Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT02748681 |
| Other study ID # |
HOPESV3 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
April 2016 |
| Est. completion date |
August 2018 |
Study information
| Verified date |
August 2018 |
| Source |
Neurologisches Rehabiliationszentrum Rosenhügel |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Study Objectives:
Meta-analyses report a high prevalence of moderate to severe sleep apnea of more than 50% in
stroke patients, with adherence rates for CPAP therapy of only 30%.
The primary objective of this study is to determine whether CPAP adherence in stroke patients
with obstructive sleep apnea can be improved by a CPAP training strategy during
rehabilitation combined with a telemedicine monitoring system after discharge.
The secondary objective is to compare recording quality as well as subjective and objective
sleep data of non-attended level III polygraphy, polysomnography and telemetric CPAP data in
the management of sleep apnea in stroke.
Further the investigators aim to study changes in nocturnal systolic blood pressure due to
CPAP therapy with the pulse transit time method.
Finally, the investigators intend to study the relationship between CPAP compliance, sleep
and medical and neurorehabilition outcome parameters.
Design:
Single-blind, mono-center, randomized controlled trial on standard CPAP treatment as compared
with CPAP treatment with a telemedicine monitoring system in stroke patients with moderate to
severe OSA.
Setting: Neurorehabilitation center in Vienna, Austria
Patients: Adult subacute (1 to 12 months post stroke) stroke patients 18-70 yrs of age) with
moderate to severe OSA (apnea hypopnea index (AHI) ≥ 15/hr) determined by non-attended
polysomnography (AHI) ≥ 15/hr of sleep) or level III polygraphy (AHI) ≥ 30/hr of
out-of-center sleep testing (OCST), who undergo successful CPAP training and titration (goal
AHI< 10) at the neurorehabilitation unit.
Interventions: Patients will be randomized to either standard care with an autotitrating CPAP
device or an autotitrating CPAP device that transmits physiologic information (i.e.,
adherence, air leak, residual AHI) daily to a website that will be reviewed by their homecare
provider. If any problems are identified, the patient will be contacted by his homecare
provider by telephone. Neurologists performing sleep and neurological scoring will be blinded
to the randomization.
Measurements: Recording of the different measuring systems, subjective and objective sleep
quality, CPAP adherence after 3 months and 1 year in hours used per night, systolic BP
determined by means of a non-linear algorithm and an individual one-point calibration of the
pulse transit time obtained with a cuff-based BP measuring system (SOMNOmedics GmbH, Germany)
and neurorehabilitation outcome parameters as Barthel Index, Timed Up and Go Test.
Description:
The investigators intend to perform a single-blind, mono-center, randomized controlled trial
on standard CPAP treatment as compared with CPAP treatment with a telemedicine monitoring
system in stroke patients with moderate to severe OSA.
Patients accepting CPAP therapy after successful titration will be randomized to either a
standard care or a telemedicine group (1:1 ratio) and will subsequently be informed about the
study arm by their homecare provider. The study was approved by the Clinical Research Ethics
Board of the public health services of Vienna.
Written informed consent for all examinations will be obtained upon patients` admission. If
patients agree to undergo CPAP monitoring, further informed consent will be obtained. The
study will be performed in accordance with the relevant guidelines of the Declaration of
Helsinki, 1964, as amended in Tokyo, 1975, Venice, 1983, Hong Kong, 1989, and Somerset West,
1996.
Screening Sleep Studies
Over the four to eight weeks of neurorehabilitation, each stroke patient ( 19-70 yrs of age)
will be offered a nocturnal respirographic screening evaluation of SA (see study flow chart).
Within the study period the investigators expect to screen 170 patients per year.
Diagnosis of sleep apnea and referral to CPAP training:
SA and referral to CPAP training will be based on an AHI ≥ 15/h sleep, as recommended by an
international task force on the standardization of definitions for sleep-related breathing
disorders to indicate moderate SA .
If screening with type-3 polygraphy reveals an AHI ≥ 15 and ≤ 30/h of recording time or if
subjective sleep time in the concomitant sleep log is less than 4 hours, non-attended
polysomnography will be performed to confirm the diagnosis of SA. If type-3 polygraphy shows
an AHI of ≥ 30/h recording time, the patient will directly be referred to CPAP therapy.
