E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Adenosine administered intravenously slows heart rate, and over the last decade, the drug has been used in many centres in the diagnosis of unexplained syncope (blackouts). However, there is no clear consensus on which underlying disorder is being uncovered. Various researchers propose heart conducting tissue disease (sick sinus syndrome [SSS] and [AVB]) and neurally mediated syncope (carotid sinus syndrome [CSS] and vasovagal syncope [VVS - an exaggerated version of the common faint]) as the conditions diagnosed by adenosine. We propose the first ever study to tackle these issues comprehensively and systematically. The principal research objective will be to compare the heart rate response to adenosine with the underlying diagnosis in patients with SSS, AVB, CSS and VVS and healthy controls. |
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E.2.2 | Secondary objectives of the trial |
We also hope to define an abnormal response to adenosine (duration of heart block and/or asystole discriminating an abnormal response from a normal one) and further evaluate the tolerability of the procedure. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Consecutive patients over 18 years with dual chamber permanent pacemakers implanted for SSS, AVB and CSS at Freeman Hospital during the first 8 months of the study, and if additional numbers are needed, over the last 5 years identified retrospectively, will be asked to participate, as will consecutive patients with tilt-diagnosed VVS. In addition: ·SSS and CSS patients must be in sinus rhythm (SR), or if suffering paroxysmal atrial fibrillation, in sinus rhythm (SR) for >50% of the time (from pacemaker diagnostics). ·AVB patients must have underlying SR with normal AV conduction for >90% of the time. |
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E.4 | Principal exclusion criteria |
Inability to give informed consent, severe coronary disease (known coronary stenosis >70%, NYHA heart failure or angina symptoms Class III or IV), known severe cerebrovascular disease, myocardial infarction within 3 months, long corrected QT interval, uncorrected accessory pathway, history of asthma, COPD, pregnancy or lactation, dipyridamole or digoxin use, hypertrophic cardiomyopathy, cardiac transplantation, or known significant internal carotid artery stenosis (>50%). In addition: ·Patients with SSS: Persistent atrial fibrillation (AF); evidence of high degree AV block; complete AV block present for more than 10% of the time. If there is uncertainty regarding this, the lower rate of the device will be reduced and AV delay extended to assess underlying rhythm and AV conduction, with reassessment 1 month later. ·Patients with AVB: Evidence of sinus node disease as assessed by the amount of atrial pacing at pacemaker check. If uncertainty, the lower rate will be reduced and pacemaker rechecked at one month. ·Patients with CSS: Persistent AF or high degree AV block. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome measures will be the sensitivity and specificity of the adenosine test in diagnosing SSS, AVB, CSS and VVS based on the current European Society of Cardiology guidelines, namely >6 seconds asystole or >10 seconds high degree AVB. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Yes |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Information not present in EudraCT |
E.6.5 | Efficacy | Information not present in EudraCT |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Patients with AV block, sinus node disease, carotid sinus syndrome, vasovagal syncope, controls. |
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E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the trial will occur when all participants have undergone the relevant investigations, including adenosine testing. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |