Condition category
Circulatory System
Date applied
11/11/2011
Date assigned
13/12/2011
Last edited
18/03/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Diagnosing the causes of blackouts can take many months, using tests that can be lengthy and uncomfortable. A new test, lasting a few minutes, using a drug called adenosine has been used in a number of hospitals across the world to help uncover the cause of blackouts. In this study we hope to find out whether or not the adenosine test can identify those with blackouts who could be treated with the implantation of a pacemaker.

Who can participate?
It is planned that a total of 180 patients will participate in the study, 90 who will receive a pacemaker and a further 90 who will receive an implantable loop recorder (a device implanted under the skin that records heart rate and ECG for up to 3 years).

What does the study involve?
We are asking patients who present to the Accident and Emergency Department or Medical Assessment Suite at the Royal Victoria Infirmary, Newcastle upon Tyne (UK) with a blackout and in whom the reason for the blackout is not clear following a description of the event, a physical examination, blood pressure measurements lying down and standing up and an electrocardiogram (ECG; recording of the heart rate and rhythm) to participate. If they agree to participate after a minimum of 24 hours to think things over arrangements will be made to bring them to the Falls and Syncope Service at the Royal Victoria Infirmary, Newcastle upon Tyne at no cost to themselves. They will be given a dose of 20 mg adenosine directly into a vein in the arm whilst attached to a cardiac monitor. Should there be temporary block of the electrical connection between the top and bottom chambers of the heart for more than 10 seconds or temporary halting of the heart’'s own pacemaker activity for greater than 6 seconds then the adenosine test is deemed to be positive. Should neither of these things happen, the test is deemed negative. Those who have a positive test will be asked to consent to the implantation of a permanent pacemaker which will be done in Cardiac Catheter Laboratory at the Freeman Hospital, Newcastle upon Tyne. The pacemaker is a device which sits under the skin under the left collar-bone in the hollow of the shoulder and connects to the heart through two leads which travel in the vein that leads back to the heart from the arm. It is designed to detect slow heart rates/rhythms and treat them by stimulating the heart to beat. After implantation, the pacemaker will either be turned “on” (capable of treating slow heart rates) or turned “off” (capable only of monitoring slow heart rates). Neither the patient or the researcher will know whether or not your pacemaker is turned “on” or “off”. After six months, those who have had the pacemaker turned “off” will have it turned “on” and vice versa. Again, neither you nor the researcher will know in which mode the pacemaker is working. This is important to ensure that nobody can accidentally influence whether pacing affects you having further blackouts. Those who have a negative adenosine test will be asked to consent to the implantation of a loop recorder. This is a small device that sits under the skin below the left collar-bone like a pacemaker but does not have the leads that travel to the heart. It continuously monitors the heart rate/rhythm but cannot treat any slow heart rates. Both those who receive a pacemaker and those who receive a loop recorder will be asked to report any blackouts that happen over the course of the year by completing a diary that is sent by post every week (a pre-paid envelope will accompany the diary so that it cab be returned by post without any cost). Should a blackout happen we will arrange for you to come to the Freeman Hospital so that we can check the heart rate/rhythm recorded by the pacemaker or loop recorder.

What are the possible benefits and risks of participating?
Firstly, the administration of adenosine can have side effects which include flushing, light-headedness, a sensation of difficulty in breathing, nausea and chest pressure but these last for a very short period of time (a few seconds up to a minute at most). Less commonly people can have sweating, nervousness, blurred vision, a metallic taste or a burning sensation and a fast heart rate for a few minutes. On very rare occasions people may blackout for a very short time during the test. These side effects are only found at the time of injection. The implantation of a permanent pacemaker is a well-tolerated and generally safe procedure but there are risks attached. The most serious potential risk is a puncture of the lung (pneumothorax) that occurs in 2% of cases but is readily treatable. The most common risk is displacement of one of the leads within the heart requiring another procedure to reposition it that occurs in 5% of cases. Other important risks are those of infection and haematoma (collection of blood) formation around the pacemaker requiring a further procedure that occurs in 1% of cases. A general anaesthetic is not required for the procedure. The implantation of a loop recorder is more straightforward than a pacemaker and is very safe with less than 1% chance of bleeding/infection. There is no risk of a pneumothorax or lead displacement.

Where is the study run from?
Royal Victoria Infirmary and Freeman Hospital in Newcastle upon Tyne (UK)

When is the study starting and how long is it expected to run for?
December 2011 to December 2015

Who is funding the study?
The research is funded by the British Heart Foundation and by Medtronic Inc, a pacemaker company who supplies some of the devices.

Who is the main contact?
1. Dr Iain Matthews (Research Doctor), iain.matthews@nuth.nhs.uk
2. Dr Steve W Parry (Chief Investigator), steve.parry@nuth.nhs.uk

Trial website

Contact information

Type

Scientific

Primary contact

Dr Steve Parry

ORCID ID

Contact details

Falls and Syncope Service and Institute for Ageing and Health
Royal Victoria Infirmary
Newcastle upon Tyne
NE1 4 LP
United Kingdom
+44 (0)191 282 5893
steve.parry@nuth.nhs.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

NCT01481168

Protocol/serial number

5883

Study information

Scientific title

Adenosine testing to DEtermine the need for Pacing Therapy with the additional use of an Implantable Loop Recorder (ADEPT-ILR study) - the efficacy of permanent pacing in patients presenting to emergency medical services with syncope and a positive intravenous adenosine: a randomised, double-blind, placebo-controlled, cross-over trial

Acronym

ADEPT-ILR

Study hypothesis

A permanent pacemaker implant in those with a positive intravenous adenosine test will prevent further syncopal episodes (which are secondary to bradycardia).

The intravenous adenosine test has been shown in small studies to identify bradycardia pacing indications. Permanent pacemaker implantation is the definitive treatment for bradycardia.

Ethics approval

NRES Committee North East - Newcastle and North Tyneside 2, 06/02/2012, ref: 11/NE/0373

Study design

Randomised double-blind placebo-controlled cross-over trial

Primary study design

Interventional

Secondary study design

Randomised cross over 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

Syncope

Intervention

1. Administration of 20mg intravenous adenosine
2. Dual chamber permanent pacemaker implantation and subsequent randomisation to ODO or DDD+/-R pacing
3. Implantable loop recorder insertion

Intervention type

Device

Phase

Drug names

Primary outcome measures

Syncope burden as measured by number of syncopal episodes and recorded by weekly postal patient diaries with telephone reminders to ensure adequate return

Secondary outcome measures

1. Time to first syncope
2. Number of patients with recurrent syncope
3. Quality of life as measured via the condition-specific instrument the Impact of Syncope on Quality of Life questionnaire with general health-related quality of life measured via the WHOQoL-Brief and WHOQoL-Old instruments
4. Health economic analysis: Costs and benefits of the intervention to health and social services.
4.1. Use of EQ-5D questionnaire to establish the cost per Quality Adujusted Life Year (QALY)
4.2. The analysis will include the patients described above as well as a historical comparator group of consecutive patients derived from the database held by the Falls and Syncsope Service who have not undergone adenosine testing. This group is particularly important to establish the utility of adenosine testing in the diagnosis of unexplained syncope.
5. ECG diagnosis on ILR following syncopal episode in adenosine negative group

Overall trial start date

01/12/2011

Overall trial end date

01/12/2015

Reason abandoned

Eligibility

Participant inclusion criteria

1. Patient has provided written informed consent for participation in the study prior to any study specific procedures
2. Male or female
3. Age 40 years or above
4. No cause of syncope clearly identified on clinical examination, lying and standing blood pressure measurements and standard 12 lead electrocardiogram (ECG)

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

180

Participant exclusion criteria

1. Asthma or chronic obstructive pulmonary disease
2. Severe coronary disease:
2.1. Myocardial infarction within 3 months
2.2. Known coronary stenosis >70%
2.3. NYHA heart failure or angina symptoms Class III or IV)
3. Known severe cerebrovascular disease or known significant internal carotid artery stenosis (>70%)
4. Prolonged corrected QT interval
5. Unablated accessory pathway
6. Pregnancy or lactation
7. Use of dipyridamole or any rate-limiting medication that cannot be safely discontinued
8. Hypertrophic cardiomyopathy
9. Cardiac transplantation
10. Concurrent participation in another investigational study or trial
11. Inability to give informed consent; carer/proxy assent will be allowed in this study
12. Cause of syncope established from initial clinical history and examination, lying and standing blood pressure and ECG

Recruitment start date

01/12/2011

Recruitment end date

01/12/2015

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal Victoria Infirmary
Newcastle upon Tyne
NE1 4 LP
United Kingdom

Sponsor information

Organisation

Newcastle upon Tyne NHS Foundation Trust (UK)

Sponsor details

c/o Ms Amanda Tortice
Joint Research Office
Royal Victoria Infirmary
Newcastle upon Tyne
NE1 4LP
United Kingdom
+44 (0)191 282 5959
amanda.tortice@ncl.ac.uk

Sponsor type

Hospital/treatment centre

Website

http://www.newcastle-hospitals.org.uk/

Funders

Funder type

Charity

Funder name

British Heart Foundation Clinical Research Training Fellowship (UK) ref: FS/11/13/28690

Alternative name(s)

BHF

Funding Body Type

private sector organisation

Funding Body Subtype

foundation

Location

United Kingdom

Funder name

Medtronic Inc (USA) are providing 25 permanent pacemakers and 25 implantable loop recorders free of charge for the duration of the treatment phase of the study

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

To be confirmed at a later date

Intention to publish date

01/08/2017

Participant level data

Stored in repository

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

On 18/03/2016 the overall trial end date was changed from 31/10/2013 to 01/12/2015. 09/03/2016: No publications found, verifying study status with principal investigator.