Multicentre prospective double blinded randomised controlled trial of the effect of intravenous iron supplementation and exercise training in Iron deficient, but not anaemic, patients with Chronic Kidney Disease on exercise capacity, physical function, fatigue and skeletal muscle metabolism. - Iron and Muscle

INTERVENTION: Trade Name: Ferrinject Product Name: Ferrinject Pharmaceutical Form: Injection INN or Proposed INN: Ferric carboxymaltose CAS Number: 009007‐72‐1 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 8.33‐ Pharmaceutical form of the placebo: Solution for injection/infusion Route of administration of the placebo: Intravenous use CONDITION: Iron deficiency in stage 3‐4 CKD ; MedDRA version: 20.0 Level: PT Classification code 10064848 Term: Chronic kidney disease System Organ Class: 10038359 ‐ Renal and urinary disorders ; MedDRA version: 20.0 Level: LLT Classification code 10066763 Term: Chronic iron deficiency anaemia System Organ Class: 100000004851 Therapeutic area: Diseases [C] ‐ Blood and lymphatic diseases [C15] PRIMARY OUTCOME: ; Secondary Objective: 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.; Main Objective: 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. Primary end point(s): The 6‐minute Walking distance test (in metres) ‐ An exercise capacity test. Timepoint(s) of evaluation of this end point: Baseline, 4 weeks and 12 weeks. SECONDARY OUTCOME: ; 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; 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. 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 Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30