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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E.1.1.1 | Medical condition in easily understood language |
Iron deficiency in patients with chronic heart failure |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008908 |
E.1.2 | Term | Chronic heart failure |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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 |
1. To evaluate the efficacy of intravenous ferric carboxymaltose compared to usual care on exercise capacity. |
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E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy of IV FCM compared to usual care on biomarkers for iron deficiency (ID), cardiac biomarkers, New York Heart Association (NYHA) functional class, patient global assessment (PGA), quality of life (QoL), renal function, cardiac function as assessed by echocardiography (ECHO) and iron requirements in iron-deficient chronic heart failure (CHF) subjects.
2. To evaluate the safety of intravenous ferric carboxymaltose over the treatment period. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Iron deficient subjects with stable chronic heart failure (CHF) (NYHA II-III) on optimal background therapy for CHF
2. Reduced exercise capacity
3. Reduced left ventricular ejection fraction
4. At least 18 years of age and with written informed consent prior to any study specific procedures.
|
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E.4 | Principal exclusion criteria |
1. Erythropoietin stimulating agent (ESA) use, IV iron therapy, and/or blood transfusion in previous 6 weeks prior to randomisation
2. Exercise training program(s) in the 3 months prior to screening or planned in the next 6 months
3. Chronic liver disease and/or elevated liver enzymes
4. Vitamin B12 and/or serum folate deficiency that requires treatment
5. Subject is not using adequate contraceptive precautions during the study
6. No other significant cardiac or general disorder that would compromise participation in the study.
7. Subjects with body weight <35 kg |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in peak VO2 (mL/kg/min) from baseline to Week 24 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Change in peak VO2 (mL/kg/min) from baseline to Week 12
2. Change in minute ventilation-carbon dioxide production slope from baseline to Weeks 12 and 24
3. Changes from baseline to Weeks 6, 12 and 24 in:
− Key laboratory and iron parameters
− Cardiac biomarkers (including BNP and NT-proBNP)
− NYHA
− PGA
− QoL (Kansas City cardiomyopathy questionnaire (KCCQ) and European quality of life 5D questionnaire (EQ-5D))
- ECHO measurements
4. Cumulative iron requirements and number of iron administrations over the study period
5. Percentage of subjects meeting key safety endpoint defined as time to:
− Death
− (First) hospitalisation for worsening heart failure
− Heart transplantation |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Week 12
2. Week 12 & Week 24
3. Week 6, Week 12, & Week 24
4. End of Study
5. End of Study |
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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 | 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) | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Standard of care. IV iron not permitted |
|
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
| 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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
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 | No |
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 |
Australia |
Belgium |
France |
Germany |
Italy |
Netherlands |
Poland |
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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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Last visit of the last subject |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |