a randomised, double-blind, controlled trial.2019https://dx.doi.org/10.1016/S2352-4642%2819%2930058-6
N.B. These documents automatically identified may not have been verified by the study sponsor.