Clinical trial NCT03769441: Effect of Ferric Carboxymaltose on Exercise Capacity After Kidney Transplantation
Official title: Effect of Ferric Carboxymaltose on Exercise Capacity After Kidney Transplantation: a Multicenter Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Iron-deficiency
Transplant-Related Disorder
Keywords: Renal Transplantation
Kidney Transplantation
Iron Deficiency
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
Collaborators: name: Dutch Kidney Foundation
name: Vifor Fresenius Medical Care Renal Pharma
First posted: 2018-12-07
Enrollment: 148
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study is designed as a 24 week, multicentre, randomized placebo-controlled clinical trial with two parallel arms to investigate the effect of ferric(III) carboxymaltose on exercise tolerance, cardiac function, skeletal muscle function, quality of life, the gut microbiota and on the immune system, to be performed at the University Medical Center Groningen (UMCG) and the Erasmus MC, University Medical Center Rotterdam.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Exercise tolerance
timeFrame: 24 weeks
Secondary outcomes:
measure: Hemoglobin level
timeFrame: 24 weeks
measure: Iron status
timeFrame: 24 weeks
measure: Cardiac function
timeFrame: 24 weeks
measure: Muscle strength 1
timeFrame: 24 weeks
measure: Muscle strength 2
timeFrame: 24 weeks
measure: Muscle strength 3
timeFrame: 24 weeks
measure: Muscle mass
timeFrame: 24 weeks
measure: Phosphate level
timeFrame: 24 weeks
measure: Calcium level
timeFrame: 24 weeks
measure: Vitamin D status
timeFrame: 24 weeks
measure: Parathyroid hormone
timeFrame: 24 weeks
measure: FGF23
timeFrame: 24 weeks
measure: Intestinal microbiota
timeFrame: 24 weeks
measure: Incidence of any infection
timeFrame: 24 weeks
measure: Incidence of hospitalisation
timeFrame: 24 weeks
measure: Incidence of cardiac events
timeFrame: 24 weeks
measure: Incidence of graft failure
timeFrame: 24 weeks
measure: Lymphocyte production of cytokines
timeFrame: 24 weeks
measure: Lymphocyte production of immunoglobulins
timeFrame: 24 weeks
measure: Lymphocyte proliferation rate
timeFrame: 24 weeks
measure: B-lymphocyte differentiation rate
timeFrame: 24 weeks
measure: Cognitive performance (memory span)
timeFrame: 24 weeks
measure: Cognitive performance (verbal memory)
timeFrame: 24 weeks
measure: Cognitive performance (semantic memory)
timeFrame: 24 weeks
measure: Cognitive performance (processing speed)
timeFrame: 24 weeks
measure: Cognitive performance (visuomotor and mental speed)
timeFrame: 24 weeks
measure: Cognitive performance (cognitive flexibility)
timeFrame: 24 weeks
measure: Cognitive performance (executive control)
timeFrame: 24 weeks
measure: Cognitive performance (working memory)
timeFrame: 24 weeks
measure: Plasma creatinine
timeFrame: 24 weeks
measure: Quality of Life (health)
timeFrame: 24 weeks
measure: Quality of Life (subjective fatigue)
timeFrame: 24 weeks
measure: Quality of Life (long-lasting fatigue)
timeFrame: 24 weeks
measure: Quality of Life (overall)
timeFrame: 24 weeks
measure: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination IgG response
timeFrame: 12 months
measure: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccination T-lymphocyte response
timeFrame: 12 months
measure: Gastro-intestinal symptoms
timeFrame: 24 weeks
measure: Hepatic injury
timeFrame: 24 weeks
measure: Restless legs
timeFrame: 24 weeks
measure: Kidney graft rejection and injury
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: University Medical Center Groningen
name: Martin de Borst, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References: