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Trial registered on ANZCTR

Registration number

ACTRN12625000741482

Ethics application status

Approved

Date submitted

13/06/2025

Date registered

15/07/2025

Date last updated

15/07/2025

Date data sharing statement initially provided

15/07/2025

Type of registration

Prospectively registered

Titles & IDs

Public title

A randomised controlled trial of interventions to reduce the pain and distress of nasogastric tube insertion in young children.

Scientific title

A randomised controlled trial of interventions (topical intranasal lidocaine/ intranasal midazolam/ intranasal fentanyl/ usual care) to reduce the pain and distress of nasogastric tube insertion in young children.

Secondary ID [1]

MRFF - 2031095

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Pain management for nasogastric tube insertion

Condition category

Condition code

Emergency medicine

Other emergency care

Anaesthesiology

Pain management

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

The primary objective of this study is to determine the effectiveness of:
(1) topical intranasal lidocaine (3 mg/kg) and usual care,
(2) intranasal midazolam (0.3 mg/kg) & topical intranasal lidocaine (3 mg/kg) and usual care,
(3) intranasal fentanyl (1.5 mcg/kg) and topical intranasal lidocaine (3 mg/kg) and
(4) usual care, and usual care only for reducing the occurrence of severe distress (score of 7 or more on the FLACC or r-FLACC scale) associated with nasogastric (NG) tube insertion in children aged six months to less than five years (4 years + 364 days).

The registered nurses (RNs) working in the emergency department will administer the intervention medications. All RNs are trained and competent in administering intranasal (IN) medications to paediatric patients. Additionally, the administration of intranasal (IN) medications is a common practice in emergency departments

Dosing, administration and timing of IN medications:
All medication doses are based on the patient's weight.
Each patient will be weighed according to the local policy for paediatric patients.

Intranasal midazolam: The commercially available intravenous preparation of midazolam will be administered intranasally 15 minutes before the procedure at a dose of 0.3 mg/kg to a maximum of 10 mg using site specific supplies (e.g. Mucosal Atomiser DeviceTM) provided for intranasal administration split between nostrils. No alterations to the dose or top-up doses are allowed for study participants.
For this study, an acceptable time deviation for the medication will be: 5 minutes before and 10 minutes after. Therefore, it will be in protocol if the NGT is inserted between 10 minutes and 25 minutes from when IN Midazolam is administered. Outside this window will be a protocol deviation.

Intranasal fentanyl: Fentanyl will be administered intranasally using the commercially available intravenous preparation at a concentration of 100 micrograms / 2 mL using site specific supplies (e.g. Mucosal Atomiser DeviceTM) provided for intranasal administration split between nostrils. For consistency across intervention arms this will be administered 15 minutes before the procedure at a dose of 1.5 micrograms/kg (maximum dose 75 micrograms, noting that most children in the current study will have a considerably lower dose than this). Site-specific devices will be used for intranasal delivery.
For this study, an acceptable time deviation: 5 minutes before and 10 minutes after. Therefore: It will be in protocol if the NGT is inserted between 10 minutes and 25 minutes from when IN Fentanyl is administered. Outside this window will be a protocol deviation.

Topical lidocaine: Lidocaine is commercially available in 10% concentration with a metered dose spray nozzle. Each 100 microlitre metered dose delivers 10 mg of lidocaine. The recommended maximum dose in children is 3 mg/kg. Weight-based doses will be used and will be administered split between nostrils 5 minutes before the procedure. If an odd number of sprays is to be used, then the “extra” spray will be administered to the nostril deemed to most patent (judged by the clinician who is to insert the NG tube).

When administering the intranasal medications to study participants, the dose will be split between both nostrils to avoid medication running down the back of the nasopharynx and being swallowed.

Control: Usual Care
Clinicians will provide usual care based on local policies and clinical practice guidelines. Typically, standard practice is to lubricate the NG tube with water or a water-based lubricant, or, in neonates use their own saliva. Young infants (under 12 months of age) may also be given 2 mL aliquots of 33% sucrose/glucose syrup immediately prior to the insertion attempt. The ‘usual care’ administered to each study participant will be documented on the case report form (CRF). Children randomised to usual care will not be administered any lidocaine, fentanyl, midazolam or other sedation / analgesia.

