Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT06100159 |
| Other study ID # |
REG-131-2015 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 20, 2017 |
| Est. completion date |
August 30, 2022 |
Study information
| Verified date |
October 2023 |
| Source |
Zealand University Hospital |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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 and/or
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 36.000 TTI are performed on children in Denmark. The annual incidence is
108 : 1.000 for children between 0-3 years of age and 35 : 1.000 in children between 0-15
years of age. In comparison, the annual incidence is lower than 10 : 1.000 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 children's 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 children's and their caregiver's QoL before and after TTI through validated
questionnaires and measurements of the children's 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 caregiver's 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 child's 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 caregiver's assessment of changes
in the child's 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 children's 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 children's 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 tube/grommet. 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 31.12.2025. All excess fluids will be destroyed hereafter.
Statistical considerations The following mathematical assumptions were made to calculate the
sample size. Estimated awakenings/periods of high activity during sleep before TTI: 6
episodes per night. Estimated reduced awakenings/periods of high activity during sleep = 20%
meaning 6 x 0,8 = 4,8 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 0,95 = 5,70/4 = 1,425. Type 1 error (α) is
set per standard 0,05. Type 2 error (β) is set per standard 0,2 and power is set to 0,8. 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 1,2 = 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 child's 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 guideline's section 4.2.1.1. The trial has also been approved by The
Danish Data Protection Agency "Datatilsynet" and is registered on clinicaltrials.gov.
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,
Ph.d, 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 Tingsgaard's 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.
