Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000794606
Ethics application status
Approved
Date submitted
14/07/2014
Date registered
28/07/2014
Date last updated
27/11/2019
Date data sharing statement initially provided
27/11/2019
Date results information initially provided
27/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
To investigate the types of abnormal breathing patterns in patients with Motor neurone disease (MND) and to assess the usefulness of an 'intelligent' respiratory support device in patients who develop respiratory failure
Scientific title
A prospective study to systematically assess the nature and time course of sleep disordered breathing and respiratory failure in patients with motor neurone disease and to study the effects of auto-bilevel positive airway pressure [BiPAP] ( with variable expiratory positive airway pressure[EPAP]) vs. standard bilevel positive airway pressure [BiPAP]- spontaneous/timed (S/T) mode , in patients requiring non invasive ventilation(NIV) as per current guidelines
Secondary ID [1] 284978 0
Nil known
Universal Trial Number (UTN)
U1111-1159-2858
Trial acronym
BreatheMND-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Motor Neurone Disease 292480 0
Ventilatory failure 292481 0
Condition category
Condition code
Respiratory 292791 292791 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is an prospective observational study with a phase II randomised controlled arm. We have previously demonstrated( retrospective observational study) that patients with motor neurone disease( MND) develop a spectrum of various types of sleep disordered breathing.
Aims:
1. A prospective study of 40 patients to delineate the nature and time course of sleep disordered breathing in MND patients referred to the Repatriation General Hospital MND clinic for assessment.
2. Detailed sleep studies of Auto BiPAP ( using BiPAP A 40 AVAPS AE mode AE mode with auto pressure support, auto EPAP and auto back-up rate) vs. currently recommended BiPAP-S/T using a cross-over randomized 2 overnight study design ( consecutive nights), to assess the acute effects of each treatment in patients with respiratory failure, followed by randomization to one of the two treatments and clinical follow-up for 6 months ( minimum).
This part of the study will include all the patients who meet the criteria for NIV as per the current guidelines. There is no washout period between the two nights, for the cross-over trial.
Intervention code [1] 289805 0
Treatment: Devices
Comparator / control treatment
Active control using the standard BiPAP S/T mode
Control group
Active

Outcomes
Primary outcome [1] 292639 0
Adequacy of nocturnal ventilation on NIV as measured by lowest oxygen saturation, time spent with oxygen saturation <90%, oxygen desaturation index (ODI), minimum oxygen saturation and morning arterial blood gases
Timepoint [1] 292639 0
At the time of randomisation ,three and 6 months after randomisation
Primary outcome [2] 292640 0
Sleep quality as measured by apnea hypopnea index( AHI), Arousal index, sleep efficiency and amount of REM sleep.
Timepoint [2] 292640 0
At the time of randomisation and also 3 and 6 months
Secondary outcome [1] 309398 0
Quality of life as measured by ALS functional rating scale, Calgari sleep apnea quality of life index (SAQLI) and Short form 36(SF 36
Timepoint [1] 309398 0
At the time of randomisation, 3 months and six months

Eligibility
Key inclusion criteria
a) Age 18 or older
b) Patients diagnosed to have MND as per El Escorial criteria
c) Ability to give informed consent
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
a) Patients already on NIV
b) Cognitive impairment limiting the ability to participate in the trial
c) Decompensated heart failure as defined by sudden or gradual onset of symptoms or signs of heart failure requiring unplanned clinic visits, hospitalization of emergency department visits within past 3 months or Left ventricular ejection fraction less than 40%
d) Recent stroke (within 6 months)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 2 / Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/08/2014
Actual
11/02/2015
Date of last participant enrolment
Anticipated
Actual
25/05/2017
Date of last data collection
Anticipated
30/08/2018
Actual
6/05/2018
Sample size
Target
40
Accrual to date
Final
37
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 15345 0
Repatriation General Hospital - Daw Park
Recruitment postcode(s) [1] 28656 0
5041 - Daw Park

Funding & Sponsors
Funding source category [1] 289596 0
Charities/Societies/Foundations
Name [1] 289596 0
The Repat Foundation
Country [1] 289596 0
Australia
Primary sponsor type
Individual
Name
Vinod Aiyappan
Address
Adelaide Institute for Sleep Health
Repatriation General Hospital
Daws Road
Daw Park
SA 5041
Country
Australia
Secondary sponsor category [1] 288280 0
None
Name [1] 288280 0
Address [1] 288280 0
Country [1] 288280 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291331 0
Southern Adelaide Clinical Human Research Ethics Committee (SAC HREC)
Ethics committee address [1] 291331 0
Research Ethics Office
The Flats, G5 - Rooms 3 and 4
Flinders Drive
Flinders Medical Centre
Bedford Park SA 5042
Ethics committee country [1] 291331 0
Australia
Date submitted for ethics approval [1] 291331 0
31/07/2014
Approval date [1] 291331 0
11/12/2014
Ethics approval number [1] 291331 0
418.14 - HREC/14/SAC/437

Summary
Brief summary
Respiratory failure is the major cause of mortality and morbidity in patients with MND. Non-invasive ventilation provides respiratory support via a mask and machine and has become part of standard care for MND patients who develop sleep symptoms or respiratory failure. The current recommendations for NIV are mainly based on one study which reported that NIV prolonged survival and increased quality of life in a sub-group of patients with MND. However this study had only 22 patients in the NIV treatment group and NIV settings were changed based on patient tolerance and daytime blood gas changes, rather than in response to the type of abnormal breathing. In clinical practice, NIV is initially delivered during sleep, but is sometimes extended to the daytime as the disease progresses. The usual mode of NIV requires that the patient generates sufficient inspiratory effort to trigger pressure delivery by the machine. Inspiratory (and expiratory) pressure levels are usually chosen empirically without a sleep study. In a recent preliminary study including more systematic sleep studies, we found that NIV as currently provided to MND patients is suboptimal and in some instances may be dangerous. MND patients showed a variety of breathing abnormalities including obstructive apnea (a clinically silent variant not associated with snoring), central sleep apnea and varying levels of hypoventilation. Consequently, the traditional “one size fits all” approach to NIV treatment using empirically determined pressure settings is clearly sub-optimal. This project aims, for the first time, to characterize the patterns of abnormal breathing in MND patients and to investigate changes in breathing abnormalities as the disease progresses. We will also test the usefulness of a new “smart” ventilator in MND patients. This will help clarify the nature of gradually progressive deteriorations in breathing and how best to tailor treatments to improve breathing, sleep, quality of life and survival in patients with MND.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 49914 0
Dr vinod aiyappan
Address 49914 0
Adelaide Institute for Sleep Health
Repatriation General Hospital
Daws Road
Daw Park
SA 5041
Country 49914 0
Australia
Phone 49914 0
+61 8 82751187
Fax 49914 0
+61 8 8277 6890
Email 49914 0
[email protected]
Contact person for public queries
Name 49915 0
Dr vinod aiyappan
Address 49915 0
Adelaide Institute for Sleep Health
Repatriation General Hospital
Daws Road
Daw Park
SA 5041
Country 49915 0
Australia
Phone 49915 0
+61 8 82751187
Fax 49915 0
+61 8 8277 6890
Email 49915 0
[email protected]
Contact person for scientific queries
Name 49916 0
Dr vinod aiyappan
Address 49916 0
Adelaide Institute for Sleep Health
Repatriation General Hospital
Daws Road
Daw Park
SA 5041
Country 49916 0
Australia
Phone 49916 0
+61 8 82751187
Fax 49916 0
+61 8 8277 6890
Email 49916 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.