E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
iron deficiency in patients with chronic heart failure |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10022970 |
E.1.2 | Term | 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 |
To determine, relative to placebo, the effect of iron repletion therapy using intravenous ferric carboxymaltose (Ferinject®) on self-reported patient global assessment (PGA) and NYHA functional status 24 weeks after initiation of therapy in patients with chronic heart failure and iron deficiency. |
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E.2.2 | Secondary objectives of the trial |
Main secondary objective: To evaluate the effect of intravenous ferric carboxymaltose (Ferinject®) compared with placebo on Exercise tolerance (6-minute walk test distance). Other secondary objectives: To evaluate the effect of intravenous ferric carboxymaltose (Ferinject®) compared with placebo on health related quality of life and to evaluate resource use and costs associated with the treatment with intravenous ferric carboxymaltose (Ferinject®) compared with placebo.
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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 |
Title: Determination of peak VO2 using exercise cardiopulmonary treadmill testing in Study FER-CARS-02. Date: 21 December 2006 Version: 1.1 Rationale: In order to gain additional data on exercise tolerance for comparison with the information from the 6-min walking test an exercise cardiopulmonary treadmill test to determine peak oxygen consumption (pVO2 ) will be performed.
The sub-study is planned to be conducted in about 90 patients (60:30) in 15-20 pre-selected centres, i.e. centres with the necessary equipment.
Additional sub-study specific exclusion criteria are: •Musculoskeletal limitations that, in the judgment of the investigator, would impair cardiopulmonary exercise testing •Inability to fully comprehend and/or perform sub-study procedures (according to investigator’s opinion)
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E.3 | Principal inclusion criteria |
1. At least 18 years of age and signed written informed consent. 2. In NYHA II-III functional class due to stable symptomatic CHF, and all of the following: a. Two weeks without cardiac hospitalisation. b. Patients in NYHA II must have had an acute care admission or emergency room visit for worsening of heart failure within 24 months prior to randomisation. c. On optimal conventional therapy (in general, optimal pharmacological treatment which includes a diuretic, a beta-blocker, and/or an angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) as determined by the investigator, unless contraindicated or not tolerated). d. No dose changes of heart failure drugs during the last 2 weeks (with the exception of diuretics). e. No introduction of a new heart failure drug class during the last 4 weeks. 3. Left ventricular ejection fraction (LVEF) 40% or lower for patients in NYHD II and 45% or lower in NYHD IIas assessed according to local methodology by 2-D echocardiography, radionuclide ventriculography, cardiac magnetic resonance imaging, or X-ray contrast ventriculography within 6 months prior to randomisation. For patients treated with beta-blockers or with cardiac resynchronisation, LVEF assessment for eligibility must be performed at least 3 months after stable beta-blocker therapy or device implantation. 5. Screening Hb at least 9.5 g/dL but below or equal to 13.5 g/dL (average of 2 haemoglobin concentrations as measured locally by HemoCue® analyzer; see Section 3.3.5.2 of protocol). 6. Screening ferritin below 100 μg/L, or below 300 μg/L when transferrin saturation (TSAT) is below 20%. 7. Resting blood pressures less than or equal to 160 mm Hg (systolic) and less than or equal to 100 mm Hg (diastolic at the disappearance of sounds, Korotkoff phase V). 8. Adequate veins for repeated blood sampling and i.v. administration of investigational drug. 9. Negative pregnancy test and use of adequate contraceptive methods for women of childbearing potential.
10. Patient must be able to perform the 6 minute walk test according to investigator judgement
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E.4 | Principal exclusion criteria |
1. History of acquired iron overload. 2. Known hypersensitivity to Ferinject®. 3. Known active infection, CRP > 20 mg/L, clinically significant bleeding, active malignancy. 4. Chronic liver disease and/or screening alanine transaminase (ALT) or aspartate transaminase (AST) above three times the upper limit of the normal range. 5. Anaemia due to reasons other than iron deficiency (e.g. haemoglobinopathy). 6. Immunosuppressive therapy or renal dialysis (current or planned within the next 6 months). 7. History of erythropoietin, i.v. or oral iron therapy, and blood transfusion in previous 12 weeks and/or such therapy planned within the next 6 months. 8. Unstable angina pectoris as judged by the investigator, clinically significant uncorrected valvular disease or left ventricular outflow obstruction, obstructive cardiomyopathy, poorly controlled fast atrial fibrillation or flutter, poorly controlled symptomatic brady- or tachyarrhythmias. 9. Acute myocardial infarction or acute coronary syndrome, transient ischaemic attack or stroke within the last 3 months. 10. Coronary-artery bypass graft, percutaneous intervention (e.g. cardiac, cerebrovascular, aortic; diagnostic catheters are allowed) or major surgery, including thoracic and cardiac surgery, within the last 3 months. 11. Known HIV/AIDS. 12. Inability to fully comprehend and/or perform study procedures in the investigator’s opinion. 13. Vitamin B12 and/or serum folate deficiency according to the central laboratory (re-screening is possible after substitution therapy). 14. Pregnancy or lactation. 15. Participation in another clinical trial within previous 30 days and/or anticipated participation in another trial during this study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Self-reported patient global assessment (PGA) score and change in NYHA class from baseline to Week 24 visit after start of investigational drug, taking into account patients who are hospitalised at that time or have died. |
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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 | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 73 |
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 | 18 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 18 |