Effect of Ferric Carboxymaltose on Exercise Capacity After Kidney Transplantation
- Conditions
- Iron-deficiencyTransplant-Related Disorder
- Interventions
- Registration Number
- NCT03769441
- Lead Sponsor
- University Medical Center Groningen
- Brief Summary
Iron deficiency is common in kidney transplant recipients and is associated with impaired exercise tolerance and an unfavourable prognosis.
This multicentre double-blind, placebo-controlled randomized controlled clinical trial will allow the investigators to analyse the effects of intravenous iron correction with ferric(III) carboxymaltose on exercise tolerance and other parameters, in comparison to a placebo.
- Detailed Description
Rationale: Iron deficiency is common in kidney transplant recipients. The presence of iron deficiency is associated with an unfavourable prognosis in these patients. In patients with heart failure and iron deficiency, treatment with intravenous iron improved exercise capacity and quality of life. Whether such beneficial effects may also occur in kidney transplant recipients is unknown.
Objective: Our main objective is to address whether correction of iron deficiency with ferric(III) carboxymaltose improves exercise tolerance and quality of life in iron-deficient kidney-transplant recipients.
Study design: A multicentre double-blind, placebo-controlled randomized controlled clinical trial will be performed to compare the effects of ferric(III) carboxymaltose with placebo.
Study population: 158 iron-deficient kidney transplant recipients. The intervention arm will receive 10 mL of ferric(III) carboxymaltose (50 mg Fe3/mL, intravenously) every six weeks, with a total of four dosages. The control arm receives an intravenous placebo solution (saline).
Main study parameters/endpoints: The primary endpoint is the distance walked in six minutes, as quantified by the six-minute-walking-test at the end of follow-up.
The investigators expect that iron-deficient kidney transplant recipients will benefit from ferric(III) carboxymaltose treatment as a result of an improvement in exercise tolerance and general wellbeing.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 148
- Kidney transplant recipient
- Iron deficiency, defined by a ferritin level of ≤100 ug/L, or 100-299 ug/L combined with a transferrin saturation of ≤20%
- At least six months after transplantation at baseline
- Age ≥18 years
- Ability to comply with the study protocol
- Informed consent
- Intolerance to any intravenous iron solution
- Severe anemia (Hb <10.5 g/dL, <6.5 mmol/L), microcytic anemia (MCV <80 fl) or progressive anemia (˃3.2 g/dL per month decline for two months or more)
- A positive feces occult blood test or otherwise demonstrated gastrointestinal, or urogenital, blood loss
- Blood transfusion in the past six weeks
- Polycythemia (Hb >15.3 g/dL, 9.5 mmol/L)
- Estimated glomerular filtration rate (eGFR) of ≤ 30 ml/min per 1.73 m2
- History of haemochromatosis
- Unstable angina or myocardial infarction during the previous month
- Disability to walk
- Severe hypophosphatemia in the month before baseline (serum phosphate <0.35 mmol/L)
- Pregnancy or inability to take adequate contraceptive measures when at childbearing age (women)
- Any signs of an active systemic infection
- Participation in another interventional study
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Ferric(III) carboxymaltose Ferric carboxymaltose The intervention group will be treated with four dosages of 500 mg iron in the form of 10 mL ferric(III) carboxymaltose dissolved in 240 mL of NaCl 0.9%, with interval periods of six weeks. Placebo Sodium chloride The placebo-controlled group will receive four dosages of 250 mL of NaCl 0.9% solution with interval periods of six weeks.
- Primary Outcome Measures
Name Time Method Exercise tolerance 24 weeks The between-group difference in change in exercise tolerance quantified by the six-minute walk test (6MWT)
- Secondary Outcome Measures
Name Time Method Cognitive performance (semantic memory) 24 weeks The between-group difference in change in cognitive performance quantified with neuropsychological testing (Word Fluency Test, minimum value 0, no maximum value, a higher score means a better outcome)
Plasma creatinine 24 weeks The between-group difference in change in plasma creatinine
Hemoglobin level 24 weeks The between-group difference in change in hemoglobin level
Muscle mass 24 weeks The between-group difference in change in muscle mass assessed using 24-hour urinary creatinine excretion
Phosphate level 24 weeks The between-group difference in change in phosphate level
Parathyroid hormone 24 weeks The between-group difference in change in parathyroid hormone level level
FGF23 24 weeks The between-group difference in change in FGF23 level
Incidence of hospitalisation 24 weeks The between-group difference in incidence of hospitalisation
Incidence of cardiac events 24 weeks The between-group difference in incidence of cardiac events
Lymphocyte proliferation rate 24 weeks The between-group difference in lymphocyte proliferation rate (assessed with FACS)
Iron status 24 weeks The between-group difference in change in iron parameters (plasma iron, ferritin, transferrin saturation)
Muscle strength 3 24 weeks The between-group difference in change in muscle strength measured by handgrip dynamometry
Calcium level 24 weeks The between-group difference in change in calcium level
Cognitive performance (memory span) 24 weeks The between-group difference in change in cognitive performance quantified with neuropsychological testing (Digit Span Forward Test, minimum value 0, maximum value 9, a higher score means a better outcome)
Quality of Life (subjective fatigue) 24 weeks The between-group difference in change in quality of life quantified with the Dutch Checklist individual Strength). A higher score means worse fatigue.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination T-lymphocyte response 12 months The between-group difference in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) specif T-lymphocyte response after vaccination.
