Condition category
Circulatory System
Date applied
16/04/2014
Date assigned
25/06/2014
Last edited
25/06/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Central sleep apnoea (CSA) is a sleep disorder where the patient stops breathing for typically 10-30 seconds at a time, leading to a decrease in the amount of oxygen in the blood (blood oxygen saturation level). It affects up to half of patients with severe heart failure and is associated with a poor prognosis. It occurs when the brains respiratory control centres becomes imbalanced during sleep and is caused largely by an exaggerated response to rising carbon dioxide levels in the blood, which normally drives how hard we breath. Sufferers have episodes of not breathing, or very shallow breathing, followed by a period of deep, or sometimes rapid, breathing. Cardiac Resynchronization therapy (CRT), in which a pacemaker is implanted to improve co-ordinated contraction of the heart, has been shown to reduce the severity of CSA in some patients. We aim to determine whether this improvement is due to normalization of the body's response to carbon dioxide in the blood. Our hypothesis is that CRT improves CSA by normalizing the brain's response to carbon dioxide.

Who can participate?
Patients undergoing implantation of a biventricular pacemaker, with heart failure and an ejection fraction (volume of blood pumped from the heart when it beats) of less than 40%.

What does the study involve?
The study involves each participant taking part in a home sleep study assessment using a Embletta, (which monitors breathing pattern, airflow, the rise and fall of the chest and stomach, snoring, body position and oxygen levels when the person is asleep) before having their pacemaker is implanted. If the patient is found to have at least moderate CSA (experimental group), or if they have no significant CSA (control group), they will then be invited to have a carbon dioxide sensitivity test (Read-Rebreathe method). This involves breathing in and out of a bag for around 5 minutes. The depth and frequency of breathing is measured against the rising level of carbon dioxide in the air. This test will be repeated 6 weeks and 6 months after the pacemaker is implanted.

What are the possible benefits and risks of participating?
This study allows physicians to assess the patient's nocturnal breathing patterns and may lead to treatment for previously undiagnosed problems. The study is very safe with no appreciable risk.

Where is the study run from?
Royal Brompton and Harefield NHS Trust

When is the study starting and how long is it expected to run for?
April 2014 to October 2015

Who is funding the study?
Boston Scientific (USA)

Who is the main contact?
Dr Simon Pearse, Prof Cowie Research Office, Chelsea Wing, Royal Brompton Hospital, London, SW3 6NP.

Trial website

Contact information

Type

Scientific

Primary contact

Dr Simon Pearse

ORCID ID

Contact details

Royal Brompton Hospital
Sydney Street
London
SW3 6NP
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

16260

Study information

Scientific title

Sleep-disordered breathing in patients with implanted cardiac devices: assessment of the change in sensitivity to carbon dioxide with cardiac resynchronisation therapy - an observational case-controlled study

Acronym

Study hypothesis

Heart failure, where the output of blood from the heart is inadequate for the body's requirements, is a common clinical problem with a poor prognosis despite advances in pharmacological, surgical and pacing therapy. Around half of patients with heart failure suffer from sleep-disordered breathing (SDB). This may be obstructive sleep opnoea (OSA - due to decreased muscle tone in the throat and associated with obesity, predisposing to hypertension, stroke and heart disease) or central sleep apnoea (CSA). CSA is a type of SDB in which breathing may be excessively deep for a time and then very shallow or even cease for short periods. This pattern of breathing is associated with more severe heart failure and a poor prognosis. A novel algorithm (ApneaScan, Boston Scientific plc) has been developed on certain pacemakers to detect SDB. We are validating this algorithm in a parallel study.

The depth and frequency of breathing is predominantly influenced by the level of carbon dioxide in the blood. Rising levels of carbon dioxide stimulate the brain to make us breath harder, thereby restoring carbon dioxide levels back to baseline. One of the major causes of CSA is an exaggerated response to carbon dioxide, which is found in patients with heart failure. This sets in place a cycle of over-breathing followed by cessation of breathing. We aim to evaluate whether Cardiac Resynchronisation Therapy (CRT) via a biventricular pacemaker, which increases the efficiency of the heart and can improve heart failure symptoms and prognosis, has an effect on the brain's response to carbon dioxide and whether this depends on the presence or absence of CSA.

More details can be found here: http://public.ukcrn.org.uk/Search/StudyDetail.aspx?StudyID=16260

Ethics approval

Bromley Research Ethics Committee, 26/02/2014, 14/LO/0078

Study design

Non-randomised; Observational; Design type: Case-controlled study

Primary study design

Observational

Secondary study design

Case-control study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Condition

Topic: Cardiovascular disease; Subtopic: Cardiovascular (all Subtopics); Disease: Cardiovascular

Intervention

In this trial we are testing how the depth and frequency of breathing changes with rising inspired carbon dioxide levels. We will test this relationship before and after implantation of a biventricular pacemaker for the treatment of heart failure. This involves breathing in and out of a 5-litre bag using a mouthpiece similar to that found on a snorkel. As the patient breathes, the amount of carbon dioxide in the gas mixture rises, which stimulates faster and deeper breathing. We measure the carbon dioxide concentration against the depth and frequency of breathing (measured by a tachometer). The whole test takes around 20 minutes and the measurement period (whilst breathing in to the bag) around 5 minutes. Patients will be tested before the pacemaker is implanted, 6 weeks later and 6 months later. In addition, the patient's notes will be reviewed after 2 years to document adverse heart failure events.

Intervention type

Device

Phase

Not Applicable

Drug names

Primary outcome measures

Hypercapnic Ventilatory Response; Timepoint(s): Change in Minute Ventilation per unit rise in end tidal CO2.

Secondary outcome measures

Apnoeic-Hypopnoeic Index; Timepoint(s): Measured at 6 weeks and 6 months post-implantation of pacemaker.

Overall trial start date

09/04/2014

Overall trial end date

01/10/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Heart failure (of any aetiology) and a reduced ejection fraction (<40%) due to undergo implantation of a Boston Scientific biventricular pacemaker or defibrillator with the ApneaScan function
2. They must meet UK guidelines for biventricular pacemaker implantation
3. They should be on optimal medical therapy for heart failure
4. They must be aged 18 or over and be able to give valid written consent for this study
5. They must be ambulatory
Target Gender: Male & Female; Upper Age Limit 100 years ; Lower Age Limit 18 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 40; UK Sample Size: 40

Participant exclusion criteria

1. Patients receiving pacemakers without the ApneaScan function
2. Patients unable or unwilling to attend follow-up testing
3. Patients receiving devices for indications other than heart failure with reduced ejection fraction
4. Patients with obstructive sleep apnea already on continuous positive airway pressure (CPAP) therapy
5. Patients unable to walk

Recruitment start date

09/04/2014

Recruitment end date

01/10/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Brompton Hospital
London
SW3 6NP
United Kingdom

Sponsor information

Organisation

Royal Brompton & Harefield NHS Trust (UK)

Sponsor details

c/o Patrik Pettersson
Clinical Trials and Evaluation Unit
Sydney Street
London
SW3 6NP
United Kingdom
P.Pettersson@rbht.nhs.uk

Sponsor type

Hospital/treatment centre

Website

http://www.rbht.nhs.uk/

Funders

Funder type

Industry

Funder name

Boston Scientific (USA)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

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

Publication citations

Additional files

Editorial Notes