The trial medications will be prescribed by the treating clinician according to the random allocation for the participant, and this prescription will be documented in the patient’s medical record at each site according to site-specific usual practice.

Hospital medication records will be able to be viewed by the study team to ascertain the dose of intervention medications prescribed, and what was given. All Registered Nurses working in the participating departments are competent and familiar with administering IN medications to children.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Control: usual care
Standard procedures for NG tube insertion will be followed for the usual care group. Clinicians will provide usual care based on local policies and clinical practice guidelines. Typically, standard practice is to lubricate the NG tube with water or a water-based lubricant, or, in neonates use their own saliva. Young infants (under 12 months of age) may also be given 2 mL aliquots of 33% sucrose/glucose syrup immediately prior to the insertion attempt.

Control group

Active

Outcomes

Primary outcome [1]

The primary outcome is severe distress during the first NG tube insertion attempt, where distress is defined as a score more than or equal to 7 on the Face Legs Activity Cry and Consolability (FLACC) or revised (r)-FLACC scale.

Timepoint [1]

Sever distress will be measure during the first NGT insertion attempt. Severe distress during NGT insertion is the point of maximal distress (when the tube is placed in the nostril and fed down to the stomach).

Secondary outcome [1]

Observer (researcher) distress (FLACC/r-FLACC scale) scores:

Timepoint [1]

(a) During administration of fentanyl or midazolam, (b) At time intranasal lidocaine is administered (c) At time of each NGT insertion attempt (to a maximum of 3 attempts) (the point of maximal distress when the tube is placed in the nostril and fed down to the stomach) (d) 5 minutes after NGT is secured/or procedure abandoned (e) 30 minutes post successful NGT insertion (or procedure abandoned) between participants randomised to each intervention with those randomised to usual care.

Secondary outcome [2]

Observer (researcher) documented level of sedation (Observer University of Michigan Sedation Scale (UMSS) scores

Timepoint [2]

a) Lidocaine is administered (b) Time of each NGT insertion attempt (to a maximum of 3 attempts) (c) 5 minutes after NGT is secured (or procedure abandoned) (d) 30 minutes post successful NGT insertion (or procedure abandoned) between those randomised to each intervention with those randomised to usual care.

Secondary outcome [3]

Whether the participant had returned to baseline levels of distress at five minutes after the NGT is fixed in place (or the procedure is abandoned)

Timepoint [3]

five minutes after the NGT is fixed in place (or the procedure is abandoned)

Secondary outcome [4]

Clinician (Either Doctor or Nurse) distress score (11-point NRS)

Timepoint [4]

(a) During administration of intervention (b) During the first attempt to insert the NG tube (c) Five minutes after the NGT is fixed in place (or the procedure is abandoned)

Secondary outcome [5]

Clinician assessment of the ease of NGT insertion

Timepoint [5]

Post NGT insertion (after either successful insertion or procedure aborted).

Secondary outcome [6]

Successful NG tube placements

Timepoint [6]

After either successful NGT insertion, or if failed insertion, procedure aborted.

Secondary outcome [7]

Number of attempts required to achieve successful placement of the NG tube

Timepoint [7]

To be recorded after either successful NGT insertion, or after procedure aborted if not successful. For study purposes, only up to three attempts will be made, however number of attempts will ultimately be decided upon by the clinician responsible for child's care.

Secondary outcome [8]

Clinician estimate of the extent of non-pharmacological measures (restraint) used for procedure overall

Timepoint [8]

Post NGT procedure.

Secondary outcome [9]

Complications associated with the intervention and/or the NG tube insertion procedure

Timepoint [9]

After either successful NGT placement, or if not successful procedure aborted.

Secondary outcome [10]

Clinician (registered nurse or doctor) rated satisfaction with the NG tube insertion procedure and intervention overall

Timepoint [10]

After either successful NGT procedure, or after procedure aborted if not successful.

