Multi-centre randomised controlled trial to investigate the efficacy of nasal continuous positive airway pressure treatment to reduce cardiovascular risk and symptoms in mild to moderate sleep apnoea

ISRCTN	ISRCTN34164388
DOI	https://doi.org/10.1186/ISRCTN34164388
Protocol serial number	MOSAIC 1
Sponsor	Oxford Radcliffe Hospitals NHS Trust (UK)
Funder	British Heart Foundation (UK) - PG/05/068

Submission date: 16/09/2005
Registration date: 05/10/2005
Last edited: 18/03/2016

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

http://www.ctu.mrc.ac.uk/research_areas/study_details.aspx?s=19

Contact information

Prof John Stradling
Scientific

Oxford Sleep Unit
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LJ
United Kingdom

Study information

Primary study design	Interventional
Study design	Multi-centre randomised controlled
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Multi-centre randomised controlled trial to investigate the efficacy of nasal continuous positive airway pressure treatment to reduce cardiovascular risk and symptoms in mild to moderate sleep apnoea
Study acronym	Multi-centre Obstructive Sleep Apnoea Interventional Cardiovascular Trial (MOSAIC)
Study objectives	Patients with Obstructive Sleep Apnoea (OSA) are treated with nasal continuous positive airway pressure (CPAP) to control excessive daytime sleepiness, and to reduce vascular risk by improving blood pressure (BP), and possibly other vascular risk factors. Randomised trials for one month have shown falls in BP following treatment for disease at the more severe end of the spectrum, but not for less severe disease where treatment benefits are currently unproven. If the treatment of less severe disease produces similar benefits, this will be a substantial therapeutic advance in vascular risk reduction, since this disease affects up to 6% of men. If ineffective, the substantial treatment costs would be better directed elsewhere. The randomised trial proposed here will determine whether treating less severe sleep apnoea reduces calculated vascular risk, surrogate measures of cardiovascular disease, symptomatic benefits, and will determine the feasibility of a subsequent phase 3, long-term, trial to quantify any actual reduction in vascular event rate.
Ethics approval(s)	Oxfordshire REC A, 15/12/2005, ref: 05/Q1604/159
Health condition(s) or problem(s) studied	Sleep apnoea
Intervention	Nasal CPAP machines versus no intervention
Intervention type	Device
Phase
Drug / device / biological / vaccine name(s)
Primary outcome measure(s)	1. Reduction in the cardiovascular risk using the Framingham score 2. Reduction in Epworth Sleepiness Score
Key secondary outcome measure(s)	1. Fall in insulin resistance 2. Fall in HbA1c 3. Platelet activation 4. BP variability 5. Fasting triglycerides 6. Obesity and its distribution 7. Carotid wall volume 8. Brain magnetic resonance imaging (MRI) indices of hypertensive damage 9. Diastolic function 10. Pulse wave analysis 11. Reduction in adverse cardiovascular events 12. Improvement in self assessed health status and ability to resist sleep 13. Reduction health services utilisation
Completion date	02/01/2009

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Male
Target sample size at registration	400
Key inclusion criteria	1. Objectively confirmed obstructive sleep apnoea on respiratory polysomnography, with a >4% arterial oxygen desaturation index of >7.5/hour 2. Written informed consent
Key exclusion criteria	1. Sleep apnoea symptoms of sufficient severity that CPAP is mandated by current trial evidence, such that randomisation to a control would be unethical (this decision is in the hands of the randomising physician as the equipoise point varies between units, but guidance on this is presented later) 2. Ventilatory failure (awake resting arterial oxygen saturation <93% or arterial pCO2 >6kPa) 3. Clinic BP more than 180/110 4. Cheyne-Stokes breathing on respiratory polysomnography 5. Current Heavy Goods Vehicle or Public Service Vehicle driving licence holder 6. Any sleep related accident 7. Age <45 or >75 years at trial entry (age range selected as it is typical for patients with OSA and will have a significant cardiovascular event rate) 8. Previous exposure to CPAP or non-invasive ventilation 9. Mental or physical disability precluding informed consent or compliance with the protocol for the duration of the study 10. Non-feasible trial follow-up (for example, distance from follow-up centre, physical inability) 11. Any co-incidental illness making survival for two years unlikely
Date of first enrolment	02/01/2006
Date of final enrolment	02/01/2009

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Churchill Hospital

Oxford
OX3 7LJ
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/12/2012		Yes	No
Results article	results	01/09/2013		Yes	No
Results article	substudy results	01/09/2013		Yes	No
Results article	results	01/10/2014		Yes	No
Results article	results	01/02/2015		Yes	No
Results article	results	15/09/2015		Yes	No
Results article	results	16/03/2016		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes

Editorial Notes

18/03/2016: Publication reference added.