E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Anaemia following cardiac surgery |
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E.1.1.1 | Medical condition in easily understood language |
Anaemia following cardiac surgery |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 22.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057220 |
E.1.2 | Term | Acute post haemorrhagic anaemia |
E.1.2 | System Organ Class | 100000004851 |
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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 | 10022974 |
E.1.2 | Term | Iron deficiency anemia |
E.1.2 | System Organ Class | 100000004851 |
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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 compare the efficacy of single-, high-dose intravenous iron infusion versus oral iron supplementation for the treatment of anaemia following cardiac surgery. |
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E.2.2 | Secondary objectives of the trial |
To compare single-, high-dose intravenous iron infusion versus oral iron supplementation in the following postoperative outcomes: -Iron deficiency -Red blood cell transfusion requirements -Exercise capacity -Health-related quality of life -Fatigue -Treatment side-effects To perform a cost-effectiveness analysis of intravenous iron supplementation |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients undergoing first-time, non-emergent cardiac surgery 2. Moderate anemia on the first postoperative day (i.e. a haemoglobin concentration of ≥ 5.0 mmol/l [8 g/dl] and < 6.8 mmol/l [11 g/dl]) |
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E.4 | Principal exclusion criteria |
Absolute and relative contraindications to treatment with intravenous iron Treatment with intravenous iron within 4 weeks prior to surgery. Untreated vitamin B12 or folate deficiency. Anticipated inability to perform a six-minute walk test. Women of childbearing potential, pregnant and nursing women. Anticipated postoperative length of stay in the intensive care unit (ICU) > 48 hours. Patients incapable of giving consent personally. Significantly increased risk of non-adherence or loss to follow-up. Active participation in another interventional trial with potential impact on postoperative anaemia or exercise capacity. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of participants who are - neither anemic at 4-week follow-up - nor have received red blood cell transfusion since randomisation. According to WHO criteria, anaemia is defined as a haemoglobin concentration of less than 8.1 mmol/l (13 g/dl) in men and less than 7.4 mmol/l (12 g/dl) in women
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
4 weeks after randomisation (approximately 4 weeks postoperatively) |
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E.5.2 | Secondary end point(s) |
1. Mean change in haemoglobin level from baseline 2. Proportion of participants with a haemoglobin increase ≥ 1.3 mmol/l (≥ 2 g/dL) from baseline 3. Mean haemoglobin level, reticulocyte count, plasma iron, ferritin, transferrin saturation 4. Mean change in haemoglobin level, reticulocyte count, plasma iron, ferritin, transferrin saturation from before surgery 5. Proportion of participants transfused with allogeneic red blood cells after randomisation 6. Six-minute walk distance 7. Health-related quality of life, assessed with the standardized EuroQol Group five dimensions questionnaire (EQ-5D). 8. Fatigue, assessed with the Multidimensional Fatigue Inventory (MFI-20). 9. New York Heart Association (NYHA) functional class. 10. Quality of recovery, assessed with the Quality of Recovery score (QoR-9). 11. Gastrointestinal symptoms. 12. Treatment adherence to oral study drug 13. Cost-effectiveness analysis |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
4 weeks after randomisation (approximately 4 weeks postoperatively) |
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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 | 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 | Yes |
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 | 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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Iron sulfate (Standard therapy of postoperative anaemia: oral iron supplementation) |
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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 | 2 |
E.8.9.1 | In the Member State concerned days | |