Effect of Ferric Carboxymaltose on Exercise Capacity After Kidney Transplantation (EFFECT-KTx)

University Medical Center Groningen (UMCG)

Status and phase: Completed; Phase 3

Conditions: Iron-deficiency; Transplant-Related Disorder

Treatments: Drug: Ferric carboxymaltose; Drug: Sodium chloride

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03769441

201800450

Details and patient eligibility

About

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.

Full 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.

Enrollment: 148 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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148 participants in 2 patient groups, including a placebo group

Ferric(III) carboxymaltose

Active Comparator group

Description:

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.

Treatment:

Drug: Ferric carboxymaltose

Placebo

Placebo Comparator group

Description:

The placebo-controlled group will receive four dosages of 250 mL of NaCl 0.9% solution with interval periods of six weeks.

Treatment:

Drug: Sodium chloride