E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Coronary or heart valve disease needing cardiac surgery |
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E.1.1.1 | Medical condition in easily understood language |
Coronary or heart valve disease needing cardiac surgery |
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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 | 10068617 |
E.1.2 | Term | Coronary heart disease |
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 | LLT |
E.1.2 | Classification code | 10019316 |
E.1.2 | Term | Heart valve disorders |
E.1.2 | System Organ Class | 100000004849 |
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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 whether pre-operative intravenous iron isomaltoside reduces peri-operative myocardial injury (PMI), as reflected by lower troponin T levels over 72 hours, in patients undergoing coronary artery bypass grafting (CABG) +/- valve surgery.
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E.2.2 | Secondary objectives of the trial |
1. PMI as reflected by creatine kinase (CK)-MB 72 hour AUC 2. Global tissue anaerobic metabolism reflected by lactate 72 hour AUC 3. Renal injury reflected by creatinine and estimated glomerular filtration rate (eGFR) 3 day AUC 4. Hepatic injury reflected by aspartate transaminase (AST) 3 day AUC 5. Inflammatory burden as reflected by C-reactive protein 3 day AUC 6. Iron status and haemoglobin 7. Cardiac function as reflected by LVEF 8. Symptoms as reflected by New York Heart Association and Canadian Cardiovascular Society class. 9. Quality of life as reflected by the European quality of life: 5 dimensions-5 levels and the patient global assessment of clinical status (PGA) scores. 10. Exercise capacity as reflected by 6 minute walk distance 11. Myocardial energetics, redox status and cardioprotective pathways 12. Haemodynamic stability as reflected by inotrope score over 72 hours 13. Length of ITU and total hospital stay 14. Post-op complications 15. Adverse events |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Aged 18 to 89 years • Able to provide written informed consent • Eligible and scheduled for elective on-pump CABG ± valve surgery • Iron deficient (Ferritin<100 µg/L or 100-300 µg/L with TSAT<20%) or iron replete (Ferritin 100-300 µg/L with TSAT 20-40% or Ferritin 300-500 µg/L with TSAT≤40%) • LVEF ≤ 45% or > 45% on echocardiography within the preceding 3 months
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E.4 | Principal exclusion criteria |
• Ferritin > 500 mg/ml • TSAT>40% • Hb > 160 g/L • Hb < 90 g/L and/or needing pre-operative blood transfusion • Conventional iron deficiency anaemia (Ferritin <20 µg /L and Hb <120 g/L) • Pregnant or breast-feeding • Use of erythropoietic or immunosuppressive agents in the 30 days preceding screening and/or unwilling or unable to refrain from their use during the trial • Acute or chronic bleeding • Active infection • Active inflammatory condition (e.g. flare up of SLE, rheumatoid, gout, etc) • Known iron overload or haemochromatosis in patient or first degree relatives. • Prior intolerance to IV iron formulations or any of their excipients • Severe atopic disorders including severe asthma, eczema or any prior anaphylactoid / anaphylactic reaction. • Haemolytic or myelodysplastic anaemia • Enrolment in another clinical trial which might impact FERRIC-CABG
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy analysis will be a comparison of the Troponin T 72 hour area-under-the-curve between all patients who received iron isomaltoside versus all patients who received placebo. This will be done with an unpaired Student t-test or Mann-Whitney U-test depending on data distribution (normal vs non-normal distribution). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Troponin T levels will be taken at baseline prior to CABG, and at 6, 12, 24, 48, and 72 hours post surgery (after coming off bypass). |
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E.5.2 | Secondary end point(s) |
1. CK-MB 72 hour AUC 2. Lactate 72 hour AUC 3. Creatinine 3 day AUC 4. eGFR 3 day AUC 5. AST 3 day AUC 6. CRP 3 day AUC 7. Iron status (ferritin, transferrin saturation [TSAT], serum iron, and total iron binding capacity [TIBC]) on day -1 or 0 prior to induction for surgery 8. Hb on day -1 or 0 pre-op 9. Inotrope score over 72 hours 10. LVEF post-op 11. NYHA class at post-op clinic 12. CCS class at post-op clinic 13. PGA score at post-op clinic 14. EQ-5D-5L score at post-op clinic 15. Length of ITU stay 16. Length of hospital stay 17. Myocardial biopsy analyses (e.g. myocardial oxygen consumption, antioxidants, redox status, cardioprotective pathways) 18. 6MWD post-op 19. Number and incidence of adverse events and post-op complications
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
At baseline and on discharge or at 4-12 week post-op outpatient clinic unless stated above. |
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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) | 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 | 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 | 2 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 31 |