Adenosine Testing to DEtermine the Need for Pacing Therapy

Study Overview
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Brief Summary
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The purpose of this study is to determine whether or not the intravenous adenosine test readily identifies patients with unexplained syncope who would benefit from permanent pacemaker implantation.

Detailed Description
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The investigation of syncope (transient loss of consciousness with loss of postural tone, collapse and spontaneous recovery) varies widely, is often lengthy and frequently expensive. The intravenous adenosine test has been used in the investigation of syncope and is cheap, safe and free of serious side effects. However, it is unclear what diagnosis the test unearths. There is some evidence that the test readily identifies bradycardia pacing indications. In this study we plan to perform the adenosine test and implant a pacemaker should the test be positive. In half of the patients we will turn the pacemaker on and in the other half the pacemaker off. The groups will swap over after six months. During this time we will assess the number of syncopal episodes. Also, in those who have a negative adenosine test we will implant a loop recorder to try to discover the cause of syncope.

Official Title
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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 With Syncope and a Positive Intravenous Adenosine Test: a Randomised, Double-blind, Placebo-controlled, Cross-over Trial.

Conditions
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Syncope

Intervention / Treatment
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* Device: Pacemaker implantation (Medtronic)
* Device: Pacemaker implantation (Medtronic)
* Device: Implantable Loop Recorder (Medtronic)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Episode of syncope Patient has provided written informed consent for participation in the study prior to any study specific procedures Male or female Age > 40 years No cause of syncope clearly identified on clinical examination, lying and standing blood pressure measurements and standard 12 lead ECG. Exclusion Criteria: Asthma or chronic obstructive pulmonary disease Severe coronary disease (myocardial infarction within 3 months, known coronary stenosis >70%, NYHA heart failure or angina symptoms Class III or IV) Known severe cerebrovascular disease or known significant internal carotid artery stenosis (>70%) Prolonged corrected QT interval Unablated accessory pathway Pregnancy or lactation Use of dipyridamole or any rate-limiting medication that cannot be safely discontinued Hypertrophic cardiomyopathy Cardiac transplantation Concurrent participation in another investigational study or trial Inability to give informed consent; carer/proxy assent will be allowed in this study Cause of syncope established from initial clinical history and examination, lying and standing blood pressure and ECG

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Pacemaker on<br>DDD+/-R pacing | Device: Pacemaker implantation (Medtronic)<br>* DDD+/-R pacing<br>* Other names: Medtronic DDD+/-R pacemakers;|
| Placebo Comparator: Pacemaker off<br>ODO pacing | Device: Pacemaker implantation (Medtronic)<br>* ODO pacing<br>* Other names: Medtronic DDR+/-R pacemakers.;|
| Experimental: Implantable Loop Recorder<br>Implantable loop recorder in adenosine test negative patients | Device: Implantable Loop Recorder (Medtronic)<br>* Loop recorder implantation<br>* Other names: Medtronic Reveal DX or XT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Syncope Burden | Syncope Burden as measured by number of syncopal episodes and recorded by weekly postal patient diaries with telephone reminders to ensure adequate return | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first syncope | Time to first syncope | 12 months | 
| Number of patients with recurrent syncope | Number of patients with >1 episodes of syncope | 12 months | 
| Quality of life | 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 | 12 months | 
| Health economic analysis | Costs and benefits of the intervention to health and social services. (i) Use of EQ-5D questionnaire to establish the cost per Quality Adjusted Life Year (QALY) (ii) 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 Syncope 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. | 12 months | 
| ECG diagnosis on ILR following syncopal episode in adenosine negative group | ECG diagnosis on ILR following syncopal episode in intravenous adenosine test negative group | 12 months |