Condition category
Nervous System Diseases
Date applied
16/09/2005
Date assigned
05/10/2005
Last edited
18/03/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Contact information

Type

Scientific

Primary contact

Prof John Stradling

ORCID ID

Contact details

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

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

MOSAIC 1

Study information

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

Acronym

Multi-centre Obstructive Sleep Apnoea Interventional Cardiovascular Trial (MOSAIC)

Study hypothesis

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

Oxfordshire REC A, 15/12/2005, ref: 05/Q1604/159

Study design

Multi-centre randomised controlled

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Sleep apnoea

Intervention

Nasal CPAP machines versus no intervention

Intervention type

Device

Phase

Drug names

Primary outcome measures

1. Reduction in the cardiovascular risk using the Framingham score
2. Reduction in Epworth Sleepiness Score

Secondary outcome measures

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

Overall trial start date

02/01/2006

Overall trial end date

02/01/2009

Reason abandoned

Eligibility

Participant 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

Participant type

Patient

Age group

Adult

Gender

Male

Target number of participants

400

Participant 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

Recruitment start date

02/01/2006

Recruitment end date

02/01/2009

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Churchill Hospital
Oxford
OX3 7LJ
United Kingdom

Sponsor information

Organisation

Oxford Radcliffe Hospitals NHS Trust (UK)

Sponsor details

Research and Development Department
Manor House
John Radcliffe Hospital
Headley Way
Headington
Oxford
OX3 9DZ
United Kingdom

Sponsor type

Government

Website

Funders

Funder type

Charity

Funder name

British Heart Foundation (UK) - PG/05/068

Alternative name(s)

BHF

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2012 results in: www.ncbi.nlm.nih.gov/pubmed/23111478
2013 substudy results in: http://www.ncbi.nlm.nih.gov/pubmed/23702567
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23635945
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/24508706
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25182045
2015 results in: http://www.ncbi.nlm.nih.gov/pubmed/25979104
2016 results in: http://www.ncbi.nlm.nih.gov/pubmed/26983946

Publication citations

  1. Results

    Craig SE, Kohler M, Nicoll D, Bratton DJ, Nunn A, Davies R, Stradling J, Continuous positive airway pressure improves sleepiness but not calculated vascular risk in patients with minimally symptomatic obstructive sleep apnoea: the MOSAIC randomised controlled trial., Thorax, 2012, 67, 12, 1090-1096, doi: 10.1136/thoraxjnl-2012-202178.

  2. Substudy results

    Kohler M, Craig S, Pepperell JC, Nicoll D, Bratton DJ, Nunn AJ, Leeson P, Stradling JR, CPAP improves endothelial function in patients with minimally symptomatic OSA: results from a subset study of the MOSAIC trial., Chest, 2013, 144, 3, 896-902, doi: 10.1378/chest.13-0179.

  3. Results

    Schulz UG, Mason RH, Craig SE, Howard S, Nicoll DJ, Kohler M, Rothwell PM, Stradling JR, Leukoaraiosis on MRI in patients with minimally symptomatic obstructive sleep apnoea., Cerebrovasc. Dis., 2013, 35, 4, 363-369, doi: 10.1159/000348845.

  4. Results

    Turnbull CD, Craig SE, Kohler M, Nicoll D, Stradling J, Cardiovascular event rates in the MOSAIC trial: 2-year follow-up data., Thorax, 2014, doi: 10.1136/thoraxjnl-2013-204826.

  5. Results

    Stradling JR, Craig SE, Kohler M, Nicoll D, Ayers L, Nunn AJ, Bratton DJ, Markers of inflammation: data from the MOSAIC randomised trial of CPAP for minimally symptomatic OSA., Thorax, 2014, doi: 10.1136/thoraxjnl-2014-205958.

  6. Results

    Craig S, Kylintireas I, Kohler M, Nicoll D, Bratton DJ, Nunn AJ, Leeson P, Neubauer S, Stradling JR, Effect of CPAP on Cardiac Function in Minimally Symptomatic Patients with OSA: Results from a Subset of the MOSAIC Randomized Trial, J Clin Sleep Med, 2015.

  7. Results

    Schlatzer C, Bratton DJ, Craig SE, Kohler M, Stradling JR, ECG risk markers for atrial fibrillation and sudden cardiac death in minimally symptomatic obstructive sleep apnoea: the MOSAIC randomised trial, BMJ Open, 2016, 6, 3, e010150, doi: 10.1136/bmjopen-2015-010150.

Additional files

Editorial Notes

18/03/2016: Publication reference added.