Polysomnography and polygraphy will be performed by a trained staff member using the
Somnomedics Diagnostic Systems (SOMNOmedics GmbH, Germany). Patients will be studied in their
hospital beds. Polygraphic and polysomnographic all-night recordings according to AASM
standard criteria will be obtained between approximately 22.00 (lights-out) and 6.00 am
(buzzer or alarm clock). Thus, time in bed (TIB) is fixed with 7.5 hours.
Polygraphic recording includes nasal air flow, snore train, thoracic and abdominal effort,
oxyhemoglobin saturation, and determination of the body position. Recordings will be used in
further investigations if at least 4 h of data can be obtained. EEG sleep data will include 6
EEG channels (F3-A2, F4-A1, C3-A2, C4-A1, O1-A2, O2-A1) according to the 10/20 system, 2
electrooculogram (EOG) channels (left/right), submental electromyogram (EMG) and tibialis
anterior electromyogram from both legs (EMG) and will be scored manually.
Systolic BP will be determined by means of a non-linear algorithm and an individual one-point
calibration of the pulse transit time obtained with a cuff-based BP measuring device
(SOMNOmedics GmbH, Germany). The number of systolic rises (defined as >15mmHg) in relation to
respiratory events and the maximum systolic blood pressure will be determined.
Patients will be asked to complete the Self-Assessment Scale for Sleep and Awakening Quality
(SSA) according to Saletu et al. (1987).
Polygraphic data recordings will be manually scored for apneas and hypopneas according to the
criteria developed by the American Academy of Sleep Medicine (AASM). For scoring an event as
a hypopnea, a 30% reduction of nasal flow associated with an oxygen desaturation of at least
3% is required. The AHI is defined as the sum of all apneas and hypopneas occurring per hour
of recording time.
CPAP Protocol
All patients referred to CPAP therapy will receive a 60-min PAP training. A nasal or oronasal
mask will be fitted to the patient's face by the PAP coordinator of our center, who is a
trained respiratory therapist and ESRS-certified somnologist (MS) with many years of
experience in sleep apnea patients.
Patients will be provided with an AirSense™ 10 AutoSet CPAP (Resmed) including a humifdifier.
This auto-titrating device monitors patients' airflow and adjusts pressure automatically to
eliminate sleep apnea.
The AirSense 10 AutoSet is able to differentiate between obstructive and central apneas. It
is set to auto-titrate at pressures between 6 and 13 cm H2O, which reflects our current
clinical practice. Pressure limits can be increased up to 16 cm H2O, but will be decreased to
the smallest range leading to a normalized AHI in order to avoid overtitration.
Patients accepting CPAP therapy after the training session will be motivated to use it for at
least 4 > hours sleep/night over one week. Additional nocturnal pulse oximetry will be
obtained. Patients will be coached by trained nurses during the night. Relatives will also be
trained in using the humidifier and cleaning the mask and the humidifier chamber. Data card
AHI, oximetry and leakage information will be collected every day. Pressure limits can be
increased or decreased to improve patient comfort. If patients consider the interface
uncomfortable, it may be changed.
After one week, patients with a median CPAP use of >4/hours will undergo unattended CPAP
polysomnography.
The quality of CPAP titration is graded as follows: optimal (obstructive AHI ≤ 5/h, supine
REM sleep on the treatment pressure; desaturation index≤ 5/h of sleep), good (obstructive AHI
< 10/h, REM sleep on the treatment pressure, desaturation index≤ 10/h), adequate (AHI < 10/h,
supine NREM sleep on the treatment pressure, desaturation index≤ 10/h). A persisting central
AHI < 5 will be tolerated. If none of these criteria are met, patients will be referred to
conventional attended CPAP polysomnograpy and excluded from the study.
Patients who chose to participate in the telemetric study part will be asked to sign informed
consent and will be randomized to either a standard care or a telemedicine group (1:1 ratio)
using sequentially numbered envelopes prepared by the CPAP homecare provider.
After receiving their prescribed CPAP device by their homecare provider they will be informed
in which group they are.
Study staff performing sleep recordings and clinical ratings will be blinded to the study
arm. In case of treatment pressure changes doctors will be informed about the study arm.
