Ignite Creation Date:
2024-05-06 @ 7:43 PM
Last Modification Date:
2024-10-26 @ 3:11 PM
Study NCT ID:
NCT06100159
Status:
COMPLETED
Last Update Posted:
2023-10-25
First Post:
2017-02-17
Brief Title:
Short-term Effects of Ventilation Tubes in Children With Chronic Otitis Media With Effusion
Sponsor:
Zealand University Hospital
Organization:
Zealand University Hospital
Study Overview
Official Title:
Short-term Effects of Ventilation Tubes in Children With Chronic Otitis Media With Effusion Treated in ENT Private Practice a Randomised Controlled Trial
Status:
COMPLETED
Status Verified Date:
2023-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this clinical randomized trial is to compare the sleeping patterns and quality of life of children with chronic otitis media with effusion OME with or without tympanic tubes insertion The main questions it aims to answer are
Does tympanic tube insertion have an effect on sleep quality in children with chronic OME
Does tympanic tube insertion improve the quality of life for the children with chronic OME and their caregivers
Participants will have their movements during sleep and number of awakenings measured by an accelerometer placed on their wrist for 7 nights before and after tympanic tube insertion Their caregivers will answer questionnaires regarding quality of life on behalf of the child Researchers will compare with a control group of children who also is diagnosed with chronic OME They will also have their sleep monitored for 7 nights and their caregivers will complete quality of life questionnaires but the will not receive a tympanic tube However the control group will be reassessed a month after baseline and if they still qualify for tympanic tube insertion they will undergo the same routine as the intervention group
Does tympanic tube insertion have an effect on sleep quality in children with chronic OME
Does tympanic tube insertion improve the quality of life for the children with chronic OME and their caregivers
Participants will have their movements during sleep and number of awakenings measured by an accelerometer placed on their wrist for 7 nights before and after tympanic tube insertion Their caregivers will answer questionnaires regarding quality of life on behalf of the child Researchers will compare with a control group of children who also is diagnosed with chronic OME They will also have their sleep monitored for 7 nights and their caregivers will complete quality of life questionnaires but the will not receive a tympanic tube However the control group will be reassessed a month after baseline and if they still qualify for tympanic tube insertion they will undergo the same routine as the intervention group
Detailed Description:
Statement of intent
Background Otitis media with effusion OME is a common condition in the population of young children in Denmark Sixty percent of the Danish children will experience at least one episode of OME or acute otitis media before they are 7 years old
OME is a condition defined by non-purulent inflammation of the middle ear with serous andor mucinous secretion why it is also known as serous otitis media The diagnosis is most often made by a general practitioner or an ear nose-throat ENT specialist by otoscopy and measuring the middle ear pressure with a tympanometer After a period of 3 months with persistent fluid in the middle ear the treatment is usually insertion of a tympanostomy tube also called a grommet in the tympanic membrane OME may be accompanied by varying degrees of non-infectious symptoms including earaches hearing loss and reduced quality of life
Tympanostomy tube insertions TTI are also performed in children with recurring acute otitis media The Danish Health Authority Sundhedsstyrelsen has collaborated with multiple Danish ENT specialists and published a peer reviewed National Clinical Guideline NCG regarding TTI
Denmark has the highest rate of tympanostomy tube insertion TTI in children in the world Every year around 36000 TTI are performed on children in Denmark The annual incidence is 108 1000 for children between 0-3 years of age and 35 1000 in children between 0-15 years of age In comparison the annual incidence is lower than 10 1000 in United Kingdom USA and Canada Recent studies by DØNHOF Danish Ear- Nose and Throat Specialists Organization Research Group have shown that the vast majority of TTI procedures are conducted according to the National Clinical Guidelines NCG
However this major difference in procedure ratio between countries raises questions Is the procedure performed too often in Denmark or not often enough in other countries Do more children suffer from OME in Denmark compared to other parts of the world Large and thorough studies have been made to assess the impact of TTI on hearing speech and cognitive development of children with OME So far has no significant long-term benefits been found
High quality studies on quality of life QoL in children with OME and their caregivers are few Questionnaire studies on this subject find that caregivers generally report improved QoL for their children after TTI In particular the caregivers describe a poor and broken-up sleep pattern when their child is diagnosed with OME They also report that the sleep pattern significantly improves after TTI which increases QoL for the child as well as their caregivers These QoL questionnaire studies have not been randomized and are at high risk of selection bias where caregivers may prefer TTI
Even the most recent nationally published studies have pointed out the need for an objective randomized evaluation of the effect of TTI This has not been possible until recently
New FDA-approved technology the Actigraph gt3x 3-axis accelerometer makes it possible to objectively register movement during sleep awakenings and total amount of sleep and thereby evaluate the quality of the childrens sleep also called sleep efficiency
It is internationally discussed how long an observation period for OME is needed before treatment with TTI is indicated In Denmark and many other countries the period of observation is set to 3 months An observational patient reported outcome PRO study by caregivers to children offered TTI from 26 ENT clinics spread across Denmark showed that 91 of TTI procedures were conducted adherent to the NCG However this was without data on hearing loss or tympanometry OME is a condition that can be resolved spontaneously so if you apply a longer observation period it is possible that fewer children would undergo surgery Therefore there is a need to study if the current NCG is of benefit for the children and their families compared to a longer observation period
Objectives
1 Evaluate the sleep efficiency of children with OME before and after TTI by state-of the-art objective measurement using the Actigraph gt3x accelerometer and a validated questionnaire The decision to perform TTI will be in accordance with the NCG
2 Evaluate the childrens and their caregivers QoL before and after TTI through validated questionnaires and measurements of the childrens sleep pattern
3 Evaluate if the currently recommended observation period of 3 months is sufficient or if 4 months observation would be more appropriate
Hypotheses
1 TTI in children with OME induces better sleep patterns and better sleep efficiency
2 The children and their caregivers QoL is improved by TTI
3 The current observation period of 3 months before deciding on TTI is satisfactory
Methods Study design The study design is a randomized controlled trial The person analyzing the sleep efficiency will be blinded to the randomization not knowing if the data is coming from the intervention or the control group For ethical and practical reasons the caregivers and children cannot be blinded to the randomization
The majority of TTI surgery in Denmark is performed by private practicing ear-nose-throat ENT specialists as a part of the public health facilities The ENT specialist will be responsible for including the children when they meet the requirements of the NCG for the TTI procedure and screen for the exclusion criteria The children must be diagnosed with OME for three consecutive months and the caregivers suspect that their childs hearing is impaired If the child matches the inclusion criteria they and their caregivers will be informed about the trial verbally and in writing before they are asked to join The children are included longitudinally and will be randomized into the intervention or the control group
The intervention group will be scheduled for TTI performed by the ENT specialist as per NCG with sleep registration 7 nights before and after the procedure The control group will go through a 7-night sleep registration at the inclusion point and then an additional month of observation Afterwards the children in the control group will be reassessed by the ENT specialist If they still meet the inclusion criteria for TTI they will be offered the procedure and will be included in the intervention group For both groups the ENT specialist must fill out the provided questionnaires documenting the caregiver reported symptoms before TTI and the objective findings including otomicroscopy and tympanometry before and after the TTI The impact of TTI on hearing has been thoroughly investigated and is therefore not an end outcome in this study However questions regarding the caregivers assessment of changes in the childs hearing is included in the questionnaires The QoL questionnaires for the caregivers are to be answered at time of inclusion and depending on the group again after TTI or again after 1 month of observation
The caregivers are asked to write down the time their child was put to bed if they provided their child with paracetamol at any time and estimate how long their child slept each night There will also be an option to comment on if there were any competing illnesses in the period of sleep registration
To register the childrens activity in their sleep and thereby their sleeping pattern and efficiency they will be fitted with a 3-axis accelerometer called the Actigraph gt3x which in shape and size resembles a wristwatch It is a noninvasive monitor which provides precise and validated data about movement during sleep It is an FDA approved medico-technical equipment and state-of-the-art for measuring activity in children The children will wear the watch on their wrist at nighttime only
The childrens sleep will be registered as close to the time of inclusion as possible and exactly the 7 nights before the TTI and the 7 nights immediately after the procedure which means 14 nights in total for the intervention group
In the control group their sleep will be monitored 7 nights at the time of the inclusion After 1 month of observation they will be reassessed by the ENT specialist If they still meet the criteria of the NCG they too will be offered TTI If they accept they will join the intervention group with the measurements of activity during sleep 7 nights before and 7 nights after TTI and the caregivers will again fill out the questionnaires This sum up to a maximum of 21 nights with measurement in total for the children in the control group Grommets of the type Donaldson will be used in all TTI procedures
Research biobank In relation to this project there will be established a biobank During a TTI procedure the fluid in the middle ear is removed by suction to minimize risk of inflammation around and blockage of the ear tubegrommet This fluid is normally discarded but during this project the fluid will be kept with the intention of later analysis for microbiome
The analysis will include examination for bacteria and virus remnants 16 s rRNA and 16 s rDNA The fluid which is comprised of about 2 mL per ear is saved in an -80 degree Celsius freezer in the safe facilities
The purpose of the biobank is to store the fluid until all samples are collected and the analysis tools are fully financed
The biobank will cease to exist 31122025 All excess fluids will be destroyed hereafter
Statistical considerations The following mathematical assumptions were made to calculate the sample size Estimated awakeningsperiods of high activity during sleep before TTI 6 episodes per night Estimated reduced awakeningsperiods of high activity during sleep 20 meaning 6 x 08 48 episodes per night after TTI The estimated standard deviation for the normal child population 2-8 episodes per night
The calculated standard deviation equals 8-2 6 x 095 5704 1425 Type 1 error α is set per standard 005 Type 2 error β is set per standard 02 and power is set to 08 The calculated sample size for each group equals 24 children meaning 48 children in total
Finally a dropout rate of 20 is estimated and add that to our total 48 x 12 58 children Investigators has chosen to round that up to 60
The sample size is as follows 30 children in the control group and 30 children in the intervention group Keeping in mind that the 30 children in the control group can after the 1 month of observation also be included in the intervention group if they still meet the NCG criteria for TTI That means the potential of 60 children in the intervention group
Scientific and socioeconomic perspectives Even the most up-to date national and international studies and reviews request randomized controlled studies investigating the effects of TTI This randomized controlled study will provide completely new knowledge no matter the outcome It is the first to measure sleep efficiency in relation to OME If it proves a significant and objectively measured improvement in sleep after TTI and it correlates to the answers in the QoL questionnaires it could be an international game changer with benefits for the children suffering from OME and a support to the clinical practice in Denmark A good sleep is such an important factor in a childs ability to acquire new knowledge and for their caregivers to be able to go to work and function at work Therefore it could lead to new international clinical guidelines for TTI and bring better QoL to the children with OME and their families If our study does not show a significant effect that could give evidence to suggest a reduction in TTI among children in Denmark
Side effects and risks to participants Partaking in this study will not cause any health risks to the participants compared to children that do not partake in the study There are no documented side effects complications or disadvantages to waiting an additional month before getting TTI 10 The overall risk associated with TTI are mainly the risks of general anesthesia and a 1-6 risk of a persisting perforation of the tympanic membrane that could require surgical treatment There are no risks involved in the usage or wearing of the Actigraph gt3x accelerometer which is FDA approved The Actigraph gt3x accelerometer has previously been used in numerous studies measuring activity of children
