E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Ambulatory patients with stable symptomatic chronic CHF (congestive heart failure) and iron deficiency. |
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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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002062 |
E.1.2 | Term | Anaemia iron deficiency |
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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 objective of this trial is to assess, relative to placebo, the effects on the evolution of exercise capacity (i.e. 6-minute walk test) and symptomatic status (i.e. New York Heart Association classification) of the addition of intravenous iron treatment with FCM (ferric carboxymaltose) to the basic regimen of ambulatory patients with stable symptomatic chronic CHF (congestive heart failure) and iron deficiency. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives are to evaluate the effect of intravenous FCM compared to placebo on: 1. Evolution from baseline of cardiac function parameters as assessed by 2D Echo/Doppler cardiography 4, 12 and 24 weeks after start of study treatment. 2. Self-reported patient global assessment (PGA) of treatment at 4, 12 and 24 weeks after start of study treatment. 3. Health related quality of life (HRQoL) as assessed by the EQ-5D (European quality of life – 5 dimensions) and KCCQ (Kansas City Cardiomyopathy Questionnaire) self-administered questionnaires 4, 12 and 24 weeks after start of study treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
At least 18 years of age who have provided written informed consent; In NYHA (New York Heart Association) functional class II or III, Ambulatory and capable of performing a 6-minute walk test; Treated for CHF (congestive heart failure) during at least one hospital, emergency room or acute clinic admission within the last 24 months or brain natriuretic peptide (BNP) ≥ 100 pg/ml or N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) ≥ 400 pg/ml, not older than 8 weeks when study treatment is started; Currently treated for CHF for at least 4 weeks with the same combination of at least two of the following: (a) diuretic, (b) beta-blocker (including carvedilol), (c) ACE (angiotensin converting enzyme inhibitor) or ARB (angiotensin II receptor blocker); Treated during the last 2 weeks with the same dose of drugs given for CHF (dose changes of diuretics are allowed); Resting cuff blood pressures ≤ to 160 mm Hg systolic and ≤ 100 mm Hg diastolic (at the disappearance of sounds, Korotkoff phase V); LVEF (left-ventricular ejection fraction) ≤ 40% assessed locally by 2D Echocardiography; Screening Hb (haemoglobin) value ≥ 9.5 g/dL (5.9 mmol/L), and ≤ 13.5 g/dL (8.4 mmol/L). Screening ferritin below 100 μg/L (224.7 pmol/l), or below 300 μg/L (674.1 pmol/l) when TSAT (transferrin saturation) is below 20%; Use of adequate contraceptive methods for women of childbearing potential. |
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E.4 | Principal exclusion criteria |
Unstable angina pectoris; Walking distance limited by intermittent claudication; Significant valvular disease or left ventricular outflow obstruction; Poorly controlled rapid atrial fibrillation or flutter, symptomatic brady- or tachyarrhythmia; Chronic liver disease; Active infection, clinically significant bleeding, life expectancy reduced by malignancy or known HIV/AIDS (human immunodeficiency virus/acquired immune deficiency syndrome); Anaemia due to reasons other than iron deficiency (e.g. haemoglobinopathy); On immunosuppressive therapy or renal dialysis; Pregnant or lactating; Hospitalisation, emergency room or acute clinic admission for CHF within the last 2 weeks; AMI (acute myocardial infarction) or CVA (cerebrovascular accident) within the last 12 weeks; PCI (percutaneous coronary intervention), CABG (coronary artery bypass graft), major surgery, CRT, ICD or ICD-CRT implantation within the last 12 weeks (diagnostic angiography is allowed); History of acquired iron overload or hypersensitivity to FCM (ferric carboxymaltose) or to any of its excipients; Erythropoiesis Stimulating agents (ESAs), i.v. or blood transfusion administered within the last 12 weeks, or oral iron therapy within the last 30 days; Participation in another clinical trial within the last 30 days; Inadequate quality for central analysis of locally recorded 2D Echo/Doppler cardiograms; Screening ALT (alanine transaminase) or AST (aspartate aminotransferase) > three times the local upper limit of normal; CRP (C-reactive protein) >20 mg/L; Immunosuppressive therapy, renal dialysis, EPO, i.v. or oral iron therapy, or blood transfusion planned; Present abuse of alcohol or drugs; Anticipated participation in another trial during this trial; Inability to fully comprehend and/or comply with trial procedures in the investigator’s opinion. |
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E.5 End points |
E.5.1 | Primary end point(s) |
In accordance with this trial’s primary objective, the two co-primary outcomes are: 1. Evolution from baseline of the distance covered during 6MWTs (6-minute walk tests) performed 4, 12 and 24 weeks after the start of study treatment. 2. Evolution from baseline in NYHA (New York Heart Association) functional class assessments performed at 4, 12 and 24 weeks after the start of study treatment. |
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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 | Yes |
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 | Yes |
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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 17 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | |
E.8.9.1 | In the Member State concerned months | 16 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 16 |