E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008908 |
E.1.2 | Term | Chronic heart failure |
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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 |
The primary outcome measures will be the effect of digoxin therapy on i) the mean ventricular heart rate and ii) the heart rate variability measured using 24 Holter monitoring. Other measures of autonomic function will be measured such as heart rate turbulance and heat rate recovery after exercise. The study aims to investigate the role of low dose digoxin in the modern management of heart failure, particularly when added to beta blocker therapy, of which no clear evidence exists. |
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E.2.2 | Secondary objectives of the trial |
1. Measure changes in systolic time intervals using acoustic cardiography or changes in heart contractility indices measured using impedance cardiography. 2. Changes in echocardiography measures of LV contractility and filling patterns. 3. Changes in NTproBNP level. 4. Changes in exercise varaibles during cardiorespiratory exercise testing. 5. Changes in functional status usi standardised heart failure questionnaire. 6. Changes in endothelial blood flow measured using laser and light spectroscopy |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Left ventricular ejection fraction ≤ 45% measured by echocardiography. 2. NTproBNP >100 pmol/L 3. NYHA functional class II-IV. 4. Treated with beta blocking agents. 5. Clinically stable on maximally tolerated heart failure therapeutics for ≥ 3 months. 6. All patients must be in sinus rhythm.
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E.4 | Principal exclusion criteria |
1. Currently prescribed digoxin or discontinued previously due to intolerance. 2. Allergy to Ascorbic acid or lactose. 3. Estimated Glomerular Filtration Rate <30mls/min. 4. Resting heart rate < 60/min. 5. 2nd or 3rd degree heart block, sinus node disorder or known accessory pathway or any other listed contraindications to digoxin in the British National Formulary (BNF). 6. Plasma potassium level < 3.5mmol/dl or >5.5 mmol/dl. 7. Plasma magnesium level < 0.6 mmol/dl. 8. Pregnant or breastfeeding. 9. Allergy to adhesive pads. 10. Age <18 or > 90 years old. 11. History of hypertrophic/constrictive or restrictive cardiomyopathy. 12. Permanently ventricular paced. 13. Mechanical valve replacement. 14. MI or stroke in the preceding 3 months. 15. Haemodynamically significant valvular disease. 16. Enrolled in trials involving other medicinal products. 17. Any patient planning to undergo a surgical or interventional procedure which falls within the study period.
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E.5 End points |
E.5.1 | Primary end point(s) |
i) Mean ventricular rate & ii) Heart rate variability (SDNN) on 24 hr Holter monitoring |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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 | Yes |
E.8.1.2 | Open | No |
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 | Yes |
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 | Yes |
E.8.2.3 | Other | No |
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 | No |
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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Inability to recruit sufficient patients to trial or significant numbers of patients withdrawing from the study. |
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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 | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |