E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cardiac allograft vasculopathy and elevated resting heart rate in heart transplant recipients |
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E.1.1.1 | Medical condition in easily understood language |
Chronic rejection (cardiac allograft vasculopathy) and elevated resting heart rate in patients that have recieved a heart transplantation |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007648 |
E.1.2 | Term | Cardiovascular disease, unspecified |
E.1.2 | System Organ Class | 100000004849 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate whether treatment with ivabradine (5 mg bid for 12 weeks) compared to placebo can improve exercise capacity in long-term heart transplant recipients with cardiac allograft vasculopathy and elevated heart rate at rest. Primary endpoint: To compare the efficacy between treatment groups by assessing the difference in exercise capacity by • Change in VO2 max (ΔVO2max)
- Change in |
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E.2.2 | Secondary objectives of the trial |
To evaluate whether treatment with ivabradine (5 mg bid for 12 weeks) compared to placebo can improve exercise capacity in long-term heart transplant recipients with cardiac allograft vasculopathy and elevated heart rate at rest. Seondary endpoints: To compare the efficacy between treatment groups by assessing the difference in • Change in resting HR (ΔHRrest) • Change in HR reserve (ΔHRreserve) • Change in LV mass by MRI (ΔLVmass) • Change in LVEF by MRI (ΔLVEF) • Change in LV diastolic function (Δ TTE and MRI diastolic parameters) • Quality of life (QOL)
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
There is one substudy related to this main study. The substudy is incorporated in the trial protocol and have the same title, date and version. The objectives of the substudy is as followes:
As a substudy invasive and noninvasive cardiac examinations (IVUS/NIRS, OCT, Rb-82 PET) are performed at baseline to evaluate the presence and severity of CAV and to obtain valuable insight into coronary vessel wall structure and composition in order to improve the characterization and understanding of CAV. The objectives of the substudy are: • To characterize coronary vessels in CAV using new imaging modalities and relating them to functional parameters of cardiac function
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E.3 | Principal inclusion criteria |
• Patients > 1 year post heart transplantation • CAV verified by coronary angiography or IVUS • Resting HR > 80 bpm • Age > 18 years • Signed informed consent
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E.4 | Principal exclusion criteria |
• Rejection (>H1R) < 3 months • Severe renal failure (estimated GFR < 30 mL/min/1.73 m2) • Inability or contraindication to perform a VO2max test • Presence of any condition that might per se influence exercise performance • Known contraindication for treatment with ivabradine • Hypersensitivity to the active substance or to any of the excipients of either study drug
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E.5 End points |
E.5.1 | Primary end point(s) |
• Change in VO2max (ΔVO2max) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
12 weeks from initiation of study medication |
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E.5.2 | Secondary end point(s) |
• Change in resting HR (ΔHRrest) • Change in HR reserve (ΔHRreserve) • Change in LV mass by MRI (ΔLVmass) • Change in LVEF by MRI (ΔLVEF) • Change in LV diastolic function (Δ TTE and MRI diastolic parameters. TTE: mitral deceleration time, E/é, E/A ratio, isovolumetric relaxation time. MRI: transmitral flow rate, pulmonary venous flow, LVEDV, LVESV, LV peak filling rate, time to peak filling) • QOL
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
12 weeks from initiation of study medication |
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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 | No |
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 | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | No |
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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The end of the trial is defined as the last visit of the last trial subject (LVLS). |
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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 | |
E.8.9.1 | In the Member State concerned days | |