Scientific ethical considerations This trial has been approved by the Danish Committee for Scientific Research Nationale Videnskabsetiske Komité REG-131-2015 and meet the criteria of category C in their guidelines section 4211 The trial has also been approved by The Danish Data Protection Agency Datatilsynet and is registered on clinicaltrialsgov Information about the participants is protected by The General Data Protection Regulation GDPR
Practical Feasibility This study was initiated by Principal investigator Preben Homøe MD Phd DMSc and professor at the Department of Otorhinolaryngology and Maxillofacial Surgery Zealand University Hospital together with field researcher and colleague Trine Nybo Ranneries MD Two ENT specialists with each their own private ENT clinic Peter Kofoed Tingsgaard MD PhD and Christian Hamilton Heidemann MD PhD have participated from the beginning of the planning of the study and acted as study sites with inclusion of patients gathering of consent questionnaires and performing the TTI and controls
Trine N Ranneries is currently a specialist registrar with 1 year remaining in training to become an ENT specialist and has been amanuensis in Peter Tingsgaards practice
The inclusion of participants and collection of data was started with funding from Foreningen af Danske Speciallægers forskningsfond The Research Fond for the Danish Private Practitioners to acquire the wActisleep watches and software
At present time all 60 participants have been included and the follow-up period has been completed
Background Otitis media with effusion OME is a common condition in the population of young children in Denmark Sixty percent of the Danish children will experience at least one episode of OME or acute otitis media before they are 7 years old
OME is a condition defined by non-purulent inflammation of the middle ear with serous andor mucinous secretion why it is also known as serous otitis media The diagnosis is most often made by a general practitioner or an ear nose-throat ENT specialist by otoscopy and measuring the middle ear pressure with a tympanometer After a period of 3 months with persistent fluid in the middle ear the treatment is usually insertion of a tympanostomy tube also called a grommet in the tympanic membrane OME may be accompanied by varying degrees of non-infectious symptoms including earaches hearing loss and reduced quality of life
Tympanostomy tube insertions TTI are also performed in children with recurring acute otitis media The Danish Health Authority Sundhedsstyrelsen has collaborated with multiple Danish ENT specialists and published a peer reviewed National Clinical Guideline NCG regarding TTI
Denmark has the highest rate of tympanostomy tube insertion TTI in children in the world Every year around 36000 TTI are performed on children in Denmark The annual incidence is 108 1000 for children between 0-3 years of age and 35 1000 in children between 0-15 years of age In comparison the annual incidence is lower than 10 1000 in United Kingdom USA and Canada Recent studies by DØNHOF Danish Ear- Nose and Throat Specialists Organization Research Group have shown that the vast majority of TTI procedures are conducted according to the National Clinical Guidelines NCG
However this major difference in procedure ratio between countries raises questions Is the procedure performed too often in Denmark or not often enough in other countries Do more children suffer from OME in Denmark compared to other parts of the world Large and thorough studies have been made to assess the impact of TTI on hearing speech and cognitive development of children with OME So far has no significant long-term benefits been found
High quality studies on quality of life QoL in children with OME and their caregivers are few Questionnaire studies on this subject find that caregivers generally report improved QoL for their children after TTI In particular the caregivers describe a poor and broken-up sleep pattern when their child is diagnosed with OME They also report that the sleep pattern significantly improves after TTI which increases QoL for the child as well as their caregivers These QoL questionnaire studies have not been randomized and are at high risk of selection bias where caregivers may prefer TTI
Even the most recent nationally published studies have pointed out the need for an objective randomized evaluation of the effect of TTI This has not been possible until recently
New FDA-approved technology the Actigraph gt3x 3-axis accelerometer makes it possible to objectively register movement during sleep awakenings and total amount of sleep and thereby evaluate the quality of the childrens sleep also called sleep efficiency
It is internationally discussed how long an observation period for OME is needed before treatment with TTI is indicated In Denmark and many other countries the period of observation is set to 3 months An observational patient reported outcome PRO study by caregivers to children offered TTI from 26 ENT clinics spread across Denmark showed that 91 of TTI procedures were conducted adherent to the NCG However this was without data on hearing loss or tympanometry OME is a condition that can be resolved spontaneously so if you apply a longer observation period it is possible that fewer children would undergo surgery Therefore there is a need to study if the current NCG is of benefit for the children and their families compared to a longer observation period
Objectives
1 Evaluate the sleep efficiency of children with OME before and after TTI by state-of the-art objective measurement using the Actigraph gt3x accelerometer and a validated questionnaire The decision to perform TTI will be in accordance with the NCG
2 Evaluate the childrens and their caregivers QoL before and after TTI through validated questionnaires and measurements of the childrens sleep pattern
3 Evaluate if the currently recommended observation period of 3 months is sufficient or if 4 months observation would be more appropriate
Hypotheses
1 TTI in children with OME induces better sleep patterns and better sleep efficiency
2 The children and their caregivers QoL is improved by TTI
3 The current observation period of 3 months before deciding on TTI is satisfactory
Methods Study design The study design is a randomized controlled trial The person analyzing the sleep efficiency will be blinded to the randomization not knowing if the data is coming from the intervention or the control group For ethical and practical reasons the caregivers and children cannot be blinded to the randomization
The majority of TTI surgery in Denmark is performed by private practicing ear-nose-throat ENT specialists as a part of the public health facilities The ENT specialist will be responsible for including the children when they meet the requirements of the NCG for the TTI procedure and screen for the exclusion criteria The children must be diagnosed with OME for three consecutive months and the caregivers suspect that their childs hearing is impaired If the child matches the inclusion criteria they and their caregivers will be informed about the trial verbally and in writing before they are asked to join The children are included longitudinally and will be randomized into the intervention or the control group
The intervention group will be scheduled for TTI performed by the ENT specialist as per NCG with sleep registration 7 nights before and after the procedure The control group will go through a 7-night sleep registration at the inclusion point and then an additional month of observation Afterwards the children in the control group will be reassessed by the ENT specialist If they still meet the inclusion criteria for TTI they will be offered the procedure and will be included in the intervention group For both groups the ENT specialist must fill out the provided questionnaires documenting the caregiver reported symptoms before TTI and the objective findings including otomicroscopy and tympanometry before and after the TTI The impact of TTI on hearing has been thoroughly investigated and is therefore not an end outcome in this study However questions regarding the caregivers assessment of changes in the childs hearing is included in the questionnaires The QoL questionnaires for the caregivers are to be answered at time of inclusion and depending on the group again after TTI or again after 1 month of observation
The caregivers are asked to write down the time their child was put to bed if they provided their child with paracetamol at any time and estimate how long their child slept each night There will also be an option to comment on if there were any competing illnesses in the period of sleep registration
To register the childrens activity in their sleep and thereby their sleeping pattern and efficiency they will be fitted with a 3-axis accelerometer called the Actigraph gt3x which in shape and size resembles a wristwatch It is a noninvasive monitor which provides precise and validated data about movement during sleep It is an FDA approved medico-technical equipment and state-of-the-art for measuring activity in children The children will wear the watch on their wrist at nighttime only
The childrens sleep will be registered as close to the time of inclusion as possible and exactly the 7 nights before the TTI and the 7 nights immediately after the procedure which means 14 nights in total for the intervention group
In the control group their sleep will be monitored 7 nights at the time of the inclusion After 1 month of observation they will be reassessed by the ENT specialist If they still meet the criteria of the NCG they too will be offered TTI If they accept they will join the intervention group with the measurements of activity during sleep 7 nights before and 7 nights after TTI and the caregivers will again fill out the questionnaires This sum up to a maximum of 21 nights with measurement in total for the children in the control group Grommets of the type Donaldson will be used in all TTI procedures
Research biobank In relation to this project there will be established a biobank During a TTI procedure the fluid in the middle ear is removed by suction to minimize risk of inflammation around and blockage of the ear tubegrommet This fluid is normally discarded but during this project the fluid will be kept with the intention of later analysis for microbiome
The analysis will include examination for bacteria and virus remnants 16 s rRNA and 16 s rDNA The fluid which is comprised of about 2 mL per ear is saved in an -80 degree Celsius freezer in the safe facilities
The purpose of the biobank is to store the fluid until all samples are collected and the analysis tools are fully financed
The biobank will cease to exist 31122025 All excess fluids will be destroyed hereafter
Statistical considerations The following mathematical assumptions were made to calculate the sample size Estimated awakeningsperiods of high activity during sleep before TTI 6 episodes per night Estimated reduced awakeningsperiods of high activity during sleep 20 meaning 6 x 08 48 episodes per night after TTI The estimated standard deviation for the normal child population 2-8 episodes per night
The calculated standard deviation equals 8-2 6 x 095 5704 1425 Type 1 error α is set per standard 005 Type 2 error β is set per standard 02 and power is set to 08 The calculated sample size for each group equals 24 children meaning 48 children in total
Finally a dropout rate of 20 is estimated and add that to our total 48 x 12 58 children Investigators has chosen to round that up to 60
The sample size is as follows 30 children in the control group and 30 children in the intervention group Keeping in mind that the 30 children in the control group can after the 1 month of observation also be included in the intervention group if they still meet the NCG criteria for TTI That means the potential of 60 children in the intervention group
Scientific and socioeconomic perspectives Even the most up-to date national and international studies and reviews request randomized controlled studies investigating the effects of TTI This randomized controlled study will provide completely new knowledge no matter the outcome It is the first to measure sleep efficiency in relation to OME If it proves a significant and objectively measured improvement in sleep after TTI and it correlates to the answers in the QoL questionnaires it could be an international game changer with benefits for the children suffering from OME and a support to the clinical practice in Denmark A good sleep is such an important factor in a childs ability to acquire new knowledge and for their caregivers to be able to go to work and function at work Therefore it could lead to new international clinical guidelines for TTI and bring better QoL to the children with OME and their families If our study does not show a significant effect that could give evidence to suggest a reduction in TTI among children in Denmark
Side effects and risks to participants Partaking in this study will not cause any health risks to the participants compared to children that do not partake in the study There are no documented side effects complications or disadvantages to waiting an additional month before getting TTI 10 The overall risk associated with TTI are mainly the risks of general anesthesia and a 1-6 risk of a persisting perforation of the tympanic membrane that could require surgical treatment There are no risks involved in the usage or wearing of the Actigraph gt3x accelerometer which is FDA approved The Actigraph gt3x accelerometer has previously been used in numerous studies measuring activity of children
Scientific ethical considerations This trial has been approved by the Danish Committee for Scientific Research Nationale Videnskabsetiske Komité REG-131-2015 and meet the criteria of category C in their guidelines section 4211 The trial has also been approved by The Danish Data Protection Agency Datatilsynet and is registered on clinicaltrialsgov Information about the participants is protected by The General Data Protection Regulation GDPR
Practical Feasibility This study was initiated by Principal investigator Preben Homøe MD Phd DMSc and professor at the Department of Otorhinolaryngology and Maxillofacial Surgery Zealand University Hospital together with field researcher and colleague Trine Nybo Ranneries MD Two ENT specialists with each their own private ENT clinic Peter Kofoed Tingsgaard MD PhD and Christian Hamilton Heidemann MD PhD have participated from the beginning of the planning of the study and acted as study sites with inclusion of patients gathering of consent questionnaires and performing the TTI and controls
Trine N Ranneries is currently a specialist registrar with 1 year remaining in training to become an ENT specialist and has been amanuensis in Peter Tingsgaards practice
The inclusion of participants and collection of data was started with funding from Foreningen af Danske Speciallægers forskningsfond The Research Fond for the Danish Private Practitioners to acquire the wActisleep watches and software
At present time all 60 participants have been included and the follow-up period has been completed
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None