E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008908 |
E.1.2 | Term | Chronic heart failure |
E.1.2 | System Organ Class | 100000004849 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10022970 |
E.1.2 | Term | Iron deficiency |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 principal research question addressed by this trial is to assess the effect of intravenous repletion of iron on the ability of the heart to produce energy in iron deficient heart failure patients. |
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E.2.2 | Secondary objectives of the trial |
The secondary research questions are the following: 1. The differential impact of iron repletion on anaemic and non-anaemic iron deficient heart failure patients in exercise capacity 2. The differential impact of iron repletion on anaemic and non-anaemic iron deficient heart failure patients in cardiac structure and function 3. The differential impact of iron repletion on anaemic and non-anaemic iron deficient heart failure patients in myocardial iron content 4. The differential impact of iron repletion on anaemic and non-anaemic iron deficient heart failure patients in blood markers of disease and iron status (e.g., iron status, electrolytes, full blood count, metabolic bloods) 5. The differential impact of iron repletion on anaemic and non-anaemic iron deficient heart failure patients in symptoms 6. The differential impact of iron repletion on anaemic and non-anaemic iron deficient heart failure patients in Quality of Life (QoL). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Aged 18 to 89 years • Ferritin <100 mcg/l or Ferritin 100 – 300 mcg/l with TSAT <20% • Anaemic group (50% of study population): Hb <120 g/L in Females and Hb <130 g/L in Males • Non-anaemic group (50% of study population): Hb ≥120 g/L in Females and ≥130 g/L in Males • Stable New York Heart Association (NYHA) class II-IV symptoms for the preceding 4 weeks • LVEF ≤ 45% assessed by Echocardiography or Cardiac MRI within the preceding 6 months • On optimally tolerated heart failure drugs for ≥ 4 weeks with no changes (dose or medication type) for the preceding 2 weeks • Resting blood pressure ≤ 160/100mmHg • Negative pregnancy test in premenopausal females.
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E.4 | Principal exclusion criteria |
• Inability to provide written informed consent • Inability to sufficiently understand information pertaining to the conduct of the trial • Contraindications to 31P-MRS (e.g. pacemaker, metal prosthesis, etc) • Ischaemic cardiomyopathy • Folate and vitamin B12 levels below laboratory normal limit. • Use of erythropoietic agent, blood transfusion or immunosuppressive therapy in the preceding 30 days, or ongoing anticipated need for these agents during the study. • Acute or chronic bleeding, infective or inflammatory disorders (Rheumatoid Arthritis, Lupus, HIV/AIDS, malignancy, etc.) • History of iron overload or haemochromatosis in patient or first degree relatives. • Prior intolerance to intravenous iron formulations or any of their excipients • Chronic liver disease and/or aspartate transaminase (AST) >3 times the upper limit of the normal range • Renal dialysis (Haemodialysis or peritoneal dialysis) • Severe asthma or any severe lung disease with FEV1<50% of predicted or necessitating domicillary oxygen or non-invasive ventilation. • Severe atopic disorder including eczema or any prior anaphylactoid / anaphylactic reaction. • Haemolytic or myelodysplastic anaemia • Severe uncorrected non-functional valvular disease or left ventricular outflow obstruction, obstructive cardiomyopathy, uncontrolled fast atrial fibrillation or flutter (>110 bpm), uncontrolled symptomatic brady- or tachyarrhythmias. • Musculoskeletal limitation that, in the investigators judgement, would impair exercise testing. • Pregnant or breast feeding • Contemporaneous enrolment in another clinical trial
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E.5 End points |
E.5.1 | Primary end point(s) |
Cardiac Phosphocreatine to ATP ratio (PCr:ATP) measured by 31Phosphorus Cardiac Magnetic Resonance Spectroscopy. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
PCr:ATP ratio will be assessed at baseline and at 4 weeks after treatment. |
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E.5.2 | Secondary end point(s) |
1.Change from baseline to week 4 in exercise capacity as assessed by the 6 minute walk distance (6MWD) 2.Change from baseline to week 4 in cardiac structure and function as assessed using magnetic resonance imaging (MRI) and echocardiography 3.Change from baseline to week 4 in myocardial iron content as assessed by T2* value on Cardiac MRI. 4.Change from baseline to week 4 in blood tests (e.g., iron status, electrolytes, full blood count, metabolic bloods) 5.Change from baseline to week 4 in symptoms (as assessed by New York Heart Association [NYHA] class and Visual Analogue Fatigue Scale [VAFS]). 6.Change from baseline to week 4 in Quality of Life (QoL) as assessed by the Kansas City Cardiomyopathy Questionnaire [KCCQ]. 7.Number and incidence of adverse events
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At baseline and at 4 weeks after treatment allocation |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
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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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 | 8 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |