E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Iron deficiency in stage 3-4 CKD |
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E.1.1.1 | Medical condition in easily understood language |
Shortage iron in the context of non-dialysis patients with chronic kidney disease |
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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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064848 |
E.1.2 | Term | Chronic kidney disease |
E.1.2 | System Organ Class | 10038359 - Renal and urinary disorders |
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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 | 10066763 |
E.1.2 | Term | Chronic iron deficiency anaemia |
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 assess the effect of intravenous iron on exercise capacity, as assessed by 6-minute walking distance, with and without exercise training in patients with chronic kidney disease and iron deficiency, but without anaemia. |
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E.2.2 | Secondary objectives of the trial |
1) To assess physical capacity, quality-of-life, and skeletal muscle metabolism in patients with chronic kidney disease and iron and deficiency, but without anaemia. 2) To determine if iron repletion enhances the effect of an 8-week exercise programme when compared to placebo treatment.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Patients with established CKD (Stages 3-4) not on dialysis • Resting BP ≤ 160/95mmHg • Men and women aged 18 - 80 years • Serum ferritin level less than 100µg/L AND/OR transferrin saturation ≤20% • Haemoglobin 110 – 150 g/L • Written informed consent
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E.4 | Principal exclusion criteria |
•Pregnancy or breast feeding (Female patients of child bearing age will be asked if there is any possibility they may be pregnant. This is standard of care and no pregnancy test will be requested unless there is doubt about this. IV iron is given to many pregnant patients in standard treatment and there is no evidence of harm to mother or foetus). •Weight < 50kg •Known allergy to iron therapy •Haemochromatosis, porphyria cutanea tarda or history of acquired iron overload •Intravenous iron within previous 6 weeks •CRP > 50 mg/L •Serum phosphate < 0.7 mmol/L. •Active infection •Current therapy with ESAs •Uncontrolled atrial fibrillation •Use of anticoagulants in those under consideration for muscle biopsy •Unstable angina or heart attack within the last year •Presence of solid organ cancer •Known haemoglobinopathy, myelodysplasia, or myeloma •Patients with peripheral vascular or musculoskeletal disease, who the investigator deems unable to carry out the 6MWT. •Known severe aortic stenosis and pacemaker in-situ •History of severe atopy •Severe liver disease with serum transaminases > x3 upper limit of normal range according to local laboratory values. •Severe lung disease with FEV1 known to be <50% predicted in last year •Known heart failure with a left ventricular ejection fraction <45% in last year •Any other health condition considered by the local Principal Investigator in which IV iron will be contraindicated. •Insufficient understanding of the trial
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E.5 End points |
E.5.1 | Primary end point(s) |
The 6-minute Walking distance test (in metres) - An exercise capacity test. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline, 4 weeks and 12 weeks. |
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E.5.2 | Secondary end point(s) |
•Iron status (Ferritin, TSAT) and haemoglobin •Renal function (urea, creatinine, estimated glomerular filtration rate) •VO2 peak test (in a sub-set of participants) •Isokinetic dynamometry (muscle strength) •Chalder Fatigue Questionnaire -- physical and mental fatigue •Functional capacity (sit-to-stand 60 to assess lower limb function) •Quality of life (KDQOL-36) •Skeletal muscle phosphocreatine recovery halftime (PCr t1/2) on MRI spectroscopy (n=40 patients at baseline and 4 weeks) •Muscle metabolism •Patient recruitment and retention •Qualitative exploration of participant experience •The Work and Social Adjustment Scale (WSAS) •Adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All at baseline, 4 weeks and 12 weeks except for muscle metabolism which will be at baseline and 4 weeks. |
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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 | 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
| 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 | 7 |
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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The end of the trial will be defined as date of database lock. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 1 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 1 |