Secondary outcome [11]

Compare the proportion of children that have recovered from the NGT insertion procedure and interventions received at 30minutes following successful insertion/abandonment of procedure

Timepoint [11]

Baseline (prior to start of procedure) and 30 minutes following successful insertion/abandonment of procedure

Secondary outcome [12]

Cost per participant for NG tube insertion.

Timepoint [12]

Post conclusion of data collection

Secondary outcome [13]

To compare inter-rater reliability of FLACC or r-FLACC scales obtained through assessment of video-recorded NG insertion and those recorded by an observer in the procedure room.

Timepoint [13]

At the time of the first nasogastric tube (NGT) insertion attempt — the FLACC or r-FLACC score will be recorded in real-time by an observer present in the procedure room. Approximately one week following the procedure — the video-recorded NGT insertion will be reviewed by an independent researcher, and the FLACC or r-FLACC score will be re-assessed to enable comparison of inter-rater reliability.

Secondary outcome [14]

Parent / Caregiver rated distress scores (11-point NRS)

Timepoint [14]

- Pre NGT insertion: parent caregiver will be asked to estimate how distressing they think the procedure will be for their child? At time of IN medication administration (Fentanyl / Midazolam / Lidocaine). First NGT insertion attempt. 5 minute after the procedure (after NGT is secured in place or procedure aborted)

Secondary outcome [15]

Parent rated satisfaction with the NG tube insertion procedure and intervention overall

Timepoint [15]

Post successful NGT insertion, or after procedure abandoned if not successful.

Secondary outcome [16]

Time staff commenced preparation of intervention medication. The time at which clinical staff began preparing the intervention medication prior to nasogastric tube insertion.

Timepoint [16]

At time of intervention preparation

Secondary outcome [17]

Time intervention medication was administered: The time at which the intervention medication was administered to the participant.

Timepoint [17]

Prior to nasogastric tube insertion, at time IN medication was administered to the participant.

Secondary outcome [18]

Time administration of intervention medication was completed.

Timepoint [18]

Recorded in case report form by observing nurse

Secondary outcome [19]

Documented dose administered of intervention medication

Timepoint [19]

During intervention preparation or after IN medication administered.

Secondary outcome [20]

Staff roles during administration of intervention medication

Timepoint [20]

During administration of IN medication

Secondary outcome [21]

If any 'usual care' was provided in addition to intervention

Timepoint [21]

Prior to insertion of the NGT, during the intervention stage.

Secondary outcome [22]

Number of staff present during nasogastric tube (NGT) insertion (Total number of staff members in the room at the time of NGT insertion).

Timepoint [22]

During NGT insertion

Secondary outcome [23]

Roles of staff during NGT insertion. (Clinical roles of each staff member involved in NGT insertion (e.g., proceduralist, person restraining, person monitoring patient, others).

Timepoint [23]

During NGT insertion

Secondary outcome [24]

Use of physical restraint during NGT insertion (Whether physical restraint was used during NGT insertion.).

Timepoint [24]

During NGT insertion

Secondary outcome [25]

Number of people required for physical restraint (if applicable)

Timepoint [25]

During NGT insertion

Secondary outcome [26]

If any other forms of restraint used during NGT insertion, e.g. description of any non-physical or alternative restraint strategies used (e.g., comfort holding, distraction, swaddling).

Timepoint [26]

During NGT insertion

Secondary outcome [27]

Time from randomisation to first attempt to insert NG tube

Timepoint [27]

Time randomisation documented. Time of first NGT insertion attempt.

Secondary outcome [28]

Time from randomization to 5 minutes after NGT is inserted and secured (or procedure abandoned)

Timepoint [28]

Time participant randomised to a study group. Documented time the NGT was successfully inserted, or time decision was made to abort the procedure if not successful.

Eligibility

Key inclusion criteria

1. Aged from 6 months to less than 5 years of age (i.e. no older than 4 years and 364 days) receiving care in the emergency department, outpatient clinic, day procedure unit or an inpatient ward setting.
2. Weigh: more than or equal to 7 kg
3. Clinical indication for NG tube insertion

Note:

For the purposes of this study, participant eligibility will be determined using corrected (adjusted) age rather than chronological age. This approach accounts for the developmental differences associated with prematurity and ensures a more accurate assessment of age-dependent outcomes

To standardise this calculation across study sites, we will utilise the NICHD Neonatal Research Network's Adjusted Age Calculator, a reputable and widely used tool in neonatal research .

Minimum age

6 Months

Maximum age

5 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

1. Contraindication to trial medications (midazolam, fentanyl or lidocaine)
2. Acute angle closure glaucoma
3. Known hepatic or renal impairment
4. Known coagulopathy
5. Genetic predisposition to malignant hyperthermia,
6. Severe respiratory distress (respiratory failure needing ventilation, severe acute asthma, severe upper airway obstruction, tracheostomy, impaired cough/ gag).
7. Severe cardiac disease (congestive heart failure, severe pulmonary hypertension, severe arrhythmias)
8. Contraindication to sedation (e.g. patient critically ill, severe respiratory distress)
9. Indication for urgent / emergency NG tube insertion
10. Any other condition that might affect NG tube insertion.
- Altered facial or nasal anatomy
- Facial or nasal trauma
- Other contraindication (please describe)
11. Any concern regarding parent/guardian ability to comply with the study protocol.

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)

Eligible participants will be identified by clinical staff in the emergency department or delegated research staff. Once all inclusion criteria are confirmed and exclusion criteria ruled out, informed consent will be obtained from the parent(s) or legal guardian(s) prior to any trial-specific procedures. Following confirmation of eligibility and consent, participants will be enrolled and randomised using a secure, Centralised web-based randomisation system implemented within REDCap. The randomisation module in REDCap ensures allocation concealment by utilising a pre-programmed randomisation schedule with stratification by site. The allocation sequence is stored within REDCap and is not accessible to investigators, study staff, or monitors. Allocation is revealed by the system only at the point of randomisation, after eligibility and stratification data have been entered and verified. Once a participant is randomised, the allocation is displayed to the clinical team so that the assigned intervention can be implemented without delay.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Participants will be randomised in a 1:1:1:1 ratio to one of three intervention groups or the control group (usual care) using a web-based randomisation procedure. An independent statistician from the Clinical Epidemiology and Biostatistics Unit (CEBU) will generate a randomisation schedule stratified by study site, using block randomisation with variable block sizes. The randomisation schedule will be implemented via the secure randomisation module in REDCap.

Masking / blinding

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Sample size
Our proposed study is designed to address three separate research questions regarding the effectiveness of the 3 interventions compared with usual care within a single trial. The sample size calculation for the primary outcome (severe distress during first insertion attempt) was based on distress scores during NG tube insertion from previous studies. In these studies, we found that 94% of children receiving usual care have FLACC scores of 7 or higher. A reduction by 15% in the proportion of children with severe distress (score greater than or equal to 7) with each of the proposed study interventions compared to usual care (i.e. from 94% to 79%), is considered clinically significant after consultation with front-line clinical staff working across the participating Emergency Departments.
To achieve a reduction by 15% in the proportion of children with severe distress (score greater than or equal to 7) with each of the proposed study interventions compared to usual care (i.e. from 94% to 79%) with 85% power, 105 children will be required in each group (based on a two-sided Chi-squared test with a continuity correction and alpha=0.05). To allow for 10% loss to follow-up, we aim to recruit a total of 468 children across the 4 study arms, with 117 children in each.
Statistical analysis
Data will be analysed following the intention-to-treat principle, using a treatment policy strategy to handle all intercurrent events. Demographic and baseline data will be summarised using standard descriptive statistics by intervention group. The primary outcome of severe distress during the first NG tube insertion will be presented as a proportion in each group, and a comparison between each of the intervention groups and control will be presented as a difference in proportions, estimated using binomial regression adjusted for site, presented with a 95% confidence interval and p-value. Other secondary outcomes will be summarised by group, using means and standard deviations (normally-distributed continuous outcomes), median and IQR (continuous outcomes following a non-parametric distribution) of frequencies and proportions (binary outcomes) with comparisons between each of the intervention groups and the control group presented as mean differences or differences or difference between the medians, or differences in proportions estimated using linear, quantile and binomial regression as appropriate, adjusted by site. If the percentage of missing data on the primary outcome is greater than 5% we will consider the potential mechanism behind the missing data and use this to guide the analytic approach for example using multiple imputation techniques if warranted.

