Clinical Trial Results:
Observational study of lidocaine levels in children after airway topicalisation during direct laryngotracheobronchosopy (DLTB).
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Summary
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EudraCT number |
2014-005207-25 |
Trial protocol |
GB |
Global end of trial date |
10 Jul 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
05 Apr 2020
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First version publication date |
05 Apr 2020
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
R03818
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Other trial identifiers |
UK Research Ethics Service: 16/NW/0004 | ||
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Sponsors
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Sponsor organisation name |
Manchester University NHS Foundation Trust
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Sponsor organisation address |
Oxford Road, Manchester, United Kingdom,
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Public contact |
Dr Lynne Webster, Manchester University NHS Foundation Trust, +44 01612764125, research.sponsor@mft.nhs.uk
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Scientific contact |
Dr Lynne Webster, Manchester University NHS Foundation Trust, +44 01612764125, research.sponsor@mft.nhs.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 Jul 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
10 Jul 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
10 Jul 2018
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To identify the peak blood levels of lidocaine in children undergoing an endoscopic examination of their airways under anaesthesia. The local anaesthetic lidocaine, is routinely applied to the airway during this procedure as part of the anaesthetic technique.
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Protection of trial subjects |
The potential risks of insertion of a supplementary intravenous cannula include bruising, localized skin infection, and allergy to the antiseptic solution used (chlorhexidine gluconate 2% in ethanol 70%), or to the cannula dressing. However, these final two risks are not additional to standard, as all children are routinely cannulated during DLTB. The 0.9% saline flush used for cannula patency poses negligible risk, even in the case of extravasation. The blood samples would total 5.5ml of venous blood, and thus do not pose a risk of anaemia to our participants. In order to minimise any risk, this procedure will be performed by an senior anaesthetic registar or consultant anaesthetist in accordance with trust guidelines.
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Background therapy |
In our current practice at Royal Manchester Children’s Hospital, general anaesthesia for direct laryngotracheobronchoscopy (DLTB) in children is carried out using a spontaneously breathing technique, and is routinely supplemented by lidocaine applied topically to the airway. This is applied to both the supraglottis and subglottis. The method of application is by a mucosal atomisation device. Varying doses, between 3 to 5mg per kg, are being used. The study does not involve any change to the routine clinical care given to children undergoing DTLB. All children undergoing this procedure will receive lidocaine as described above, therefore the risk associated with the investigational medicinal product lidocaine in this clinical trial is no greater than the risk to which participants would be exposed were they to undergo DTLB at this hospital and not enter the trial. The trial differs from routine care only in the measurement of lidocaine levels: a supplementary intravenous cannula will be inserted during general anaesthesia, in order to obtain four blood samples for lidocaine plasma levels. This off-label use of lidocaine is established practice in our and other hospitals. | ||
Evidence for comparator |
The population from which participants will be selected are children undergoing elective direct laryngotracheobronchosopy as part of their clinical management by the ENT surgeons in Royal Manchester Children's Hospital. There is no change to their primary procedure or anaesthetic technique. The only additional procedure they will undergo as part of the study is the insertion of a supplementary intravenous cannula during general anaesthesia, in order to obtain four blood samples for lidocaine plasma levels. | ||
Actual start date of recruitment |
01 Nov 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 50
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Worldwide total number of subjects |
50
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EEA total number of subjects |
50
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
30
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Children (2-11 years) |
20
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The population from which participants will be selected are children undergoing elective direct laryngotracheobronchosopy as part of their clinical management by the ENT surgeons in RMCH. UK only study, recruitment period 18/01/2017 to 17/01/2018. | ||||||
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Pre-assignment
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Screening details |
The population from which participants will be selected are children undergoing elective direct laryngotracheobronchosopy as part of their clinical management by the ENT surgeons in Royal Manchester Children's Hospital. | ||||||
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Period 1
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Period 1 title |
Baseline (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Whole cohort | ||||||
Arm description |
- | ||||||
Arm type |
Whole cohort | ||||||
Investigational medicinal product name |
Lidocaine Hydrochloride Injection BP 2% w/v
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Investigational medicinal product code |
01502/0036
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Other name |
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Endotracheopulmonary use
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Dosage and administration details |
3-5mg/kg total was the maximum dose
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Baseline characteristics reporting groups
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Reporting group title |
Baseline
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Whole cohort
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Whole cohort
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End points reporting groups
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Reporting group title |
Whole cohort
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Reporting group description |
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Subject analysis set title |
Whole cohort
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Whole cohort
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End point title |
Peak plasma [1] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Full study
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Linear regression models were used to assess the relationship between peak plasma concentration and variables of age, weight, volume and dose. These do not compare groups as this is a single arm trial and do not fit in this system. There is a significant quadratic relationship between peak plasma level and age (p=0.00973). There is a significant quadratic relationship between volume of local anaesthetic utilised and peak plasma levels (p=0.0352). |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to peak plasma | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Whole study
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| No statistical analyses for this end point | |||||||||
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End point title |
Plasma over toxicity level | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Whole study
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| No statistical analyses for this end point | |||||||||||
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End point title |
Adverse Effect | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Whole Study
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| No statistical analyses for this end point | |||||||||||
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End point title |
Fluid bolus | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Whole study
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| No statistical analyses for this end point | |||||||||||
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End point title |
Signs of LA toxicity | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Whole study
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| No statistical analyses for this end point | |||||||||||
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End point title |
Second cannula removed | ||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Whole Study
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| No statistical analyses for this end point | |||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
All adverse events and adverse reactions up to 24hours after surgery were to be recorded on the Adverse Events Recording form and will be reviewed by the sponsor at routine study monitoring visits.
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Assessment type |
Non-systematic | ||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
Whole cohort
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||
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| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: There were no adverse events within this trial. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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06 Dec 2016 |
Substantial amendment 1:
1. Change to laboratory providing analysis for primary endpoint.
2. Addition of further protocol authors. |
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01 Mar 2017 |
Substantial amendment 2:
1. Change to protocol to allow initial approach to the parents of potential trial participants by telephone and letter.
2. Extension to study to July 2018 (planned date of last participant last visit).
3. Minor typographical and administrative changes to protocol.
4. Addition of new covering letter to send with study information leaflet to potential recruits. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None. | |||