Clinical Scales
In both study arms patients will be asked to complete the following scales:
ESS (Epworth Sleepiness Scale) SSA (Self-Assessment Scale for Sleep and Awakening Quality
according to Saletu et al. 1987) QoL (Quality of Life Index according to Mezzich et al.) BQ
(Berlin Questionnaire) PAP Satisfaction Questionnaire
NIH Stroke Scale (National Institute of Health, National Institute of Neurological Disorders
and Stroke) TUG (Timed Up and Go Test) NHPT (Nine Hole Peg Test) BI (Barthel Index) Moca Test
Outpatient Monitoring after Randomization
Standard Care
Patients will be contacted by their homecare provider 2 days after receiving their CPAP
device and will be asked about progress and adherence,as well as about any problems that
might have occurred. After 3 months of therapy, patients will return to the hospital to see
the PAP coordinator and their doctor. Data on a variety of physiological variables, including
PAP adherence, PAP pressure applied, mask leakage, and residual respiratory events, will be
downloaded from their CPAP devices. Any problems with treatment may be addressed.
Patients will be asked to complete a number of clinical scales and answer a variety of survey
questions concerning side effects and sleep quality.
A non-attended PSG will be performed at the patients' homes.
Telemedicine Like in standard care, patients will receive an AirSense™ 10 AutoSet CPAP. In
addition, the telemedicine module of the PAP device will be activated by the homecare
provider. The module will be programmed to send physiological information (PAP adherence, PAP
pressure applied, mask leakage and residual respiratory events) to a web-based database via a
GPRS module every day.
Patients will be contacted by the homecare provider after 2 days and will be asked about
progress and compliance as well as about any problems. The PAP coordinator at the homecare
provider will review the downloaded information every morning except on weekends and holidays
and will contact the patient if any of the following occur: mask leakage of the 95 percentile
> 24 L/min, < 4 h of use for two consecutive nights, AHI > 10 events/h, and 90th percentile
of pressure > 16 cm H2O. The homecare provider will call the patient or his/her relatives and
will ask about symptoms such as dry mouth, mask issues, discomfort with the device, or any
other problems. If the only issue is low adherence due to lack of motivation, the homecare
provider will encourage the patient to use PAP. Should there be any other problems, the
homecare provider will discuss the case with the PAP coordinator (the same person that sees
the patients in the standard arm) and arrange for the patient to talk to or see the PAP
coordinator, depending on the patient's responses and the physiological data obtained.
Specific interventions may be performed to improve compliance that are considered standard at
the hospital (e.g., different mask, chin strap, modifications of pressure settings,
modifications of humidifier settings, saline nasal sprays).
After 3 months of therapy, patients will return to the hospital to see their doctor and the
data obtained will be reviewed (including CPAP pressure, mask leakage, residual respiratory
events, and compliance). Any problems with treatment may be addressed.
Like in the standard arm, polysomography will be performed at the patients' homes and
clinical scales will be completed.
Time Spent with Patients
The time our research coordinator or PAP coordinator spends with patients will be recorded
and written in a daily log sheet. This includes time spent fitting masks, problem solving,
talking with patients on the phone, meeting with patients, and reviewing downloaded or
transmitted information.
Statistical Analyses
Statistical analyses will be performed in SPSS version 10 for Windows (SPSS Inc. Chicago, IL,
USA). All P-values are two-sided and values < 0.05 are considered statistically significant.
To examine and compare demographic and test characteristics at inclusion, chi-sqare test,
t-test and Mann-Whitney U-test for independent samples will be used according to
distribution, which will be examined with the Kolmogorov-Smirnov Test. The primary outcome is
PAP adherence after 3 months (min used per day). To calculate the number of participants
needed for an effect size larger than 0,80 as proposed by Cohen (Statistical power analysis
for behavioural science. 1988), the investigators based a power calculation on the results of
the study by Fox et al. in patients with sleep apnea, comparing telemedicine versus standard
CPAP treatment over 3 months. The result of this calculation was 11 patients in one group.
Considering patients who will discontinue CPAP treatment, the investigators aim to include 55
patients in the randomisation process. Based on previous data the investigators consider that
168 patients will have to be included in the screening process for sleep apnea.
Clinical variables will be correlated with compliance data. Therefore the spearman rank
correlation coefficient and the pearson correlation coefficient will be used. Blood pressure
data at baseline and after 3 months of CPAP treatment will be compared.