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

4/08/2025

Actual

Date of last participant enrolment

Anticipated

31/07/2028

Actual

Date of last data collection

Anticipated

7/08/2028

Actual

Sample size

Target

468

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD,SA,WA,VIC

Recruitment hospital [1]

Gold Coast University Hospital - Southport

Recruitment hospital [2]

Monash Children’s Hospital - Clayton

Recruitment hospital [3]

Perth Children's Hospital - Nedlands

Recruitment hospital [4]

Queensland Children's Hospital - South Brisbane

Recruitment hospital [5]

The Royal Childrens Hospital - Parkville

Recruitment hospital [6]

Womens and Childrens Hospital - North Adelaide

Recruitment hospital [7]

Fiona Stanley Hospital - Murdoch

Recruitment postcode(s) [1]

4215 - Southport

Recruitment postcode(s) [2]

3168 - Clayton

Recruitment postcode(s) [3]

6009 - Nedlands

Recruitment postcode(s) [4]

4101 - South Brisbane

Recruitment postcode(s) [5]

3052 - Parkville

Recruitment postcode(s) [6]

5006 - North Adelaide

Recruitment postcode(s) [7]

6150 - Murdoch

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Auckland

Funding & Sponsors

Funding source category [1]

Government body

Name [1]

Medical Research Future Fund - Australian Government Department of Health, Disability and Ageing

Address [1]

Country [1]

Australia

Primary sponsor type

University

Name

Monash University

Address

Country

Australia

Secondary sponsor category [1]

Individual

Name [1]

Professor Simon Craig - Monash University, Melbourne, VIC.

Address [1]

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Monash Health Human Research Ethics Committee A

Ethics committee address [1]

https://monashhealth.org/research/resources/resource-library/

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

03/10/2024

Approval date [1]

17/04/2025

Ethics approval number [1]

Summary

Brief summary

This study aims to determine the efficacy of 1) topical (applied to the nasal mucosa) lidocaine and usual care, 2) intranasal midazolam plus topical lidocaine and usual care and 3) intranasal fentanyl plus topical lidocaine and usual care compared to 4) usual care for reducing the occurrence of severe distress experienced by children aged 6 months to less than 5 years (i.e. 4 years and 364 days) associated with NG tube insertion.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Simon Craig

Address

Monash University Clayton Campus, Wellington Rd, Clayton VIC 3800

Country

Australia

Phone

+61 03 9594 2707

Fax

[email protected]

Contact person for public queries

Name

Simon Craig

Address

Monash University Clayton Campus, Wellington Rd, Clayton VIC 3800

Country

Australia

Phone

+61 03 9594 2707

Fax

[email protected]

Contact person for scientific queries

Name

Simon Craig

Address

Monash University Clayton Campus, Wellington Rd, Clayton VIC 3800

Country

Australia

Phone

+61 03 9594 2707

Fax

[email protected]

Data sharing statement

Will the study consider sharing individual participant data?

Yes

Will there be any conditions when requesting access to individual participant data?

Persons/groups eligible to request access:
• Researchers
Conditions for requesting access:
• Yes, conditions apply:
• Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
• Requires a scientifically sound proposal or protocol
• Requires approval by an ethics committee
• Requires a data sharing agreement between data requester and trial custodian or sponsor

What individual participant data might be shared?

• All de-identified individual participant data

What types of analyses could be done with individual participant data?

• Systematic reviews and meta-analyses
• Studies exploring new research questions
• Health economic analyses
• Studies testing whether findings can be repeated or confirmed

When can requests for individual participant data be made (start and end dates)?

From:
After publication of main results
To:
No end date

Where can requests to access individual participant data be made, or data be obtained directly?

• Email of trial custodian, sponsor or committee: [email protected]

Are there extra considerations when requesting access to individual participant data?

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically