Effect of Ferric Carboxymaltose on Exercise Capacity After Kidney Transplantation

University Medical Center Groningen148 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

148

Conditions

Iron-deficiency Transplant-Related Disorder

Interventions

Ferric carboxymaltoseDRUG

Four intravenous dosages of ferric(III) carboxymaltose

Sodium chlorideDRUG

Four intravenous dosages of sodiumchloride

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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

Locations (2)

University Medical Center Groningen

Groningen, Netherlands

University Medical Center Utrecht

Utrecht, Netherlands

Outcomes

Primary Outcomes

Exercise tolerance

The between-group difference in change in exercise tolerance quantified by the six-minute walk test (6MWT)

Time frame: 24 weeks

Secondary Outcomes

Hemoglobin level

The between-group difference in change in hemoglobin level

Time frame: 24 weeks

Iron status

The between-group difference in change in iron parameters (plasma iron, ferritin, transferrin saturation)

Time frame: 24 weeks

Cardiac function

The between-group difference in change in cardiac structure, function and strain, analysed with a transthoracic echocardiography

Time frame: 24 weeks

Muscle strength 1

The between-group difference in change in muscle strength measured by the 'Five-Times-Sit-to-Stand-test (FTSTS)

Time frame: 24 weeks

Muscle strength 2

The between-group difference in change in muscle strength measured by the timed-up-and-Go test (TUG)

Time frame: 24 weeks

Muscle strength 3

The between-group difference in change in muscle strength measured by handgrip dynamometry

Time frame: 24 weeks

Muscle mass

The between-group difference in change in muscle mass assessed using 24-hour urinary creatinine excretion

Time frame: 24 weeks

Data from ClinicalTrials.gov

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Phosphate level

The between-group difference in change in phosphate level

Time frame: 24 weeks

Calcium level

The between-group difference in change in calcium level

Time frame: 24 weeks

Vitamin D status

The between-group difference in change in vitamin D level

Time frame: 24 weeks

Parathyroid hormone

The between-group difference in change in parathyroid hormone level level

Time frame: 24 weeks

FGF23

The between-group difference in change in FGF23 level

Time frame: 24 weeks

Intestinal microbiota

The between-group difference in change in intestinal microbiota

Time frame: 24 weeks

Incidence of any infection

The between-group difference in incidence of infections

Time frame: 24 weeks

Incidence of hospitalisation

The between-group difference in incidence of hospitalisation

Time frame: 24 weeks

Incidence of cardiac events

The between-group difference in incidence of cardiac events

Time frame: 24 weeks

Incidence of graft failure

The between-group difference in incidence of graft failure

Time frame: 24 weeks

Lymphocyte production of cytokines

The between-group difference in lymphocyte cytokine espression (measured with facs)

Time frame: 24 weeks

Lymphocyte production of immunoglobulins

The between-group difference in lymphocyte IgG production (measured with ELISA)

Time frame: 24 weeks

Lymphocyte proliferation rate

The between-group difference in lymphocyte proliferation rate (assessed with FACS)

Time frame: 24 weeks

B-lymphocyte differentiation rate

The between-group difference in B-lymphocyte plasma cell formation (assessed with Facs)

Time frame: 24 weeks

Cognitive performance (memory span)

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)

Time frame: 24 weeks

Cognitive performance (verbal memory)

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)

Time frame: 24 weeks

Cognitive performance (semantic memory)

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)

Time frame: 24 weeks

Cognitive performance (processing speed)

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)

Time frame: 24 weeks

Cognitive performance (visuomotor and mental speed)

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)

Time frame: 24 weeks

Cognitive performance (cognitive flexibility)

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)

Time frame: 24 weeks

Cognitive performance (executive control)

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)

Time frame: 24 weeks

Cognitive performance (working memory)

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)

Time frame: 24 weeks

Plasma creatinine

The between-group difference in change in plasma creatinine

Time frame: 24 weeks

Quality of Life (health)

The between-group difference in change in quality of life quantified with SF36 questionnaire. A higher score means a better outcome.

Time frame: 24 weeks

Quality of Life (subjective fatigue)

The between-group difference in change in quality of life quantified with the Dutch Checklist individual Strength). A higher score means worse fatigue.

Time frame: 24 weeks

Quality of Life (long-lasting fatigue)

The between-group difference in change in quality of life quantified with the Dutch Multifactor Fatigue Scale). A higher score means worse fatigue.

Time frame: 24 weeks

Quality of Life (overall)

The between-group difference in change in quality of life quantified with EuroQol-5D-5L

Time frame: 24 weeks

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination IgG response

The between-group difference in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) specific antibody titre after vaccination.

Time frame: 12 months

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination T-lymphocyte response

The between-group difference in severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) specif T-lymphocyte response after vaccination.

Time frame: 12 months

Gastro-intestinal symptoms

The between-group difference in change in gastro-intestinal symptoms assessed with the gastrointestinal symptom rating scale.

Time frame: 24 weeks

Hepatic injury

The between-group difference in change in plasma hepatic enzyme levels (aspartate transaminase and alanine transaminase)

Time frame: 24 weeks

Restless legs

The between-group difference in prevalence of restless legs symptoms before and after treatment

Time frame: 24 weeks

Kidney graft rejection and injury

The between-group difference in change in urine kidney injury marker levels

Time frame: 24 weeks