Gastro-intestinal symptoms 24 weeks The between-group difference in change in gastro-intestinal symptoms assessed with the gastrointestinal symptom rating scale.
Cardiac function 24 weeks The between-group difference in change in cardiac structure, function and strain, analysed with a transthoracic echocardiography
Muscle strength 1 24 weeks The between-group difference in change in muscle strength measured by the 'Five-Times-Sit-to-Stand-test (FTSTS)
Vitamin D status 24 weeks The between-group difference in change in vitamin D level
Intestinal microbiota 24 weeks The between-group difference in change in intestinal microbiota
Incidence of any infection 24 weeks The between-group difference in incidence of infections
Incidence of graft failure 24 weeks The between-group difference in incidence of graft failure
Lymphocyte production of cytokines 24 weeks The between-group difference in lymphocyte cytokine espression (measured with facs)
Lymphocyte production of immunoglobulins 24 weeks The between-group difference in lymphocyte IgG production (measured with ELISA)
B-lymphocyte differentiation rate 24 weeks The between-group difference in B-lymphocyte plasma cell formation (assessed with Facs)
Cognitive performance (verbal memory) 24 weeks The between-group difference in change in cognitive performance quantified with neuropsychological testing (15 word test, minimum value 0, maximum value 75, a higher score means a better outcome)
Cognitive performance (processing speed) 24 weeks The between-group difference in change in cognitive performance quantified with neuropsychological testing (symbol digit modalities test, minimum value 0, maximum value 110, a higher score means a better outcome)
Cognitive performance (executive control) 24 weeks The between-group difference in change in cognitive performance quantified with neuropsychological testing (Controlled Oral Word Association Test, minimum score 1, no maximum score, a higher score means a better outcome)
Cognitive performance (working memory) 24 weeks The between-group difference in change in cognitive performance quantified with neuropsychological testing (Digit Span Backward, minimum score 0, maximum score 8, a higher score means a better outcome)
Muscle strength 2 24 weeks The between-group difference in change in muscle strength measured by the timed-up-and-Go test (TUG)
Cognitive performance (visuomotor and mental speed) 24 weeks The between-group difference in change in cognitive performance quantified with neuropsychological testing (Trail Making Test A, minimum value 1, no maximum value, a lower score means a better outcome)
Cognitive performance (cognitive flexibility) 24 weeks The between-group difference in change in cognitive performance quantified with neuropsychological testing (Trail Making Test B, minimum value 1, no maximum value, a lower score means a better outcome)
Quality of Life (health) 24 weeks The between-group difference in change in quality of life quantified with SF36 questionnaire. A higher score means a better outcome.
Quality of Life (long-lasting fatigue) 24 weeks The between-group difference in change in quality of life quantified with the Dutch Multifactor Fatigue Scale). A higher score means worse fatigue.
Quality of Life (overall) 24 weeks The between-group difference in change in quality of life quantified with EuroQol-5D-5L
Hepatic injury 24 weeks The between-group difference in change in plasma hepatic enzyme levels (aspartate transaminase and alanine transaminase)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination IgG response 12 months The between-group difference in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) specific antibody titre after vaccination.
Restless legs 24 weeks The between-group difference in prevalence of restless legs symptoms before and after treatment
Kidney graft rejection and injury 24 weeks The between-group difference in change in urine kidney injury marker levels
Trial Locations
- Locations (2)
University Medical Center Groningen
🇳🇱Groningen, Netherlands
University Medical Center Utrecht
🇳🇱Utrecht, Netherlands