Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04478201 |
| Other study ID # |
B00785 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 28, 2022 |
| Est. completion date |
September 2024 |
Study information
| Verified date |
August 2023 |
| Source |
Manchester University NHS Foundation Trust |
| Contact |
Ola Metryka |
| Phone |
+44 (0)161 701 3543 |
| Email |
slumbrs[@]mft.nhs.uk |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The craniofacial abnormalities found in infants and children with cleft palate (CP) lead to
increased risk of obstructive sleep apnoea (OSA). In children and adults sleep position is
known to influence the patency of the airway during sleep. Altering sleep position in infants
with CP may offer a 'low-cost, high impact' intervention to limit the negative impacts of OSA
on child development.
Children with CP are at increased risk of impairment in learning, memory and cognition, with
OSA representing an additional risk to cognitive development. Infants with CP are at risk of
poor weight gain and 'failure to thrive', which can be further exacerbated by co-existing
OSA.
The design and conduct of the proposed randomised controlled trial will benefit from lessons
learned from both the feasibility and other previous studies. Investigators demonstrated that
existing advice given about sleep position varied significantly with some centres
recommending back-lying and others side-lying. Sample size calculations were based on this
multi-source data. Parents in the feasibility study knew that sleep position advice for
infants with CP changes regularly. They understood why not adhering to 'national guidance'
(DoH 2009, Back to Sleep) could be necessary as their infants are "different to normal
infants".
How will this study benefit infants with cleft palate and their parents? The proposed study
will eliminate the current uncertainty and variability in advice provided to parents of
infants with CP, whilst potentially limiting the negative impact of OSA on development. This
work has been prioritised and received unanimous support from Cleft Lip and Palate
Association (CLAPA), Craniofacial Society Great Britain and Ireland (CFSGBI) and Clinical
Nurse Specialists. Aim.To determine the clinical effectiveness in infants with CP of
side-lying as compared to back-lying sleep positioning in reducing oxygen desaturation
resulting from OSA.
Description:
The primary aim of this project is to determine the clinical effectiveness in infants with
cleft palate (CP) of side-lying as compared to back-lying sleep positioning in reducing
oxygen desaturation resulting from obstructive sleep apnoea (OSA). This will be achieved:
- comparing oxygen saturation during sleep in the side- and back-lying positions at 1
month of age.
- comparing sleep quality between the side-lying and back-lying groups using a parental
questionnaire.
- co-developing national recommendations with parents regarding sleep position for infants
with CP.
A randomised controlled trial (RCT) of side-lying compared with back-lying sleep positioning
in reducing oxygen desaturation resulting from OSA in infants with CP. The design and conduct
of the study will benefit from lessons learned from the feasibility and other previous
studies. All parents in the feasibility study indicated strong interest to participate in
further studies evaluating the effects of sleep position. Infants meeting the eligibility
criteria will be randomised to side-lying or back-lying in a ratio 1:1 using a minimisation
routine incorporating a random element to reduce predictability. Minimisation factors will be
clinical site and syndrome suspected or indicated (yes / no). Allocations will be delivered
via a password-protected web-based system. The allocated position will only be used on the
day(s) when the infant is monitored for the study purposes. Thereafter, parents will be free
to revert back to the standard sleep position as advised by their cleft centre, should it be
different than that used for the monitoring period. All centres represented at the
preparatory meeting with the United Kingdom (UK) Lead Clinical Nurse Specialist group,
confirmed that the side-lying position was recommended in some infants at their centre,
irrespective of whether it was the standard advice used. As such, all centres had experience
of the side-lying position. It was decided not to change the specific advice that centres
give to parents regarding how to position the infant in a side-lying position, but any
standard written or verbal information would be collected by the study documents.
An internal pilot will investigate participants' opinions about their participation in the
study. Using bespoke questionnaires participants' experience will be assessed and it will be
decided how it could be improved. After 6 months questionnaire results will be analysed and
if necessary study amendments will be put in place to reflect participants' opinions.
Data from the feasibility study and published studies have reported estimates of the standard
deviation (SD) of the primary outcome ODI-4 in the side-lying infants at four weeks to range
from 8 to 11 units, with a higher SD observed in the back-lying group. The observed
difference in mean ODI-4 between the side-lying and back-lying infant cohorts was 15 units (a
standardised effect size of 0.91). Investigators considered a smaller but more realistic
difference in means of five units to be a clinically important difference (SD 10), a
standardised effect size of 0.5. The sample size calculation comparing two means with unequal
variances for the primary outcome was, therefore, based on a standardised effect size of 0.5.
To account for potential unequal variances in each group a variance ratio of 2 was used in
the calculations. To detect a difference of 0.5 standard deviation score (SDS) with 80% power
and alpha equal to 0.05 would require 96 infants to be monitored in each arm of the trial (a
total of 192 participants). Informed by the multicentre feasibility and oximetry studies the
sample size will be inflated to 244 participants in the RCT, to allow for potential attrition
of 21%.
This will follow a pre-specified and approved statistical analysis plan. The primary analysis
of the RCT data will use intention-to-treat. Baseline data will be analysed to assess the
comparability of the demographic and clinical characteristics of the participants. Data from
the trial arms will be compared using generalised linear models and adjusted for minimisation
covariates where appropriate. Estimates of treatment effect size will be reported as
differences in means for continuous outcomes, and risk ratios for dichotomous outcomes and
reported along with 95% confidence intervals. Subgroup analyses will explore the effects of
sleep position on infants with and without suspected associated syndromes through subgroup
treatment interactions, at a stricter alpha level 0.01.
